souvenir programme

www.mshaema.com

SCIENTIFIC MEETING 2022

thV i r t u a l C o n f e r e n c eV i r t u a l C o n f e r e n c e

Dates:

Conference Workshop Venue :Hospital CanselorTuanku Muhriz (HCTM)

CELL THERAPYCELL THERAPYConference Theme:

Co-Organised with Pusat Terapi Sel, Hospital Canselor Tuanku Muhriz (HCTM)

SOUVENIRPROGRAMME

9th – 11th August 2022*There will be hands-on workshop on the 9th August 2022 but with limited capacity. First come, first serve

President Prof Dr. Gan Gin Gin

Vice President Dr. Haris Abdul Rahman

Hon. Secretary Dr. Veena Selvaratnam

Hon. Treasurer

Council Member

Dr. Sharifah Shahnaz Alkudsi

Dato’ Dr. Goh Ai SimDr. Tan Sen MuiProf Dr. Bee Ping ChongProf Dr. Azlan HusinDr. Gan Ee LengDr. Abu Dzarr Abdullah

19th Malaysian Society Of Haematology Scientific Meeting 20222

Dear Friends and Colleagues,

It is my great pleasure to welcome you to the19th Annual Scientific Meeting 2022 organized by the Malaysian Society of Haematology. Under the able leadership of Professor Dr S. Fadilah Abdul Wahid and her organizing committee, we have an exciting scientific program installed for everyone.

This year’s theme on Cell Based Therapies is a flourishing field which has experienced exponential growth in both clinical use and research, gaining recognition and offering hope. However, there are still many challenges which limit its use, including accessibility and expertise. Thus, it is apt

that we are provided the opportunity to learn and share our experiences and challenges with well-known keynote speakers invited by the organizing committee. The society hopes to provide effective platform for our members and friends for self-improvement and at the same time, have fun and make new friends, albeit virtually.

I would like to once again record my deepest appreciation to Professor S Fadilah Abdul Wahid and her team who have worked tireless to make this meeting successful. Similarly, I like to thank our generous industry sponsors and partners who see the importance of continuous medical education.

Lastly, I hope you will find this meeting stimulating and rewarding.

Professor Dr. Gan Gin Gin PresidentMalaysian Society of Haematology

Welcome Message from the President of theMalaysian Society of Haematology (MSH)

Council Members 2022/2023

souvenir programme book 3

Welcome Message from the 19th MSH ASM 2022 Organising Chairperson

On behalf of the MSH 2022 organising committee, it is with great pleasure and honour that I welcome all of you to the 19th Malaysian Society of Haematology Annual Scientific Meeting on both virtual and physical platforms. The conference starts virtually on 9th August 2022 along with hands-on workshop, and continues with the rest of the virtual programme from 10th-11th August 2022. Although we are thankful that the current Covid-19 situation is slightly more manageable now, precautions are still essential and therefore I hope our online sessions will be as beneficial to you as much as possible.

The focus of this year’s exciting and thought-provoking meeting is Cell Based Therapies: The New Frontier In Personalized And Targeted Therapy.

Haematological cancer treatment has evolved immensely from conventional cytotoxic chemotherapy, monoclonal based immunotherapy to cell-based therapies. In parallel, the field of cellular therapy has progressed rapidly with development of novel therapeutic modalities that include a wide spectrum of products. These include, engineered T-cell receptor (TCR), chimeric antigen receptor (CAR)-T cells, dendritic cells (DC), cytotoxic T lymphocytes (CTLs), natural killer (NK) cells, and others that were primarily developed as a curative approach for highly resistant cancers.

Additionally, recent data from both fundamental and translational research encompassing haematopoietic and mesenchymal stem cells has allowed for innovative therapeutic applications to also benefit non-haematological malignancies and degenerative or ageing disorders.

The scientific programme has been designed to cover many aspects of cutting-edge technologies surrounding cell-based therapy ranging from precision diagnostics to measurable residual disease surveillance especially in the era of multi-color flow cytometric immunophenotyping and translational molecular haematology. These exciting and highly educational content will also be covered in the pre-conference workshop to provide hands on exposure and opportunity to our members.

We hope that this conference will increase our understanding of the progress made in the field of cellular immunotherapies and will serve as an inspiration for future research efforts.

Despite the numerous challenges encountered in moving the field of cellular therapy forward, the success achieved thus far is exciting and promising for a paradigm shift in the years to come in particular for the treatment of haematological malignancies. Researchers and clinicians from around the globe need to work together to advance the field of cell-based therapies toward curative approaches for highly resistant cancers.

I wish to take this opportunity to thank the committee members for the excellent effort and I wish all participants a valuable and enjoyable meeting.

Stay safe.

With best wishes,Professor Dr. S Fadilah Abdul WahidOrganising Chairperson 19th MSH Annual Scientific Meeting 2022

Chairperson Prof. Dr. S Fadilah Abdul Wahid

Co Chairperson Assoc. Prof. Dr. Nurasyikin Yusof

Treasurer Dr. Sivakumar Palaniappan

Scientific Committee Prof. Dr. S Fadilah Abdul WahidDr. Muhd Zanapiah ZakariaDr. Goh Kim YenDr. Jay Suriar RajasuriarAssoc. Prof. Dr. Azlan Husin Prof. Dr. Raja Zahratul Azma Raja SabudinAssoc. Prof. Dr. Wan Fariza Wan JamaludinDr Azizan Sharif

Sponsorship Committee Dr. Nor Saaidah Kamal Rodin SN Seery Zaliza Azura Zaider

Event Committee SN Noraimy AbdullahSn Norfazana OmarKhairul Azaham

Website / Media Committee Nor Azimah IsmailNoralisa Abdul Karim

Abstract & Poster Committee Assoc. Prof. Dr. Rafeah TumianDr. Ezalia EsaDr. Wint Wint Thu NyuntMohd Razif Mohd IdrisAssoc. Prof. Dr. Suria Abdul AzizDr Siti Shahrum Muhamed SaidDr Azlinda Abu Bakar

Workshop Committee Assoc. Prof. Dr. Nurasyikin YusofMuhammad Zarul Helmi AzmiNorrulhuda IbrahimSN Salbiah Razak

Quiz Committee Assoc. Prof. Dr. Asral Wirda Ahmad AsnawiDr. Lau Ngee Siang

Publication Committee Dr. Anisah Farhana SahrirNor Azimah binti Ismail


19th MSH ASM 2022 Organising Committee

Opening Ceremony “19th Malaysian Society of Haematology Scientific Meeting 2022”

Dewan Serbaguna, Blok Tambahan, Kompleks Pendidikan Perubatan Canselor Tuanku Ja’afar, Hospital Canselor Tuanku Muhriz, UKM

Time (GMT+8) Program

0830 Arrival of Guests, Participants

0855 Arrival of VVIPs President of Malaysian Society of Haematology Dean of Faculty of Medicine (UKM) Director of Hospital Canselor Tuanku Muhriz Pro Vice Chancellor (Kuala Lumpur Campus) Vice Chancellor of Universiti Kebangsaan Malaysia (UKM) Deputy Minister of Health Malaysia I

0900 Singing of “NegaraKu” & “Varsiti Kita”

Prayer Recitation

Welcoming Speech by Prof. Dr. Gan Gin Gin

President of Malaysian Society of Haematology

Speech by YBhg. Prof. Dato' Gs. Ts. Dr. Mohd Ekhwan Hj. Toriman

Vice Chancellor of Universiti Kebangsaan Malaysia

Opening Speech by YB. Dato' Dr. Hj. Noor Azmi Ghazali Deputy Minister of Health Malaysia I

Opening Gimmick

Giving of Token of Appreciation

Video Presentation

Photo Session

Press conference

Refreshment

1030 End of Ceremony



Faculty

Professor Dr Mohamad Mohty

Saint -Antoine Hospital, Sorbonne University, Paris,

France

Professor Dr Erica WoodMonash University, Melbourne,

Australia

Professor Dr Martin Griesshammer

Johannes-Wesling Clinic Minden, Minden, Germany

Professor Dr Xiao-Jun Huang

Peking University People’s Hospital & Institute of

Hematology, Beijing, China

Professor Dr Cameron Turtle

Fred Hutchinson Cancer Research Center, Washington,

United States

Professor Dr John MooreSt. Vincent’s Health Network,

Sydney, Australia

Professor Dr Renato Bassan

Ospedale dell’Angelo, Mestre-Venezia, Venice, Italy

Associate Professor Dr Elizabeth Tegg

ICPMR-NSWHP Westmead/University of Sydney, Sydney,

Australia

Professor Dr Christopher Ward

Royal North Shore Hospital, Sydney, Australia

Professor Dr Kwong Yok LamQueen Mary Hospital,

Hong Kong

Professor Dr Roopen Arya

King’s College Hospital, London, United Kingdom

Associate Professor Dr Koh Liang Piu

National University Cancer Institute, Singapore

Professor Dr Constantine Tam

St Vincent’s Hospital, Melbourne, Australia

Professor Dr Matthew J MatasarMemorial Sloan Kettering Cancer Centre. New York,

United States

Professor Dr Sylvie Freeman

University of Birmingham, Birmingham, United Kingdom

Associate Professor Dr Nada Hamad

Kinghorn Cancer Centre, New South Wales, Australia


Faculty

Associate Professor Dr Naval Daver

MD Anderson Cancer Center, Texas, United States

Dr Chen YunxinSingHealth Duke-NUS Blood Cancer Centre, Singapore

Dr Ng Chin HinGleneagles Hospital Singapore,

Singapore

Emeritus Professor Dr Cheong Soon Keng

Universiti Tunku Abdul Rahman, Kuala Lumpur, Malaysia

Associate Professor Dr Peter Mollee

Princess Alexandra Hospital Amyloidosis Centre, Queensland,

Australia

Dr Colin Phipps DiongParkway Cancer Centre,

Singapore

Dr Daryl Tan Chen LungMount Elizabeth Novena

Specialist Centre, Singapore

Dr Rajat BhattacharyyaKK Women’s and Children’s

Hospital, Singapore

Professor Dr S Fadilah Abdul Wahid

Pusat Terapi Sel-UKM, Kuala Lumpur, Malaysia

Assistant Professor Dr Francesca Lim

Singapore General Hospital, Singapore

Dr Drew ProvanThe Royal London Hospital, London, United Kingdom

Dr Robin GasiorowskiMacquarie University, Sydney,

Australia

Professor Dr Bee Ping Chong

University of Malaya Medical Centre, Kuala Lumpur, Malaysia

Dr Anna SuredaInstitut Català d’Oncologia-Hospitalet, Barcelona, Spain

Dr Kenichiro HasumiICVS Tokyo Clinic, Tokyo, Japan

Ms Julija SipaviciusRoyal North Shore Hospital,

Sydney, Australia


Professor Dr Noraidah Masir

Hospital Canselor Tuanku Muhriz, Kuala Lumpur, Malaysia

Professor Dr Raja Zahratul Azma Raja

SabudinHospital Canselor Tuanku Muhriz,

Kuala Lumpur, Malaysia

Associate Professor Ir Ts Dr Mohd Ridzuan

AhmadUniversiti Teknologi Malaysia,

Johor, Malaysia

Dato’ Dr Goh Ai SimHospital Pulau Pinang, Pulau

Pinang, Malaysia

Dr Habsah AzizHospital Canselor Tuanku Muhriz,

Kuala Lumpur, Malaysia

Associate Professor Dr Ikmal Hisyam Bakrin

Universiti Putra Malaysia, Selangor, Malaysia

Dr Ng Soo ChinSubang Jaya Medical Centre,

Selangor, Malaysia

Dr Abu Dzarr AbdullahUniversiti Sains Malaysia,

Kelantan, Malaysia

Dr Henning Loo Cheng Kien

Sunway Medical Centre Velocity, Selangor, Malaysia

Associate Professor Dr Ramliza Ramli


Dato’ Dr Chang Kian Meng

Sunway Medical Center, Selangor, Malaysia

Dr Birinder Kaur Sadu Singh


Dr Jameela SatharAmpang Hospital, Selangor,

Malaysia

Associate Professor Dr Wan Fariza Wan

JamaludinPusat Terapi Sel, HCTM, Kuala

Lumpur, Malaysia

Dato’ Dr Suresh Kumar Chidambaram

Sungai Buloh Hospital, Selangor, Malaysia

Dr Chin Sze PiawCMH Specialist Hospital, Negeri

Sembilan, Malaysia

Faculty


Dr Lam Chee LoongUniversity of Malaya Medical

Centre, Kuala Lumpur, Malaysia

Dr Nor Hafizah AhmadNational Blood Centre, Kuala

Lumpur, Malaysia

Dr Tan Sen MuiAmpang Hospital, Selangor,

Malaysia

Dr Lavitha SivapathamAmpang Hospital, Selangor,

Malaysia

Dr Mohd Haris Fadzillah Abdul Rahman

Subang Jaya Medical Centre, Selangor, Malaysia

Dr Thanuja Mahaletchumy

Hospital Canselor Tuanku Muhriz , Kuala Lumpur, Malaysia

Ms Nik Syazana Izyan Saffery

Cytopeutics Sdn Bhd, Selangor, Malaysia

Dr Lew Kian NianHealth Informatics Center,

Planning Division, Ministry of Health, Kuala Lumpur, Malaysia

Dr Mohammad Firdaus Abdul Aziz

Faculty of Law, University of Malaya, Kuala Lumpur, Malaysia

Dr Veena SelvaratnamAmpang Hospital, Selangor,

Malaysia

Mr Timothy Lim Say WaiPlutonet Sdn Bhd, Selangor,

Malaysia

Dr Lim Soo MinSultanah Aminah Hospital, Johor,

Malaysia

Dr Sharifah Shahnaz Syed Abd Kadir

Ampang Hospital, Selangor, Malaysia

Dr Toh See GuanTuanku Ja’afar Hospital, Negeri

Sembilan, Malaysia

Faculty

Dr Jerome Tan Tsen Chuen

Ampang Hospital, Selangor, Malaysia


Faculty

Professor Dr Mohamad MohtyA full Professor of Hematology and head of the Hematology and Cellular Therapy Department at the Saint-Antoine Hospital and Sorbonne University in Paris, France. He obtained his medical degree from the University of Montpellier, France, and his Ph.D. from the University of Marseille, France. He is also head of a translational research team (Inserm) at the Saint-Antoine Research Centre in Paris.

Dr. Mohty is the past president of the European Society for Blood and Marrow Transplantation (EBMT) and the current chairman of the Acute Leukemia Working Party of the EBMT. He is also the founder and chairman of the International Academy for Clinical Hematology (IACH) and board member of the EBMT and the Intergroup Francophone du Myeloma (IFM).

In addition to publishing more than 780 peer-reviewed articles in the field of stem cell transplantation, leukemia, and myeloma, Dr. Mohty also serves as Editor-in-Chief of the journals Bone Marrow Transplantation and Clinical Hematology International. He also serves as an editor, board member, and/or reviewer across numerous other reputable journals.

Professor Dr Cameron Turtle Professor Dr Cameron Turtle is a licensed physician and serve as an Attending Physician on the HCT service and the Immunotherapy Service at FHCRC, Seattle Cancer Care Alliance (SCCA), and the University of Washington Medical Center. He completed medical and specialist training in Australia and a 6-year training program of the Joint Specialists Advisory Committee, which includes Fellowships of the Royal Australasian College of Physicians and the Royal College of Pathologists of Australasia in hematooncology.

Professor Dr Christopher Ward Professor Ward is a clinical haematologist based at Royal North Shore hospital, with an academic appointment in the Faculty of Medicine, University of Sydney. His clinical interests are in coagulation, particularly venous thromboembolism and platelet disorders, myeloproliferative disorders and myeloma. He runs the thrombosis and anticoagulation clinics at RNS and supervises outpatient management of venous thrombosis. Prof Ward is the lead investigator at RNS for clinical trials of new anticoagulants and therapies for thrombocytopenia.

As Director of Research for the Department of Haematology and Transfusion Medicine, he supervises several research groups investigating platelet function disorders, hypercoagulable states including cancer-related thrombosis, myeloproliferative disorders and the development of stem cell-based therapies. Professor Ward coordinates undergraduate teaching in the Department and supervises a number of postgraduate students in research and clinical trial posts. He is active in regional and international professional societies, with leadership positions in the International Society of Thrombosis and Haemostasis and American Society of Hematology.

Special interests in thrombophilia, platelet disorders and vascular biology, myeloma.


Faculty

Professor Dr Constantine TamProfessor Constantine (Con) Tam is Head of Lymphoma Service at Alfred Health, and Professor of Haematology at Monash University. Con received his M.B.B.S.(Hons) and M.D. degrees from the University of Melbourne. After dual training in Haematology and Haematopathology, Con completed his Leukemia Fellowship at MD Anderson Cancer Centre in Houston, Texas. Prior to moving to the Alfred, Con served as Disease Group Lead for Low Grade Lymphoma and CLL at Peter MacCallum Cancer Centre & Royal Melbourne Hospital for over 10 years. Con is passionate about developing new treatment for blood cancers. He is the global lead for the BTK inhibitor zanubrutinib, and oversaw its development from the first human dosed (in Melbourne) to successful international licensing studies worldwide. Con designed and performed the first global study to combine ibrutinib and venetoclax, publishing the results in the New England Journal of Medicine 5 years after inception. In 2015, he became the Australian lead for the pivotal study of Tisagenlecleucel in diffuse large B-cell lymphoma, leading to public funding for CAR T-cells as standard treatment in Australia. The publication record for Con includes 240 peer-reviewed papers in New England Journal of Medicine, Lancet, Journal of Clinical Oncology, Blood and other top-tier journals. His work has been cited >17,000 times in the literature. Con is the current Lymphoma Editor for Blood Advances.

Professor Dr Erica WoodProfessor Erica Wood is a Transfusion Medicine Specialist, and Head of the Transfusion Research Unit at DEPM. She is an NHMRC Leadership Fellow (Level 2, 2020-2024). Erica also works as a Consultant Haematologist at Monash Health and holds an honorary Consultant Haematologist appointment at Peter MacCallum Cancer Centre/Victorian Comprehensive Cancer Centre. Erica is a member of the World Health Organization’s Expert Advisory Panel on Transfusion Medicine, and the WHO Guideline Development Group on Anaemia. She has served as a WHO regional advisor in blood safety. Erica is immediate past president and member of the Board of the International Society of Blood Transfusion and a member of several of its working parties, including clinical practice, haemovigilance and transfusion-transmitted infections. Erica is the immediate past-President of the International Haemovigilance Network, promoting haemovigilance world-wide and supporting haemovigilance systems in their work.

Erica is also past-President of the Australian and New Zealand Society of Blood Transfusion and in 2016, delivered the Ruth Sanger Oration at the Society’s Annual Scientific Meeting - the Society’s highest honour. She is presently a member of the ANZSBT Research Committee. Between 2012 and 2015 Erica served as Chief Examiner in Haematology for the Royal College of Pathologists of Australasia, and she was Associate Chief Examiner from 2008-2012.

Erica is a founding member of ‘Blood Matters’, a Victorian Department of Health transfusion practice improvement collaborative, and between 2016-2013 she chaired its Serious Transfusion Incident Reporting (STIR) haemovigilance program. In 2013 Erica was awarded a Churchill Fellowship to support her work in patient blood management practice and research.


Professor Dr John Moore John Moore graduated from Sydney University in 1989. He trained in haematology at the Royal North Shore Hospital, The Westmead Children’s Hospital and conducted post graduate training in London. He was the bone marrow transplant co-ordinator at the Royal Free Hospital, London from 1997-98 before returning to Australia to conduct clinical and immunological research into haematopoietic stem cell transplant. He is a fellow of both the College of Physicians and Pathologists. He completed a Doctorate of Medicine at St. Vincents Hospital whilst researching the role of Haematopoietic Stem cell Transplantation for Severe Rheumatoid Arthritis.

He is currently a Senior Staff Specialist in the Haematology Department at St.Vincents Hospital and a Visiting Medical Officer at St. Vincents Private Hospital. He was apointed Professor of Medicine (conjoint – UNSW) in April 2022 and The Chong Family Director of Cellular Therapies at St Vincents Hospital in July 2021.

Dr Moore has extensive experience in stem cell transplantation and immunotherapy spanning over 25 years. He has been an active member of the stem cell transplant community in Australia and internationally. He was the Chair of the Bone Marrow Transplant Committee of the Australian Leukaemia and Lymphoma Group (ALLG) from 2004-2006. He is a member of the Auto-Immune Sub-Committee of the European Group for Blood and Marrow Transplantation (EBMT) and on the Worldwide Network for Blood and Marrow Transplantation (WBMT), Education and Dissemination Committee. He is on the scientific committee of the Asia-Pacific Blood and Marrow Transplantation group (APBMT).

Dr Moore is the clinical lead of the NSW state wide service of stem cell transplantation for auto-immune diseases. This program is the largest in Australia and the second largest contributor to the EBMT database. He is the principal investigator of the Australian Haploidentical stem cell transplant trial currently being conducted from St Vincents Hospital and the Australasian Bone Marrow Transplant Recipeints Registry (ABMTRR). He has published extensively in the field of stem cell transplantation with over 100 publications in the area. He is team leader of the stem cell transplant group in the Blood Diseases and Cancer laboratory at the Lowy Packer building.

Faculty

The Transfusion Research Unit (TRU) at Monash University operates a number of regional and national registries to evaluate clinical practice and patient outcomes for important blood disorders, including massive transfusion, aplastic anaemia and other bone marrow failure syndromes, fetomaternal alloimmune thrombocytopenia (FMAIT), haemoglobinopathies (thalassaemia and sickle cell disease), thrombotic thrombocytopenic purpura (TTP), lymphoma and myeloma. The TRU also performs clinical trials, systematic reviews, health economics analyses and a number of other research and teaching activities across the spectrum of blood diseases. This work is supported by the NHMRC (including through a 5-year Synergy Grant 2020-2024), Medical Research Future Fund, national blood services, Australia’s National Blood Authority, and a wide range of industry, community and philanthropic partners.

In 2020, Erica was awarded the inaugural Fiona Stanley Prize from the NHMRC for the top-ranked Synergy grant application in 2019.

Faculty

Professor Dr Matthew J Matasar Consultant Medical Oncologist/Haematologist & Medical Director of MSK Bergen Memorial Sloan Kettering Cancer Centre. Prof Matasar obtained his medical degree from Harvard Medical School, residency at Columbia University Medical Centre and fellowship in Medical Oncology/hematology at Memorial Sloan Kettering Cancer Center/Weill Cornell Medical College. He was awarded the John J. Kenny Award by Leukemia & Lymphoma Society in 2017. Prof Matasar is a medical oncologist/hematologist who focuses on caring for patients with lymphoma. He is an associate editor of ASH clinical news and is an appointee for National Committee on Quality for American Society of Hematology (ASH). His research interests focus on improving our understanding of the long-term effects of lymphoma treatments, and on studying new ways to improve the quality of life for survivors of lymphoma. He is the section head for aggressive B-cell Lymphoma and is actively exploring new treatments in the management of high-risk aggressive lymphoma and certain uncommon types of non-Hodgkin lymphoma.

Professor Dr Martin GriesshammerMedical Director in the Department of Haematology, Haemostaseology, Oncology and Palliative Care at the Johannes Wesling University Clinic in Minden. Chair of Internal Medicine at the Johannes Wesling University Clinic. Prior to this appointment, he was Vice Head of the Department of Haematology and Oncology at the University of Ulm.

Under Professor Griesshammer’s guidance, the Johannes Wesling University Clinic in Minden serves many haematological patients, providing outpatients and inpatient services, peripheral blood stem cell transplantation, haemostaseology, oncology and palliative care.

Professor Dr Renato BassanRenato Bassan is Director of the Hematology Unit at Venice Hospitals, Italy. Dr Bassan obtained his degree in medicine and completed his postdoctoral fellowship in haematology at Padua University, Italy. He then started his work as full-time haematologist at Bergamo Hospital, Italy, where he set up the leukaemia diagnostic section, the autologous bone marrow transplantation section and the leukaemia clinics. Dr Bassan was trained in onco-haematology at St. Bartholomew’s Hospital in London, UK, lately reaching the position of Honorary Consultant. He assumed his current position in 2011.

Professor Dr Kwong Yok Lam Professor Kwong is Chief of the Division of Haematology, Oncology and Bone Marrow Transplantation at the Department of Medicine, School of Clinical Medicine, The University of Hong Kong. He is a Chui Fook-Chuen Professor in Molecular Medicine. He is specialized in haematology and haematopathology. His clinical work focuses on the management of haematological malignancies. His team has especial interests in the treatment of leukaemias and T-cell and natural killer cell malignancies. His research centres on the molecular pathogenetic pathways and novel treatment modalities in haematological neoplasms. Together with the clinical pharmacology team in his department, Professor Kwong has pioneered the development and use of oral arsenic trioxide in the treatment of acute promyelocytic leukaemia and other blood cancers. His research team is also actively involved in defining the molecular defects and optimal treatment protocols for T-cell and natural killer cell lymphomas, which are neoplasms prevalent in Asian populations.

Dr Bassan’s main professional interest is therapy of acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia. He has led several prospective Phase 2 and 3 trials for the Northern Italy Leukemia Group (NILG), and is involved in new studies and collaborations with the Italian Group for Haematological Diseases in Adults (GIMEMA) and the European Working Group on Adult ALL (EWALL).

Faculty

Professor Dr Roopen AryaProfessor Roopen Arya MA PhD FRCP FRCPathRoopen Arya is Clinical Director for Haematological Medicine at King’s College Hospital in London. He is also Director of King’s Thrombosis Centre and Professor of Thrombosis and Haemostasis at King’s. He trained at Oxford and King’s. His main interests are venous thromboembolism, thrombophilia, and women’s health. He is passionate about thrombosis research and advancing safety and quality of care through innovative and patient-centric approaches to thrombosis care. He is Director of the National VTE Exemplar Centres Network in England.

Professor Dr Sylvie Freeman Sylvie Freeman is Professor of Immunohematology at the University of Birmingham, UK, honorary consultant haematologist at University Hospitals Birmingham and director of the University of Birmingham Clinical Immunophenotyping Service for the diagnosis and monitoring of hematological malignancies.

Training as a hematologist and clinician scientist in Oxford with further clinical rotations at University College Hospital London and Bristol, UK focussed her interests onto predicting treatment resistance in acute myeloid leukemia and myelodysplasia when starting in Birmingham.

Prof Freeman pioneered and implemented flow cytometric MRD methodology for the UK National Cancer Research Institute (NCRI) acute myeloid leukemia trials. This has generated an evidence-base for risk adaptive therapy in acute myeloid leukemia. She co-leads a combined immunophenotypic /molecular MRD monitoring strategy for the NCRI UK trials and provides the UK reference service for flow cytometric MRD in acute myeloid leukemia and myelodysplasia. Prof Freeman’s ongoing efforts to optimise the detection of residual leukemic cells and facilitate standard of care testing are strengthened by an international collaborative network that includes the UK NCRI AML Working Group, the European LeukemiaNet AML MRD Working Group and the American Society of Hematology International Consortium Acute Leukemia Laboratory Committee.

Professor Dr Xiao-Jun Huang • Chairman, Peking University Institute of Hematology • Director, Department of Hematology, Peking University People’s

Hospital • Director, Executive Committee of Asia Pacific Hematology Consortium • Director, National Clinical Research Center for Hematologic Diseases,

P.R.China• Chairman, Chinese Association of Hematologists, CMDA• Chairman, Committee of Experimental Hematology, Chinese

Association of Pathophysiology• Director, China Marrow Donor Program

Faculty

Associate Professor Dr Elizabeth TeggAssociate Professor Elizabeth Tegg is a dual trained pathologist in Haematology and Genetics. She is currently based at The Institute of Clinical Pathology and Medical Research, which is part of New South Wales Health Pathology at Westmead Hospital. She is head of department of both Hematology and Genetics where she oversees a busy tertiary referral laboratory as well as a network of Branch laboratories across NSW. She has undertaken a PhD in the genetic predisposition of Haematological malignancies and continues an active research interest in this field. Her area of interest is in the genetics of haematological malignancies.

Associate Professor Dr Koh Liang Piu A/Prof Koh is a senior consultant at the Department of Haematology-Oncology. After receiving his undergraduate medical degree from the National University of Singapore, he continued his internal medicine training before obtaining his membership from the Royal College of Physicians of the United Kingdom. He then undertook his advanced specialist training in haematology before pursuing his training in haematopoietic stem cell transplantation under the Adult Bone Marrow Transplant (BMT) Program at the Duke University Medical Center in USA. His research interest focuses mainly on clinical haematopoietic stem cell and umbilical cord blood transplantation for adults with haematological diseases.

Associate Professor Dr Nada Hamad A/Prof Nada Hamad is a senior staff specialist bone marrow transplant, cellular therapies, clinical and laboratory haematologist at St Vincent’s hospital in Sydney, where she is also director of the haematology clinical trials unit. She is President of Australia and New Zealand Transplant and Cellular Therapies and chairs a number of national and international committees in the field of transplantation and cellular therapies. She studied Medicine at the University of Sydney and completed her Haematology training in Sydney. Prior to her career in medicine, she completed a Bachelor of Science and Master of Science in Forensics, working in this field for a short period of time. She completed two post-graduate fellowships in BMT and lymphoma at the Princess Margaret Cancer Centre in Toronto Canada through the University of Toronto. She is an active clinical trialist and researcher with a special research interest in graft versus host disease. She is chair of the Australasian Leukaemia and Lymphoma Group transplant and cellular therapies working party and a member of the Scientific Advisory Committee. She is also a member of the National Blood Cancer Taskforce. A/Prof Hamad also has an academic interest in gender equity, diversity and inclusion in medicine (EDI). She is the deputy co-chair of the EDI in Medicine committee at the University of New South Wales in Australia the EDI lead for the Lancet Haematology amongst a number of other EDI committee leadership positions and memberships.

Faculty

Associate Professor Dr Naval DaverDr Naval Daver is an associate professor and director of the Leukemia Research Alliance Program in the Department of Leukemia at MD Anderson Cancer Center (MDACC) in Houston, Texas, USA. He is a clinical investigator with a focus on molecular and immune therapies in acute myeloid leukemia (AML) and myeloid disease, and is principal investigator on more than 25 ongoing institutional, national, and international clinical trials in these diseases, including multiple registration and label enabling trials.

These trials focus on developing a personalized therapy approach by targeting specific mutations or immune pathways expressed by patients with AML, evaluating novel combinations of targeted, immune, and cytotoxic agents, and identifying and overcoming mechanisms of resistance. He is especially interested in developing monoclonal and bispecific antibodies, immune checkpoint, CD47, NK and T-cell based approaches, as well as combinations of targeted and apoptotic therapies in AML, and he is leading a number of these trials at MDACC. Dr Daver has published over 300 peer-reviewed manuscripts and is on the editorial board of numerous hematology journals. He also serves as Chair on numerous national and international meetings and educational platforms.

Associate Professor Dr Peter Mollee Dr Mollee practices as a consultant haematologist in clinical and laboratory haematology at the Princess Alexandra Hospital and is Associate Professor with the University of Queensland Medical School. He is Chairman of the Australasian Leukaemia and Lymphoma Group (ALLG) where he also leads the Myeloma Working Party. He holds appointments with the Medical Scientific Advisory Group of Myeloma Australia, Australian Amyloidosis Network, National Blood Cancer Taskforce and chairs the AACB Monoclonal Gammopathy Working Group. Dr Mollee obtained a Masters in Clinical Epidemiology with a specialisation in Research Protocol Design and has a particular interest in amyloidosis and the plasma cell dyscrasias. He heads the Myeloma Service as well as the Queensland Amyloidosis Centre which runs one of the few clinics in Australia dedicated exclusively to the care of patients with amyloidosis.

Assistant Professor Dr Francesca LimAssistant Professor Francesca Lim is a Consultant Hematologist at Singapore General Hospital and the Assistant Medical Director at the Cell Therapy Facility, Health Science Authority (HSA). Dr Lim is also the Principal Lead of Education and the Lead of Cellular Immunotherapy for adult blood cancers of the SingHealth Duke-NUS Cell Therapy Centre (SDCT).

Dr Lim spent 2 years training at MD Anderson Cancer Center on CAR T cell therapy particularly on CAR NK cell therapy under Professor Katy Rezvani as well as in the Good Manufacturing Processing Facility (GMP). Since her return from MD Anderson Cancer Center, Dr Lim has been instrumental in supporting and coordinating the Cell Therapy Program at SGH Haematology, SingHealth, both at the clinical, research and translational level.

Faculty

Dr Anna Sureda Anna Sureda, (MD, PhD) is nowadays the Head of the Clinical Hematology Department of Institut Català d’Oncologia – Hospitalet, Barcelona. She had previously been a Senior Consultant in Hospital de la Santa Creu i Sant Pau, Barcelona (from January 1991 to December 2010) and a Senior Consultant focused in lymphomas and hematopoietic stem cell transplantation (HSCT) at Addenbrookes–Cambridge University Hospital, UK (December 2010 – December 2012). Anna Sureda has focused her career on clinical investigations into the treatment of Hodgkin’s lymphoma, non-Hodgkin’s lymphoma and multiple myeloma patients evaluating novel therapies such as immunotherapy combined with stem-cell transplantation. Anna Sureda was appointed Chairperson of the Lymphoma Working Party (LWP) of the European Group for Blood and Marrow Transplantation (EBMT) from March 2004 to March 2010 and Secretary of the same organization from March 2010 to March 2016. She was elected co-chair of the Lymphoma Committee of the Center for International Blood and Marrow Transplant Research (CIBMTR) and has served the organization in this position from February 2015 to February 2019. She was subsequently appointed as member of a large non-US Transplant Center in the Advisory Committee of the CIBMTR (from February 2019). Anna Sureda is President of the Spanish Society of Hematopoietic Stem Cell Transplantation and Cellular Therapy (GETH-TC) and, from March 2022, President of the EBMT. Anna Sureda is regular reviewer of several peer reviewed journals (Blood, Annals of Oncology, Bone Marrow Transplantation, The Hematology Journal, The European Journal of Hematology y Annals of Hematology) and has co-authored more than 400 manuscripts.

Dr Chen Yunxin Dr. Chen is a Consultant Haematologist at Singapore General Hospital, and Clinical Deputy Lead (Adult Blood Cancer) and Co-Lead (Education) at the SingHealth Duke-NUS Cell Therapy Centre. She specialises in the care of patients with multiple myeloma and lymphoproliferative disorders.

She completed her Health Manpower Development Programme on immunotherapy at the Memorial Sloan Kettering Cancer Center where she was involved in developing novel cellular therapeutics for treatment of multiple myeloma as well as myeloma CAR T cell clinical trials. She works with a dedicated team of physicians and allied health professionals in the Haematopoietic Stem Cell Transplant Programme at SGH to deliver CAR T cells to patients as well as to develop outpatient transplant services.

Dr Colin Phipps DiongDr Colin Phipps Diong is a Senior Consultant, Haematologist at Parkway Cancer Centre. His subspecialty interest is in lymphoma, leukaemias and myeloma, as well as haematopoietic stem cell transplantation.

Dr Colin Phipps Diong received his medical degree from the National University of Ireland in 2002 and subsequently completed Internal Medicine residency and specialist training in Haematology at Singapore General Hospital. He obtained his MRCP (UK) and FRCPath (UK) in 2006 and 2011, respectively. He was awarded the HMDP fellowship to pursue subspecialty training in Lymphoma and Bone Marrow Transplantation at the renowned Fred Hutchinson Cancer Research Centre in Seattle.

Dr Colin Phipps Diong spent ten years with the Department of Haematology at Singapore General Hospital (SGH). He was appointed Lymphoma Director in 2012 and helped build the lymphoma program, later becoming Lymphoma Lead for the SingHealth-DUKE Blood Cancer Centre, which brought together lymphoma teams from SGH and National Cancer Centre Singapore. He has overseen the management of hundreds of patients with complex blood cancers, including

resistant lymphomas and those undergoing transplantation. He also headed numerous Pharmaceutical-sponsored and Investigator-initiated Clinical Trials. Through Investigator-initiated Trials, he designed treatment schema incorporating novel targeted agents and immunotherapies into current standard treatment in efforts to overcome treatment-resistance.

Dr Colin Phipps Diong has also been actively involved in undergraduate and postgraduate training of young Doctors in Singapore, serving in many educator roles, including postgraduate mentor, Senior Lecturer with the Yong Loo Lin School of Medicine, National University of Singapore (NUS), MBBS examiner, and Assistant Adjunct Professor with the DUKE-NUS Graduate Medical School. He currently sits on the Residency Advisory & Exam Committees for Haematology Training in Singapore, Medical Panel for Bone Marrow Donor Program Singapore, and Chairs Board F of the Ethics Committee in SingHealth. He has authored more than thirty papers in peer-reviewed journals, including Transplantation, Critical Reviews in Oncology-Haematology, and Bone Marrow Transplantation. His expertise in the field of lymphoma and bone marrow transplantation has led him to serve as Advisor to numerous regional and international Expert Panels and Education Programs.

Faculty

Dr Daryl Tan Chen Lung Dr Daryl Tan is a haematologist at Mount Elizabeth Novena Hospital, Singapore. He trained in internal medicine and haematology at the Singapore General Hospital, and pursued postdoctoral training and clinical research in the field of lymphoma at Stanford University, USA. He was formerly the clinical lead for the lymphoma and myeloma services at the Singapore General Hospital, and spearheaded several clinical trials examining novel approaches in treating lymphoma and multiple myeloma.

In 2011, Dr Tan helped set up a comprehensive haematology service and was the director of research at a private hospital in Singapore. He integrated research with clinical practice, availing novel therapeutics for cancer patients failing standards of care. He was an assistant professor at the Duke-NUS Graduate Medical School, and received several research grants from the National Medical Research Council, Singapore Health Foundation, and the Singapore Cancer Syndicate.

He was elected into the International Myeloma Working Group in 2014 and also sits on the advisory panel of the International Myeloma Foundation’s Asia Myeloma Network. He has delivered more than 80 invited lectures on the treatment of lymphoma and multiple myeloma at international and regional conferences. Dr Tan is a board member of the Chapter of Haematologists and is appointed by the Ministry of Health as an advisor for the Residency Advisory Committee for Haematology training in Singapore. His continued affiliation with the academic hospitals allows him to contribute to post-graduate teaching, and to advise patients on participation in clinical trials for lymphoma and multiple myeloma. He was the principal investigator of more than 40 investigator-initiated and industry-sponsored clinical studies. His research has led to several international presentations and more than 100 publications in high-impact factor scientific journals including first-authored articles in the Lancet Oncology, Blood and the Annals of Oncology.

His expertise in lymphoma and multiple myeloma was recognised by the publication of two lead-author review articles on their respective treatment guidelines in Lancet Oncology in 2014. Dr Tan’s work on immunotherapy in NK/T-cell lymphoma has led to its endorsement on the American NCCN cancer treatment guidelines in 2018. Dr Tan has received several awards including the Singapore Health Service Quality Service Gold Award in 2011 and the Courage Medal during the Singapore SARS epidemic in 2004.

Faculty

Dr Kenichiro Hasumi Dr. Kenichiro Hasumi of Tokyo, Japan is a physician, specialized in cancer immunotherapy and terminal care. He is also a researcher and visionary, focused on the development of cancer vaccines and improved clinical treatments to achieve better patient outcomes with a higher quality of life. He is devoted to his patients and their families, and to improved cancer education, understanding, and awareness on a global scale.

In 1931, his late father Dr. Kiichiro Hasumi advanced the hypothesis of cancer propagation by virus and started studies to prove his theory. And after seventeen years of meticulous research and development efforts, the clinical application of the Hasumi Vaccine as the first and most used cancer vaccine in the history of medicine was started and has been clinically prescribed to more than 500,000 patients cumulatively till today for more than seventy years.

In 1988 after completing his clinical training at the Institute of Medical Science, the University of Tokyo (IMSUT), Dr. Hasumi succeeded his father in this pioneering work to continue research and development, and the treatment of cancer patients. In 1999, Dr. Hasumi established the Hasumi International Research Foundation (HIRF) as a nonprofit organization in the United States HIRF has been sponsoring the International Cancer Vaccine Symposium since 2001. The primary purpose of HIRF is to conduct and support scientific research in connection with finding a cure for various forms of cancer, particularly with the use of immunotherapy.

Dr. Hasumi has developed and patented a dendritic-cell-base cellar immunotherapy for advanced and recurrent cancer called HITV (Human Initiated Therapeutic Vaccine) therapy, aiming the complete remission of cancers. Currently, with his ever-growing vision to help cancer patients, Dr. Hasumi has been supporting various cancer researches in the United States, Japan, Taiwan, Malaysia, China and Germany.

Dr Ng Chin Hin Dr Ng Chin Hin is a haematologist practising in Gleneagles Hospital, Singapore. He specialises in blood cancers such as leukaemia and he has a special interest in leukaemia stem cell and biomarker research, and targeted therapy in acute myeloid leukaemia. He is experienced in the treatment and management of a wide range of conditions like anaemia, bleeding disorders such as haemophilia, and other blood disorders like myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPN), thrombocytosis. Dr Ng was the leukaemia lead at National University Cancer Institute of Singapore (NCIS) and has more than 10 years experience in this field. He also served several years as the research director for the haematology division and chairperson for the leukemia tumour board in NCIS. Prior to joining Gleneagles Hospital, he was an assistant professor in the Department of Medicine in NUS and was actively involved in training the undergraduates there. Dr Ng has

Dr Drew ProvanI trained in molecular biology before studying medicine. After various junior medical posts I undertook research at Harvard Medical School. I have been a consultant in London since 2000. My primary clinical and research interest is immune thrombocytopenia. However as well as Clinical medicine I currently run a business which offers presentation coaching, slide design and illustration. I very much enjoy public speaking and helping others overcome their fears, designing better slides and generally improving their delivery. This is my primary focus at present .

Faculty

Dr Rajat BhattacharyyaRajat did his undergraduate medical training and post graduate paediatric training (MD paediatrics) from Medical College Kolkata. Then he pursued his further paediatric and haematology training in UK 1998- 2010 working in different centres initially in general paediatrics and then haematology oncology. He completed Specialist Registrar training (CCT in Haematology UK). He also did 1 year post CCT fellowship in paediatric haematology oncology in Vancouver Children’s Hospital, Canada. Currently he is working as a senior consultant in KK Hospital since March 2013. His special interest is benign haematological conditions including ITP, bone marrow failure syndromes and also malignant haematological conditions including leukaemia and stem cell transplantation. He has initiated the Haploidentical stem cell transplantation programme in KK Hospital in Singapore with rapid evolution of the selective T cell depletion technique in the clinical practice.

Dr Robin Gasiorowski Dr Robin Gasiorowski completed medical training at Cambridge University and University College London, before moving to Australia in 2004. Following specialist haematology training at Royal Prince Alfred and Concord hospitals he now works as a clinical and laboratory haematologist, with appointments at Concord and Macquarie University Hospitals. He has a particular interest in acute leukaemia and high-grade lymphoma and in 2017 completed his PhD with the Dendritic Cell Research group at the University of Sydney, developing novel therapeutic antibodies for the treatment of Acute Myeloid Leukaemia (AML). Whilst he continues to be contribute to this group’s work, he also has a strong interest in clinical research, particularly in the development of novel immune therapies for patients with haematological malignancies. He has been a principal investigator on a number of industry and ALLG sponsored clinical trials for patients with high grade lymphoma and leukaemia.

Ms Julija Sipavicius Julija is a registered nurse with over 20 years experience in the field of haematology and blood and marrow transplant (BMT) nursing. Having trained in Australia Julija spent 8 years working at the Hammersmith Hospital in London UK where she further established her interest in BMT and undertook a range of post graduate advanced haematology nursing courses. On returning to Australia Julija took a short break from the clinical area, working with the BMT Network of NSW coordinating an acuity research project then as Haematology/BMT content author for the Cancer Institute of NSW. Julija returned to the clinical area as a senior nurse, completing a Masters Degree in Nursing Leadership and then moving to the Royal Melbourne Hospital Clinical Haematology and BMT services as the BMT coordinator, and more recently as a BMT Nurse Practitioner. During this time she successfully completed a second Masters degree in Nurse Practitioner. She is a founding member of the Haematology Society of Australia and New Zealand (HSANZ) Nurses Group, past secretary and co-editor for the HSANZ NG newsletter, and she is an affiliate lecturer at the University of Sydney. Julija currently works as the Haematology/BMT Nurse Practitioner at the Royal North Shore Hospital in Sydney. Again her core clinical work is in BMT with a focus on post-transplant care and long term follow-up, in addition to managing patients with Multiple Myeloma.

published many papers in the Journal of Clinical Pathology and other journals. He was active in clinical research and was the research director for the haematology division in the Department of Haematology-Oncology at NCIS.

Faculty

Emeritus Professor Dr Cheong Soon Keng Professor Cheong is Senior Professor and Dean of the Faculty of Medicine & Health Sciences, Universiti Tunku Abdul Rahman (UTAR), since November 2009. He is currently the Visiting Consultant Haematologist at the Sungai Long Specialist Hospital, Kajang and Brighton Medical Centre, Cyberjaya.He received his basic medical degree (MBBS) from the University of Malaya in 1975, and obtained his postgraduate qualifications in internal medicine MRCP (UK), clinical pathology DCP with distinction (University of London), haematology FRCPA (Australasia) in 1978, 1979 and 1992 respectively. He was elected to fellowship FRCP (Edinburgh and Glasgow) in 1990, FAM (Malaysia) in 1997, and FAM (Singapore) in 2011. For his research contribution, he was elected Fellow of the Academy of Sciences of Malaysia in 2001 and Founding Fellow of the Faculty of Sciences, RCPA (Australasia) in 2011. He was conferred the honorific title, Professor Emeritus, by the National University of Malaysia in 2007.

In 2011, he was appointed Honorary Professor of Universiti Malaya and Senior Fellow of the Academy of Sciences of Malaysia which carries the title “Academician”.

Being an active researcher in basic sciences and clinical haematology, he has authored or co-authored over 500 publications and presentations. He has won numerous research grants and presentation awards. His current research interest is in blood disorders, immunotherapy for cancers, and the application of mesenchymal stem cell and induced pluripotent stem cells in reparative medicine. He supervised or co-supervised 50 Master and 21 PhD theses by research to date.

Presently he also serves as the President of the College of the Pathologists, Academy of Medicine of Malaysia and the Vice-President of the National Cancer Council (MAKNA). He is also an Emeritus Member of the American Society of Hematology.

Professor Dr S Fadilah Abdul WahidProfessor Dr S Fadilah is Senior Consultant Haematologist and Transplant Physician at Universiti Kebangsaan Malaysia Medical Centre (UKMMC) as well as Head of Pusat Terapi Sel, Hospital Canselor Tuanku Muhriz (HCTM). She is currently a Professor of Medicine (Internal Medicine & Haematology) at the Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM). She received her basic medical degree and Masters in Internal Medicine from the UKM Kuala Lumpur.

In 2005, she completed her PhD Degree in Cancer Immunotherapy from the University of Queensland Mater Medical Research Institute in Australia. She had undergone numerous training programs in blood and marrow transplantation in the UK, Japan and Australia. She is a fellow of the Royal College of Physicians (RCPE) Edinburgh. She has been actively involved in basic translational research in hematological malignancies, with a particular niche focus on dendritic cell and stem cell therapy and has been appointed as the principle investigator of numerous investigator initiated (industry-sponsored) clinical trials. She is currently the principal investigator for clinical trials involving dendritic cell-based treatment and CAR-T cell treatment for lymphoma and leukemia for patients in Malaysia.

Being an active researcher in basic sciences and clinical haematology, she has authored or co-authored over 100 publications in peer-reviewed scientific journals for hematological and non-hematological disorders, more than 100 scientific presentations, consensus and clinical practice guidelines and monographs. As a result of collaboration with external medical institutions and industry partners, she has raised large research funds amounting up to RM 20 million and set up several

research groups. She is an editorial board member of several local and international journals and an author for Cochrane systematic review, UK. She supervised and co-supervised 28 Master, 5 Clinical Hematology Subspecialty.

Program and 2 PhD theses to date. She has served as a member of Asia-Pacific boards for multiple myeloma, lymphoma and others . She is also a trainee and examiner in the clinical hematology subspecialty training program and evaluator of the clinical hematologist recognition process in the country. Her expertise experience in the field of cell therapy and blood cancer in the country was recognized when she was appointed as a member of the National Transplant Council, Pharmaceutical Control Bureau, National Science & Research Council and National Stem Cell Committee, MOSTI research proposal panel, MAKNA consultant, Inno Bio Diagnostics, as well as as a manager and advisor to several private biotech companies. Most recently, in 2019, she was appointed as a project leader for the establishment of the International Cancer Vaccine Kuala Lumpur Clinic with full sponsorship from ICVS Tokyo, HIRF.”

Faculty

Professor Dr Bee Ping Chong Dr Bee is a Consultant Haematologist and a lecturer and Professor at the Faculty of Medicine, University of Malaya (UM) and the University of Malaya Medical Centre. He is a member of the Malaysian Medical Association, the Malaysian Society of Haematology and the European Society of Haematology. He has authored or co-authored many peer-reviewed journal articles and meeting abstracts in the field of Haematology. Professor Bee specialized in Haemato-Oncology (Myeloproliferative Disorders, Multiple Myeloma, Lymphomas, Leukaemias, Myelodysplastic syndrome), non-Malignant Haematological disorders (bleeding disorders, Thrombosis and Anticoagulation, Anaemias, Idiopathic thrombocytopenic purpura), Haemoglobinopathy (Thalassaemia, Sickle cell anaemia), paroxysmal nocturnal haemoglobinuria, thrombotic thrombocytopenic purpura and haematopoietic stem cell/bone marrow transplant.

Professor Dr Noraidah Masir Prof. Dr. Noraidah graduated from the Royal College of Dublin, Ireland in 1986 with MBBCh. BAO, LRCP & SI. She then pursued her studies in Master of Pathology (MPath) in Universiti Kebangsaan Malaysia (UKM) in 1994. In 2007, she obtained D.Phil. (Oxon) from the University of Oxford.

Currently, Prof. Dr. Noraidah is a Visiting Consultant Pathologist (Histo and cytopathology) at Pantai Premier Pathology. Prof. Dr. Noraidah also leads the Department of Pathology, Faculty of Medicine (UKM) since 2013. Previously in 1986, she served Hospital Kuala Lumpur as a House Officer and Hospital Tuanku Jaafar, Seremban as a Medical Officer in 1987. Her interest in academic started in 1990 as a Trainee Lecturer in Faculty of Medicine, UKM. After obtaining her Master in Pathology in 1994, she served few government hospitals as an Anatomical Pathologist. Her wide interest has brought her to have a clinical attachment in Haematopathology, John Radcliffe Hospital in the University of Oxford, United Kingdom. In 2007, she completed her PhD thesis in Immunogenotypic studies of human lymphomas.

Faculty

Professor Dr Raja Zahratul Azma Raja Sabudin Dr Raja Zahratul Azma is a Professor of Haematologist with subspecialisation in Molecular Genetic of Haematology Disorders. She has led multiple research projects in the field of haematology covering a wide variety of topics. Her main scientific interests are in blood cell disorders and molecular genetics of haematology diseases with her current researches is centred on thalassaemia, G6PD deficiency, leukaemia and digital haematology. She is presently committee member of Haematology Chapter of College of Pathologist and Human Variome Project Malaysian & South-East Asian Node; and Executive Committee Member of Global Globin Network.

Associate Professor Dr Ikmal Hisyam Bakrin Ikmal Hisyam Bakrin, M.D. is Consultant Dermatopathologist and Medical Lecturer in the Faculty of Medicine and Health Sciences, Universiti Putra Malaysia. He is practicing in HPUPM and Hospital Serdang as well as a visiting pathologist in Pantai Premier Pathology and Hospital Canselor Tuanku Muhriz UKM (HCTM).

He is one of the expert persons for skin pathology in Malaysia and actively involved in dermatopathology clinicopathological conferences (CPCs), seminars, workshops, as well as conferences at national and international levels (Asian Society of Dermatopathology).

Associate Professor Dr Ramliza Ramli Assoc. Prof. Dr. Ramliza Ramli started her career as a lecturer and clinical microbiologist consultant with special interest inantimicrobial stewardship, antibiotic resistance and diagnostic bacteriology over 15 years of experience. She had short-course trainings in antimicrobial stewardship at Taiwan (2006) and Singapore (2017). She has combined her expertise with being appointed as a member of National Antibiotic Resistance Committee, Antibiotic and Infection Control Committee and Antimicrobial Stewardship Committee HCTM UKM. She currently serves as the Head of Bacteriology Unit at the Department of Diagnostic Laboratory Services. She is the internal auditor for Malaysia Society of Infectious Diseases & Chemotherapy (MSIDC), former member of Malaysian Medical Association Foundation Infectious Disease Fund and life-member of the Malaysia Medical Association.

Her extensive experiences include:• Co-Chairperson (Education Committee), College of Pathologists AM

(Malaysia),• Invited Lecturer for various local & international scientific symposiums

and conferences,• External Examiners for research studies in several universities and

organiser of Professional courses & meetings,• Vetting Panel for research proposals for MAKNA Cancer Research

Awards and Research Grants by Ministry of Higher Education (MOHE) Malaysia,

• Life member of College of Pathologists Academy of Medicine, • Life Member of Royal College of Surgeon in Ireland Alumni,

• Life member of University of Oxford Alumni, • Member of European Association of Haematopathology.

Till now, Prof. Dr. Noraidah has published more than 40 research publications, presenting of more than 27 studies and review of more than 9 scientific manuscripts.

Faculty

Associate Professor Dr Wan Fariza Wan Jamaludin Prof Madya Dr Wan Fariza Wan Jamaludin is a consultant physician and clinical haematologist with a deep interest in lymphoproliferative disorders and stem cell transplantations. She was medically trained in the UK and is extensively involved in hematological research with publications in Q1 journals.

Associate Professor Ir Ts Dr Mohd Ridzuan Ahmad I obtained my Dr. Eng. (Micro-nano Systems Engineering) from Nagoya University, Japan in March 2010. I was a research officer in the Department of Robotics and Mechatronics, UTM, from June to November 2002. In 2003, I joined the Faculty of Electrical Engineering as a lecturer. I was promoted as a senior lecturer in 2011. Since 2011, I am a Principal Researcher at the Institute of Ibnu Sina, UTM and from 2014 as an Associate Researcher at the Advanced Photonics Science Institute in UTM. I was promoted to an Associate Professor in June 2017. In teaching, I have taught at the Faculty of Electrical Engineering, Universiti Teknologi Malaysia for fifteen years. I teach core and elective subjects that are related to the electrical engineering at the undergraduate and postgraduate levels. My research interests include multi-agent robotics system, micro/nanomanipulation, nanobiology, nanodevices, and single-cell analysis. I am a member of several professional engineering bodies such as the Institute of Electrical and Electronics Engineers (IEEE), Institute of Engineering and Technology (IET), a life member of Golden Key International Honor Society, a professional engineer of Board of Engineers Malaysia (BEM), a charted engineer of UK engineering council (IET) and a corporate member of Institute of Engineers Malaysia (IEM).

Dr Ng Soo Chin Dr Ng Soo Chin is currently the Consultant Haematologist and Director of Clinical Diagnostic laboratory at Subang Jaya Medical Centre. He was the past President of MSH and Asean Federation of Haematology. He is an avid researcher and has presented and published 245 scientific papers.

Dato’ Dr Chang Kian Meng Dato’ Dr Chang is a consultant hematologist and transplant medicine at Sunway Medical Center. He was the Head of the Department and National Advisor for Haematology at the Ministry of Health for 13 years from 2004-2017. He is board certified by Fellow of Royal College of Physicians (UK), Fellow of Royal College of Pathologists Australasia and the National Specialist Register in Clinical Haematology and Haematology (Pathology). His clinical focus is on red cell and platelet disorders, leukaemias, MDS, lymphomas, multiple myeloma, clotting and bleeding problems, and consultative haematology. He is active in association activities; one of which is that he is a Member of the Asian Lymphoma Study Group and is the Past Chairman of the Medical Research Ethics Committee among others. His procedure focuses on blood and marrow stem cell transplantation, autologous transplants, and allogeneic transplants including sibling donors, unrelated donor, haplo donor and cord blood transplants.

Faculty

Dato’ Dr Suresh Kumar Chidambaram Dr Suresh Kumar is currently the Head of the Department of Medicine and an Infectious Diseases consultant at Hospital Sungai Buloh, Malaysia.

Dr Suresh graduated with an MBBS from the University of Kerala, India in 1993. He then obtained his MRCP (UK) in 1999 from the Royal College of Physicians in UK and Postgraduate diploma in epidemiology in 2009 from London school of Hygiene and Tropical Medicine. He obtained his infectious diseases training in Hospital Kuala Lumpur and Alfred Hospital, Melbourne, Australia. He has been Infectious Diseases Consultant in Hospital Sungai Buloh since 2003. He is also a visiting consultant for National Heart Institute (IJN).

He serves on expert panels for national treatment and practice guidelines relating to infectious diseases including COVID-19, HIV, Dengue, Adult Immunisation, and National antibiotic guidelines. Dr Suresh is actively involved in the Infectious diseases fellowship programme in the country. He is the Past President of the Malaysian Society for HIV Medicine, MASHM.

Dato’ Dr Goh Ai Sim Dato’ Dr Goh Ai Sim (Senior Consultant Haematologist & Head of Dept of Medicine, Hospital Pulau Pinang). Dato’ Dr Goh Ai Sim graduated from University of Malaya in 1991 and did her haematology training in Hospital Kuala Lumpur and Royal Perth Hospital, Australia. She is currently the National Head of Haematology Service in Ministry of Health, Malaysia as well as Penang state advisor for haematology service. She is a Council member in the Malaysian Society of Haematology, chairperson for the MSH training committee and the NSR subcommittee for clinical haematology. She is actively involved in multiple clinical trials related to thalassaemia, hemophilia, leukaemia and PNH.

Dr Abu Dzarr Abdullah Graduated from UKM medical school in 1994. Worked as Medical MO in several hospitals Taiping, Pulau Pinang, Alor Setar and Kubang Kerian before completing MMed in 2002. Joined USM as medical lecturer since 2003. Has been practicing clinical haematology in HUSM since then, as well as teaching and research in internal medicine and haematology. Main interest has been developing medical applications for service as well as teaching and learning.

Dr Birinder Kaur Sadu Singh Dr. Birinder Kaur currently heads the Cytotoxic Drug Reconstitution (CDR) and Parenteral Nutrition Services in UKMMC. Aside from clinical routines, she is also an Associate lecturer with the Faculty of Pharmacy in Universiti Kebangsaan Malaysia. As an experienced senior pharmacist, she is actively involved in training pharmacists and pharmacy assistants from all over the country including Ministry of Health and Private hospitals.on setting up CDR units and safe handling of cytotoxic drugs. She has presented her work locally and in international meetings. In addition, she is an active member of Parenteral & Enteral Nutrition Society of Malaysia, TheInternational Society of Oncology Pharmacy Practitioner (ISOPP) and The International Society of Renal Nutrition and Metabolism (ISRNM). Her areas of research interest includes Safe Handling of Cytotoxic Drugs, Immunonutirition in Critically Ill Patients and Malnutrition in Patients Undergoing Haemodialysis.

Faculty

Dr Chin Sze Piaw Dr Chin Sze Piaw qualified with an MBBS from Newcastle UK in 1995 and obtained his MRCP in 1998. He is currently a consultant physician and cardiologist at the CMH Specialist Hospital and Honorary Fellow of the Centre for Stem Cell Research, Faculty of Medicine & Health Sciences, Universiti Tunku Abdul Rahman.

Dr Chin has served on expert committees for clinical practice guidelines, and several research and registry steering committees for cardiovascular disease and stem cell research. His own research interest in heart failure and stem cell therapy has led to over 60 publications in international peer-reviewed journals and presentations at international medical conferences. Among the cutting-edge research includes the demonstration of clinical anti-inflammatory and immunomodulatory actions of mesenchymal stem cells (MSC) and successful treatments of cardiomyopathy, stroke and diabetes complications and osteoarthritis.

Dr Chin was jointly awarded patents from the USA for his pioneering use of MSC treatment for acute stroke, vernal keratoconjunctivitis and diabetes. His other patents include use of stem cells for severe heart failure, auto-immune disease, pre-diabetes and diabetes complications, and macular oedema. Dr Chin has been a joint recipient of numerous grants for his stem cell research including the ERGS and FRGS grants from the Ministry of Higher Education, the MOSTI Technofund, The Impak Perdana award and the Toray Foundation award from Japan.

In 2018, Dr Chin and colleagues obtained another landmark approval from the regulatory authorities under the Ministry of Health, to undertake a large multicenter clinical trial of acute Graft versus Host Disease (aGVHD). In 2021, Dr Chin was one of several experts from Asia to discuss about use of MSC for COVID-19. Dr Chin Sze Piaw leads the regulatory, pre-clinical and clinical research activities at Cytopeutics.

Dr Habsah Aziz Dr Habsah Aziz obtained her first degree in Biomedical Sciences from University Putra Malaysia in 2002. She then pursued her studies in Master of Biotechnology from Universiti Malaya and PhD in Molecular Medicine from Universiti Kebangsaan Malaysia with a thesis entitled molecular mechanism of relapse in childhood AML. She started her career as scientific officer in the Department of Diagnostic Laboratory Services, Hospital Canselor Tuanku Muhriz in 2002. Currently, Dr Habsah Aziz is a Senior Chief Scientific Officer in the Stem Cell Transplant Unit. Aside from clinical routines, she is also a Technical Assessor for laboratory accreditation scheme of Malaysia Medical Testing MS ISO 15189 for Standard Malaysia since 2013. Dr Habsah Aziz is also actively involved in quality activity namely quality control circle (KIK) and Malaysian Society For Quality In Health (MSQH).

Dr Henning Loo Cheng KienDr Henning Loo Cheng Kien is a Clinical Haematologist at Sunway Medical Centre Velocity, Subang Jaya in Malaysia. He is a member of the Malaysia Society of Haematology (MSH). He did his postgraduate training at University of Malaya and received the Certificate of Specialist Training in Haematology from MSH. His clinical focus are on, Leukemia, Lymphoma, Multiple Myeloma, Myelodysplastic syndrome, Myeloproliferative neoplasm, Haematopoietic stem cell transplant, Bleeding disorders, Anaemia, Venous-thromboembolism and Thalassaemia. In 2019, he have received the Gold award for best clinical abstract at 16th MSH Annual Scientific Meeting. His procedure focuses on Chemotherapy,, Immunotherapy, Targeted therapy, Bone marrow aspirate and trephine, Blood transfusion, Intravenous iron and Haematopoietic stem cell transplant.

Faculty

Dr Jameela Sathar Dr Jameela Sathar is a Consultant Haematologist and former Head of Department of Haematology at Ampang Hospital, Malaysia. Her field of interests are thalassaemia, haemophilia, thrombosis, bleeding disorders and patient blood management (PBM). She is the current President of the Malaysian Society of Patient Blood Management.

Dr Sathar is a well-known speaker at both national and international medical conferences and hosts regular educational workshops for fellow medical doctors on the topic of PBM.

Dr Sathar hopes that inappropriate transfusions of blood and blood components will be reduced with the practice of PBM.

Dr Jerome Tan Tsen Chuen Dr Jerome Tan is the consultant clinical haematologist currently based in Hospital Ampang Selangor, which is the national referral haematology centre for the Ministry of Health, Malaysia. He is also the Head of the CRC Unit in Hospital Ampang and a clinical trainer for the MOH haematology subspecialty programme. He graduated from University of Malaya and obtained his postgraduate MRCP(UK) qualification from the Royal College of Physicians and Masters of Internal Medicine from the National University of Singapore. He is a former council member of Malaysian Society of Haematology and an honorary member of the Asia Pacific Leukaemia Consortium.

His area of interest is mainly in malignant haematology namely in leukaemias, lymphomas & myeloma.

Dr Lam Chee Loong Dr Lam is a Senior Lecturer and Consultant in Palliative Medicine at the University of Malaya. He received a CCT in Palliative Medicine from the Northern Deanery in the UK and worked at the Northern Centre for Cancer Care and the Marie Curie Hospice in Newcastle prior to returning to Malaysia. His main interests are in education, end of life care ethics and strategic development of palliative care nationally.

He has published many studies on end of life care among patients and caregivers, as well as among the doctors in University of Malaya Medical Centre. He also received the Excellence Service award from University of Malaya in 2016. In the past few years, he was the Chairperson of Malaysian Hospice Council, from 2018 to 2020. He was also the Committee Member (Medical Advisor) to Assisi Palliative Care, from 2018 to 2019.

Dr Lavitha Sivapatham Dr Lavitha Sivapatham is a Consultant Obstetrician & Gynaecologist, Paediatric & Adolescent Gynaecologist and Reproductive Medicine Specialist, who underwent training at the Royal Children’s Hospital, Melbourne who is currently attached to Hospital Ampang.

Faculty

Dr Lim Soo MinDr Lim Soo Min is currently a consultant haematologist at Hospital Sultanah Aminah. He had received his training in clinical haematology at Hospital Ampang in 2007 and also a one year clinical attachment at Peter MacCallum Cancer Centre, Melbourne in 2010.

Dr Mohd Haris Fadzillah Abdul Rahman Dr Mohd Haris Fadzillah Bin Abdul Rahman is a Consultant Physician and Haematologist at Subang Jaya Medical Centre, Malaysia. He has done his post-graduate clinical training at the Royal College of Physicians of Edinburg (MRCP) and received his board of certification in Internal Medicine from the Royal College of Physicians, the United Kingdom in 2003. Dr Mohd Haris’s procedures focus on Bone marrow aspiration and trephine biopsy as well as Cancer treatment, Stem cell transplantation. He is a council member of the Malaysian Society of Haematology (MSH) and a member of the Malaysian Society of Transplantation (MST).

Dr Mohammad Firdaus Abdul Aziz Mohammad Firdaus Abdul Aziz is a senior lecturer and a program coordinator of Bachelor of Jurisprudence at the Faculty of Law, Universiti Malaya (UM). His current research interests are in the area of medical law, biosafety law, legal and ethical issues of emerging technologies such as stem cell technology, gene editing, and biobanking. He obtained his BSc (Hons) in Genetics and Molecular Biology from UM. He was awarded the National Science Fellowship to further his studies in MA in Biotechnological Law and Ethics at the University of Sheffield. He later went on to read DPhil in Public Health at St Edmund Hall, University of Oxford. In Oxford, he was based at the Centre for Health, Law and Emerging Technologies to pursue his interest in stem cell law and ethics. He has been involved in developing Bioethics in the Southeast Asia region as a UNESCO Bioethics Trainer. He is also a co-investigator of the UK Wellcome Trust to establish a regional bioethics network between Malaysia, Singapore, and Thailand and a co-investigator of the NIH Fogarty grant to develop a Master of Health Research Ethics at UM, the first of its kind in the region.

Dr Lew Kian Nian As a Principal Assistant Director at the Health Informatics Centre, Ministry of Health Malaysia, Dr Lew is involved in the development, operation and maintenance of patient registry systems, together with a team consisting of IT officers and statisticians.

Faculty

Dr Sharifah Shahnaz Syed Abd Kadir Dr. Sharifah Shahnaz Binti Syed Abd Kadir graduated with MD from University Kebangsaan Malaysia in 2005 and subsequently obtained her postgraduate studies in Internal Medicine from the Royal College of Physicians (MRCP, UK) in 2009. She completed her fellowship in Clinical Haematology in 2017. During her fellowship, she received training in the field of stem cell transplantation from Eppendorf Medical Center, Hamburg, Germany. She currently serves as Haematologist managing general haematology and stem cell transplant cases in Ampang Hospital since 2014. She is actively involved in clinical research and very much interested in malignant haematology.

Dr Tan Sen Mui Dr Tan Sen Mui obtained her basic medical degree locally and MRCP in UK. Started haematology training in the MOH in 2001 and subsequently further has her training in stem cell transplantation followed by research in cancer immunotherapy in University Wuerzburg, Germany.

She has special interest in cancer immunotherapy and actively participated in clinical trials. Currently, she is the senior consultant haematologist & HOD of the Haematology Department in Hospital Ampang, which is the main haematology referral centre in Malaysia.

She is also the past secretary of Malaysian Society of Haematology (MSH) and member of the European Society for Blood and Marrow Transplantation (EBMT).

Dr Thanuja Mahaletchumy Dr Thanuja Mahaletchumy is a consultant nuclear medicine physician and currently the head at Department of Molecular Imaging and Nuclear Medicine, Universiti Kebangsaan Malaysia Medical Center. Her main expertise is in hybrid PET/CT and SPECT/CT imaging, with a focus on oncologic imaging. She also has special interest in radionuclide therapy.

Dr Nor Hafizah Ahmad Dr. Nor Hafizah Ahmad is a Transfusion Medicine Specialist who is currently the Head of Clinical Transfusion Division in National Blood Centre, Kuala Lumpur, Malaysia heading both Immunohematology and Clinical Transfusion Laboratory. She has completed her subspecialty training in Patient Blood Management/Clinical Transfusion and Immunohematology in Sweden recently and has been regularly involved in conducting training around the country for many years in both areas. She has been appointed as the chairperson for National Rare Donor Program since 2014 and is actively involved in the implementation of Patient Blood Management and Massive Transfusion Protocol in her place. Apart from that she had also been invited as speaker in various conferences at national and international level.

Faculty

Dr Veena Selvaratnam Dr Veena Selvaratnam is a Haematologist based in Hospital Ampang. She completed her MRCP Uk in 2009 and her FRCPath (Hematology) in 2019. She underwent her Haematology sub-speciality training in 2013 -2017 during which she spent a one-year stint at the Hammersmith Hospital London to gain more experience in managing patients with bleeding and clotting disorders. She is currently in charge of the Haemophilia and bleeding disorder clinic and the Clinical Haematology Reference Laboratory in Hospital Ampang. She is also actively involved in clinical trials and education programs. Her areas of interest are bleeding disorders including acquired bleeding disorders, obstetric haematology as well as thrombophilia.

Dr Toh See Guan Dr Toh did his clinical hematology training at Hospital Pulau Pinang and Hospital Ampang from 2011 till 2014. He is now working as clinical hematologist at Hospital Tuanku Ja’afar Seremban.

Ms Nik Syazana Izyan Saffery Graduated from pioneer batch of Masters in Regenerative Medicine from National Orthopaedic Centre of Excellence in Research and Learning (NOCERAL), University of Malaya.

Currently working as Projects Coordinator at Cytopeutics Sdn Bhd, managing and overseeing stem-cell based clinical trials in collaboration with MOH hospitals and funded by MOSTI.

Mr Timothy Lim Say Wai Mr Timothy has been involved in manufacturing of cell therapy product for the past 10 years and has experience in various types of cell culture such as Cytotoxic T-cells, NK cells and CAR-T cells. He is currently involved in CAR-T cells manufacturing at Plutonet Sdn Bhd.

Programme Detail - Day 19th August 2022 - Tuesday

continue next page

Time (GMT+8) Virtual Hall A Virtual Hall B On Demand


Programme Detail - Day 19th August 2022 - Tuesday

Programme Detail - Day 210th August 2022 - Wednesday


0800 - 0930Session 1.A:

Updates On Haematopoietic Cell Transplant (HCT)

Session 1.B:Lymphoma Treatment Dilemmas/

Challenges (Case-based)

Symposiums

Free Paper Oral and E-Poster

Presentations

Sponsored Symposiums

ChairpersonProf Dr S Fadilah Abdul WahidPusat Terapi Sel-UKM, Kuala Lumpur, Malaysia

Updates On Hematopoietic Stem Cell Transplantation: Indications and Transplant ProtocolProf Dr Xiao-Jun Huang Peking University People’s Hospital & Institute of Hematology, Beijing, China

Haploidentical vs. MUD HSCT - Which One to Choose?Prof Dr John Moore St. Vincent’s Health Network, Sydney,Australia

Haematopoietic Stem Cell Transplant for Non Malignant Haematological ConditionsDr Rajat Bhattacharyya KK Women’s and Children’s Hospital, Singapore

ChairpersonAssoc Prof Dr Azlan HusinUniversiti Sains Malaysia, Kelantan, Malaysia

Case-based discussion NK/T-cell LymphomaProf Dr Kwong Yok Lam Queen Mary Hospital, Hong Kong

CNS LymphomaDr Jerome Tan Tsen Chuen Ampang Hospital, Selangor, Malaysia

Lymphoblastic LymphomaProf Dr Kwong Yok Lam University of Hong Kong, Hong Kong

Post Transplant Lymphoproliferative DisordersDato’ Dr Chang Kian Meng Sunway Medical Centre, Selangor, Malaysia

0930 - 1000 Panel discussion Panel discussion

1000 - 1015 BREAK

1015 - 1140Session 2.A:

How To Improve Transplant Outcome? (Case-based)

Session 2.B: How I Treat (Leukaemia)? (Case-based)


How To Improve Transplant Outcome in Acute Myeloid Leukemia (AML)?Assoc Prof Dr Koh Liang Piu National University Cancer Institute, Singapore

Reducing Toxicity of Stem Cell Transplant in Acute Lymphoblastic Leukaemia in ChildrenDr Rajat Bhattacharyya KK Women’s and Children’s Hospital, Singapore

Improving Allo-HCT in AAAssoc Prof Dr Nada Hamad Kinghorn Cancer Centre, New South Wales, Australia

Improving Allogeneic Stem Cell Transplant Outcomes in MyelofibrosisAssoc Prof Dr Nada Hamad Kinghorn Cancer Centre, New South Wales, Australia

ChairpersonDr Muhd Zanapiah ZakariaPrince Court Medical Centre, Kau Malaysia

Management of FLT3m AMLAssoc Prof Dr Naval Daver MD Anderson Cancer Center, Texas, United States

Personalized Induction and Maintenance Approaches for AML Assoc Prof Dr Naval Daver MD Anderson Cancer Center, Texas, United States

1115 - 1130: Panel discussion with Assoc Prof Naval Daver

1130 - 1155:T-cell Acute Lymphoblastic Leukaemia Dr Abu Dzarr AbdullahUniversiti Sains Malaysia, Kelantan, Malaysia

1155 -1210: Panel discussion Dr Abu Dzarr Abdullah

1140 - 1210 Panel discussion

1210 - 1310 SATELLITE SYMPOSIUM 3 SATELLITE SYMPOSIUM 4

ChairpersonDr Viknesh NaiduSanofi, Selangor, Malaysia

Prevention Strategies for VTE in Medical ill PatientsProf Dr Roopen Arya King’s College Hospital, London, United Kingdom

Clinical Practice and Guideline Recommendation to Prevent VTE in Surgical PatientDr Henning Loo Cheng Kien Sunway Medical Centre Velocity, Selangor, Malaysia

ChairpersonDr Gan Ee LengHospital Tuanku Ja’afar, Negeri Sembilan, Malaysia

Cell Signaling Regulations with Jakavi to Optimise Myelofibrosis TreatmentProf Martin Griesshammer Johannes-Wesling Clinic Minden, Minden, Germany

1310 - 1400 BREAK

1400 - 1520Session 3.A:

Cancer Cellular Immunotherapy(Principles, Applications, Pitfalls)

(Case-based)

Session 3.B: Transplant Laboratory

(Case-based)

Symposiums


Presentations



Dendritic Cell (DC) Therapy: Concepts Dr Kenichiro Hasumi ICVS Tokyo Clinic, Tokyo, Japan

HITV Therapy: Clinical Case ReportsDr Kenichiro Hasumi ICVS Tokyo Clinic, Tokyo, Japan

Bi-specific Antibodies in Acute Lymphoblastic LeukaemiaProf Dr Renato Bassan Ospedale dell’Angelo, Mestre-Venezia, Venice, Italy

ChairpersonAssoc Prof Dr Nurasyikin YusofHospital Canselor Tuanku Muhriz, Kuala Lumpur, Malaysia

HLA Typing and Donor Choice in Allogeneic HSCT - Does Everyone Now Have a Donor?Prof Dr John Moore St. Vincent’s Health Network, Sydney, Australia

Monitoring Post-Transplant (Chimerism)Prof Dr Raja Zahratul Azma Raja Sabudin Hospital Canselor Tuanku Muhriz, Kuala Lumpur, Malaysia

How to Diganose and Manage Tranfusion-Related Acute Lung InjuryProf Dr Erica Wood Monash University, Melbourne, Australia

Platelet Refractoriness Dr Nor Hafizah Ahmad National Blood Centre, Kuala Lumpur, Malaysia


1540 - 1550 BREAK

1550 - 1650 Debate 1 & 2 Session 4: Nurses: Transplant

Debate 1 : “MRD-Negative B-ALL Should be Transplanted in CR1”

ChairpersonDr Ho Kim WahAmpang Hospital, Selangor, Malaysia

Fertility Preservation Among Haematopoietic Cell Transplant (HCT) RecipientsDr Lavitha Sivapatham Ampang Hospital, Selangor, Malaysia

Patient Registry Systems in Haematology in MalaysiaDr Lew Kian Nian Health Informatics Center, Planning Division, Ministry of Health, Kuala Lumpur, Malaysia

How to Improve the Quality and Stability of Apheresis Product for Haematopoietic Stem Cell TransplantDr Habsah Aziz Hospital Canselor Tuanku Muhriz, Kuala Lumpur, Malaysia

For : Assoc Prof Dr Wan Fariza Wan Jamaludin Pusat Terapi Sel, HCTM, Kuala Lumpur, Malaysia

Against : Dr Mohd Haris Fadzillah Abdul Rahman Subang Jaya Medical Centre, Selangor, Malaysia

Debate 2: “ ELN-Favourable-Risk AML Should be Transplanted in CR1”

For : Dr Lim Soo Min Sultanah Aminah Hospital,Johor, Malaysia

Against : Dr Toh See Guan Tuanku Ja’afar Hospital,Negeri Sembilan, Malaysia

ChairpersonDr Jay Suriar RajasuriarGleneagles Hospital, Kuala Lumpur, Malaysia

AdjudicatorDato’ Dr Vijaya Sangkar Pantai Hospital Bangsar, Kuala Lumpur, Malaysia

1650 - 1735 TEA SYMPOSIUM 1 TEA SYMPOSIUM 2

ChairpersonProf Dr Gan Gin GinUniversity of Malaya Medical Centre, Kuala Lumpur, Malaysia

Diffuse Large B-Cell Lymphoma (DLBCL) The Evolving Patient JourneyProf Dr Matthew J Matasar Memorial Sloan Kettering Cancer Centre. New York, United States

Dr Ng Soo Chin Subang Jaya Medical Centre, Selangor, Malaysia

ChairpersonDr Liew Hong KengHospital Sultanah Bahiyah, Kedah, Malaysia

Living with ITP (Immune Thrombocytopaenic Purpura): Patient to Person Approach Dr Drew Provan The Royal London Hospital, London, United Kingdom



1735 - 1900 MEET THE EXPERT 2 (MTE 2) (Case-Based)For delegate who registered for MTE only

Symposiums


Presentations


Group 1: How to Best Select a Haploidentical Donor? ChairpersonDr Muhd Zanapiah ZakariaPrince Court Medical Centre, Kuala Lumpur, Malaysia

Prof Dr Xiao-Jun Huang Peking University People’s Hospital & Institute of Hematology, Beijing, China

Group 2: How to Incorporate Measurable Residual Disease (MRD) In The Routine Clinical Practice of Acute Leukaemia Patients?ChairpersonDr Goh Kim YenKPJ Ampang Puteri Hospital, Selangor, Malaysia

Prof Dr Sylvie Freeman University of Birmingham, Birmingham, United Kingdom

Group 3: Managing Transfusion-Related Reactions and Multiple Alloantibodies and AutoantibodiesChairpersonProf Dr Raja Zahratul Azma Raja SabudinHospital Canselor Tuanku Muhriz, Kuala Lumpur, Malaysia

Dr Nor Hafizah Ahmad National Blood Centre, Kuala Lumpur, Malaysia

Group 4: Immunotherapies for Lymphoma: The Role of a Pathologist?ChairpersonDr Tengku Ahmad Hidayat Tengku K AzizBeacon Hospital, Selangor, Malaysia

Prof Dr Noraidah Masir Hospital Canselor Tuanku Muhriz, Kuala Lumpur, Malaysia

Group 5: Early Post-Transplant Complications and Nursing ManagementChairpersonDr Azizan SharifHospital Sultanah Aminah, Johor, Malaysia

Ms Julija SipaviciusRoyal North Shore Hospital, Sydney, Australia

End of Conference Day 2



Programme Detail - Day 311th August 2022 - Thursday


0800 - 0930 Session 5.A: CAR T-cell (Case-based)

Session 5:B: How Do I Diagnose? (Case-based)

Symposiums


Presentations



Factors Impacting Outcomes of CD19 CAR-T Cell Immunotherapy for B Cell MalignanciesProf Dr Cameron Turtle Fred Hutchinson Cancer Research Center, Washington, United States

Manufacturing & Infusion of CAR-T Cells- Focusing on the Local SettingMr Timothy Lim Say Wai Plutonet Sdn Bhd, Selangor, Malaysia

ChairpersonDr Wong Chieh Lee Sunway Medical Centre, Selangor, Malaysia

Graft-Versus-Host Disease (GvHD)Assoc Prof Dr Ikmal Hisyam Bakrin Universiti Putra Malaysia, Selangor, Malaysia

The Emerging Role of Circulating Tumor DNA Testing in CancersAssoc Prof Ir Ts Dr Mohd Ridzuan Ahmad Universiti Teknologi Malaysia, Johor, Malaysia

PET/CT Scans Interpretation After Immune and Cellular Therapy in Hematological MalignanciesDr Thanuja Mahaletchumy Hospital Canselor Tuanku Muhriz , Kuala Lumpur, Malaysia

How Do I Diagnose: Role of Molecular (Genetic) Testing in Acute Leukaemia- What is Relevant in 2022?Assoc Prof Dr Elizabeth Tegg ICPMR-NSWHP Westmead/University of Sydney, Sydney, Australia


1015 - 1030 BREAK

1030 - 1150 Debate 3 & 4Session 6:

Nurses Session -What Do the Haematology Nurses Need to Know?

Debate 3: BiTEs versus CAR-T for Relapsed Refractory B-ALL

ChairpersonDr Nor Saaidah Kamal RodinHospital Canselor Tuanku Muhriz, Kuala Lumpur, Malaysia

Palliative Care: What Do Nurses Need to Know?Dr Lam Chee Loong University of Malaya Medical Centre, Kuala Lumpur, Malaysia

Graft versus Host Disease (GVHD) Complication and TreatmentDr Tan Sen Mui Ampang Hospital, Selangor, Malaysia

Safe Handling of Cytotoxic Chemotherapy for Nurses Dr Birinder Kaur Sadu Singh Hospital Canselor Tuanku Muhriz, Kuala Lumpur, Malaysia

Infection in Haematopoietic Cell Transplant (HCT) RecipientsAssoc Prof Dr Ramliza Ramli Hospital Canselor Tuanku Muhriz, Kuala Lumpur Malaysia

Team BiTEs : Dr Ng Chin Hin Gleneagles Hospital Singapore, Singapore

Team CAR-T: Prof Dr S Fadilah Abdul Wahid Pusat Terapi Sel-UKM, Selangor, Malaysia

Debate 4: BiTES versus CAR-T for Relapsed Refractory DLBCL

Team BiTEs: Dr Ng Soo Chin Subang Jaya Medical Centre, Selangor, Malaysia

Team CAR-T: Dr Chen YunxinSingHealth Duke-NUS Blood Cancer Centre, Singapore

ChairpersonDr Jay Suriar RajasuriarGleneagles Hospital, Kuala Lumpur, Malaysia

AdjudicatorDato’ Dr Chang Kian Meng Sunway Medical Centre, Selangor, Malaysia


1210 - 1310SATELLITE SYMPOSIUM 5 SATELLITE SYMPOSIUM 6

ChairpersonDato’ Dr Chang Kian MengSunway Medical Centre , Selangor, Malaysia

Disease Management with CAR-T in Relapsed and Refractory DLBCL: From Pivotal Trials to Clinical Practice Asst Prof Dr Francesca Lim Singapore General Hospital, Singapore

Evolving Role of CAR T-cell Therapy in R/R DLBCLDr Chen Yunxin SingHealth Duke-NUS Blood Cancer Centre, Singapore

ChairpersonProf Dr Gan Gin GinUniversity of Malaya Medical Centre, Kuala Lumpur, Malaysia

Evolution of Treatment Paradigm and Practical Considerations in AML Patients Ineligible for Intensive ChemotherapyDr Robin Gasiorowski Macquarie University, Sydney, Australia

1310 - 1400 BREAK

Programme Detail - Day 311th August 2022 - Thursday


1400 - 1500Session 7.A:

Controversies/Challenges In Hematopoietic Stem Cell Transplantation (HCT) (Case-based)

Session 7.B: How I Treat (Mixed Bag)? (Case-based)

Symposiums


Presentations


ChairpersonAssoc Prof Dr Wan Fariza Wan JamaludinPusat Terapi Sel, HCTM, Kuala Lumpur, Malaysia

Optimizing Transplant Outcomes for Newly-diagnosed Multiple Myeloma Dr Daryl Tan Chen Lung Mount Elizabeth Novena Hospital, Singapore

Is There Still a Role for Autologous Stem Cell Transplantation in Follicular and Diffuse Large B-cell Lymphomas in the Era of Novel Theraphies?Dr Daryl Tan Chen Lung Mount Elizabeth Novena Hospital, Singapore

Autologous Hematopoietic Stem Cell Transplantion (ASCT) in LeukaemiaProf Dr Bee Ping Chong University of Malaya Medical Centre, Kuala Lumpur, Selangor

ChairpersonDr Azizan SharifHospital Sultanah Aminah, Johor, Malaysia

Primary Refractory Primary Mediastinal B-cell Lymphoma (PMBCL)Dr Henning Loo Cheng Kien Sunway Medical Centre Velocity, Kuala Lumpur, Malaysia

AL Amyloidosis Assoc Prof Dr Peter Mollee Princess Alexandra Hospital Amyloidosis Centre, Queensland, Australia

Approach to Management of Chronic Graft versus Host Disease (GVHD)Dr Sharifah Shahnaz Syed Abd Kadir Ampang Hospital, Selangor, Malaysia


1520 - 1530 BREAK

1530 - 1600 MSH Trainees Session Session 8:Regenerative Medicine

ChairpersonAssoc Prof Dr Azlan HusinUniversiti Sains Malaysia, Kelantan, Malaysia

Panelist:Why Choose Haematology as a Career?Dr Jameela SatharAmpang Hospital, Selangor, Malaysia

What Does It Take To Become a Qualified Clinical Haematologist in Malaysia? Dato’ Dr Goh Ai SimHospital Pulau Pinang, Pulau Pinang, Malaysia

Opportunities in Clinical Haematology PracticeDr Mohd Haris Fadzillah Abdul Rahman Subang Jaya Medical Centre, Selangor, Malaysia

ChairpersonDato’ Dr Badrul Akmal Hisyam Md. YusoffHospital Canselor Tuanku Muhriz, Kuala Lumpur, Malaysia

Ethical and Regulatory Aspects of Stem Cell Therapy in Malaysia: Where are We Now?Dr Mohammad Firdaus Abdul Aziz Faculty of Law, University of Malaya, Kuala Lumpur, Malaysia

Key Requirements Prior to Starting Stem Cell-Based Clinical TrialsMs Nik Syazana Izyan Saffery Cytopeutics Sdn Bhd, Selangor, Malaysia

MSC Clinical Applications in Ischemic and Degenerative Diseases: Focus on Stroke and DiabetesDr Chin Sze Piaw CMH Specialist Hospital, Negeri Sembilan, Malaysia

Induced Pluripotent Stem Cells - Applications In HaematologyEmeritus Prof Dr Cheong Soon Keng Universiti Tunku Abdul Rahman, Kuala Lumpur, Malaysia

1710 - 1740: Panel discussion


1615 - 1740 Haematology Quiz

Morphology & Flow Cytometry & Cytogenetics

Transfusion and Coagulation

HLA Typing

ChairpersonDr Lau Ngee SiangAmpang Hospital, Selangor, Malaysia

ChairpersonAssoc Prof Dr Asral Wirda Ahmad AsnawiUniversiti Sains Islam Malaysia, Negeri Sembilan, Malaysia

1740 - 1840

TEA SYMPOSIUM 3 TEA SYMPOSIUM 4

ChairpersonDr Ng Soo ChinSubang Jaya Medical Centre, Selangor, Malaysia

Optimizing First Line Therapy in Patients with Advanced Stage Classical Hodgkin’s Lymphoma Dr Anna Sureda Institut Català d’Oncologia-Hospitalet, Barcelona, Spain

ChairpersonDr Margaret YoongKite, a Gilead Company, Singapore

CAR T-Cell Therapy Patient Journey, from Data to the Real WorldDr Colin Phipps DiongParkway Cancer Centre, Singapore

1840 - 1900 PRIZE GIVING AND CLOSING REMARK

End of Conference Day 3

Date : 9 August 2022 (Tuesday)Time : 1650 - 1850

3 groups with 50 delegates per group. Each group will be given a virtual room. Focus group discussion on specific Issues in haematological patients.

Delegates: To prepare questions/cases to be discussed with the Expert prior to the session.

Group 1

Chairperson Dr Sivakumar PalaniappanHospital Canselor Tuanku Muhriz, Kuala Lumpur, Malaysia

COVID-19 Vaccination- Focus on Immunocompromised Host (ICH) Patients: Risk Versus Benefit?Dato’ Dr Suresh Kumar Chidambaram Sungai Buloh Hospital, Selangor, Malaysia

Chairperson Dr Sivakumar PalaniappanHospital Canselor Tuanku Muhriz, Kuala Lumpur, Malaysia

COVID-19 Problems and Possibilities in Haematological Diseases and Stem Cell Transplant?Dr Veena Selvaratnam Ampang Hospital, Selangor, Malaysia

Group 2 *Participants are encouraged to email the cases prior to the session to the Secretariat

(the speaker would like to review the cases first)

Chairperson Assoc Prof Dr Nurasyikin YusofHospital Canselor Tuanku Muhriz, Kuala Lumpur, Malaysia

Diagnosis and Management of VITT (Vaccine-induced Immune Thrombotic Thrombocytopenia) Prof Dr Christopher Ward Royal North Shore Hospital, Sydney, Australia

Chairperson Assoc Prof Dr Nurasyikin YusofHospital Canselor Tuanku Muhriz, Kuala Lumpur, Malaysia

Challenges in Anticoagulation Therapy in COVID-19 Patients with Underlying Haematological Conditions/Thrombocytopenia,CoagulopathyProf Dr Christopher Ward Royal North Shore Hospital, Sydney, Australia

Meet The Expert 1

ABSTRACTS

th


Organised by:

Date : 10 August 2022 (Wednesday)Time : 1735- 1900

5 groups (Each group with a maximum of 50 delegates. Participants to prepare questions for discussion.)

Delegates: To prepare questions/cases to be discussed with the Expert prior to the session.

Meet The Expert 2

Group 1

Chairperson Dr Muhd Zanapiah ZakariaPrince Court Medical Centre, Kuala Lumpur, Malaysia

How to Best Select a Haploidentical Donor?Prof Dr Xiao-Jun Huang Peking University People’s Hospital & Institute of Hematology, Beijing, China

Group 2

Chairperson Dr Goh Kim Yen KPJ Ampang Puteri Hospital, Selangor, Malaysia

How to Incorporate Measurable Residual Disease (MRD) in the Routine Clinical Practice of Acute leukaemia patients?Prof Dr Sylvie Freeman University of Birmingham, Birmingham, United Kingdom

Group 3

Chairperson Prof Dr Raja Zahratul Azma Raja SabudinHospital Canselor Tuanku Muhriz, Kuala Lumpur, Malaysia

Managing Transfusion-Related Reactions and Multiple Alloantibodies and AutoantibodiesDr Hafizah Ahmad National Blood Centre, Kuala Lumpur, Malaysia

Group 4

Chairperson Dr Tengku Ahmad Hidayat Tengku K AzizBeacon Hospital, Selangor, Malaysia

Immunotherapies for Lymphoma: The Role of a Pathologist?Prof Dr Noraidah Masir Hospital Canselor Tuanku Muhriz, Kuala Lumpur, Malaysia

Group 5

Chairperson Dr Azizan SharifHospital Sultanah Aminah, Johor, Malaysia

Early Post-Transplant Complications and Nursing ManagementMs Julija SipaviciusRoyal North Shore Hospital, Sydney, Australia

ABSTRACTS

th


Organised by:

CODE TITLE MAIN AUTHOR NAME

C1A REAL-WORLD STUDY OF END TYROSINE KINASE INHIBITOR CESSATION IN CHRONIC MYELOID LEUKAEMIA (EnTIC) IN MALAYSIA

SIEW LIAN CHONG

C2ANTIBODY RESPONSE POST-COVID-19 VACCINATION IN PATIENTS WITH CHRONIC MYELOID LEUKAEMIA WITH COMPARISON BETWEEN COMIRNATY AND CORONAVAC VACCINE

KUAN JEW WIN

C3AUTOLOGOUS CD19 CHIMERIC ANTIGEN RECEPTOR-T (CAR-T) THERAPY FOR RELAPSED/ REFRACTORY B-ACUTE LYMPHOBLASTIC LEUKAEMIA (B-ALL) PATIENTS- A PHASE II CLINICAL TRIAL IN MALAYSIA

S FADILAH ABDUL WAHID

C4CLINICAL OUTCOMES OF RELAPSED OR REFRACTORY DIFFUSE LARGE B CELL LYMPHOMA - A MULTICENTER REAL-WORLD STUDY IN MALAYSIA

S FADILAH ABDUL WAHID

C5 HAPLOIDENTICAL BONE MARROW TRANSPLANT – A PERSONAL SERIES OF 21 PATIENTS FROM A PRIVATE MEDICAL CENTER SOO-CHIN NG

C6 HYPERLEUKOCYTOSIS IN PEDIATRIC ACUTE LEUKEMIAS AT CHIANG MAI UNIVERSITY HOSPITAL RUNGROTE NATESIRINILKUL

C7 IMMUNE RESPONSE OF CHRONIC MYELOID LEUKEMIA PATIENTS TOWARDS SARS-COV-2 VACCINATION CHIN SUM CHEONG

C8IRON BURDEN AND ENDOCRINE COMPLICATIONS IN PATIENTS WITH TRANSFUSION-DEPENDENT THALASSAEMIA IN SARAWAK. A RETROSPECTIVE CROSS-SECTIONAL STUDY

CHOW LAI CHEE

C9LONG TERM TREATMENT OUTCOME OF MULTIPLE MYELOMA PATIENTS POST AUTOLOGOUS STEM CELL TRANSPLANTATION IN KLANG VALLEY HOSPITALS

CHIN SUM CHEONG

C10 MULTIPLE MYELOMA IN BORNEO SARAWAK MALAYSIA:A DECADE OF EXPERIENCE IN A SINGLE CENTER LEONG TZE SHIN

C11OUTCOME AND CLINICAL CHARACTERISTICS OF ADULT PATIENTS DIAGNOSED WITH ACUTE MYELOID LEUKAEMIA IN PENANG: A SINGLE CENTRE EXPERIENCE

CAROL GOH CHEW YUEN

C12OUTCOMES OF COVID-19 IN HAEMATOPOIETIC STEM CELL TRANSPLANT RECIPIENTS: A RETROSPECTIVE ANALYSIS IN A NATIONAL TRANSPLANT CENTRE IN MALAYSIA

ANDY TANG SING ONG

C13 PLASMA CELL MYELOMA AND HYPER COAGULABILITY TISHYA INDRAN

C14 PREVALENCE OF INVASIVE FUNGAL INFECTION IN HAEMATOLOGY PATIENTS IN A TEACHING HOSPITAL LIONG CHEE CHIAT

C15RISK FACTORS AND OUTCOME OF COVID-19 INFECTION IN HEMATOLOGICAL PATIENTS: A MULTICENTER RETROPECTIVE ANALYSIS IN MALAYSIA

SUI KEAT TAN

C16THE SARAWAK MYELOFIBROSIS EXPERIENCE (SAMY): DEMOGRAPHICS AND OUTCOME OF MYELOFIBROSIS PATIENTS IN SARAWAK, MALAYSIA

ANDY TANG SING ONG

C17THERAPEUTIC USE OF CONVALESCENCE PLASMA IN SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2) PATIENTS WITH HEMATOLOGICAL MALIGNANCIES IN HOSPITAL AMPANG

KULDEEP KAUR SARBAN SINGH

Best 17 Abstracts in Research (Clinical)

Abstracts in Research (Clinical)


C18ADVERSE EVENTS FROM SARS-COV-2 VACCINATION AMONG PATIENTS WITH CHRONIC MYELOID LEUKEMIA IN MALAYSIA

CHIN SUM CHEONG

C19CLINICAL, HAEMATOLOGICAL AND CYTOGENETIC PROFILE OF ADULT MYELODYSPLASTIC SYNDROME IN TEACHING HOSPITAL, A SINGLE-CENTRE STUDY

CHEE WENG YAN SABRINA

C20 COST OF TREATMENT FOR MYELOFIBROSIS PATIENTS IN MINISTRY OF HEALTH HOSPITALS IN SARAWAK ANDY TANG SING ONG

C21EPIDEMIOLOGY AND CLINICAL PROFILES OF CUTANEOUS GRAFT VERSUS HOST DISEASE IN ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION

WAN FARIZA WAN JAMALUDIN

C22FEASIBILITY AND SAFETY OF COLLECTION OF MONONUCLEAR CELLS FOR AUTOLOGOUS CHIMERIC ANTIGEN RECEPTOR-T (CAR-T) CELL THERAPY IN HAEMATOLOGIC MALIGNANCIES

DR. WINT WINT THU NYUNT

C23LONG-TERM CLINICAL OUTCOMES OF AUTOLOGOUS BONE MARROW MONONUCLEAR CELL IMPLANTATION IN PATIENTS WITH SEVERE THROMBOANGIITIS OBLITERANS

FARINA BINTI MOHAMAD YUSOFF

C24PERSISTENCE AND DECAY OF ANTI-SARS-COV2 IG G ANTIBODY RESPONSE POST BNT162B2 SARS-COV-2 ( PFIZER-BIONTECH, COMIRNATY) VACCINE IN PATIENT WITH VARIOUS HAEMATOLOGICAL CONDITIONS.

LOW PEI LING

C25PREVALENCE AND SPECIFICITY OF RBC ALLOIMMUNIZATION AMONG CHRONIC LIVER DISEASE PATIENT IN HOSPTAL UNIVERSITI SAINS MALAYSIA

SITI ZALEHA S ABDULLAH

C26REAL WORLD OUTCOME OF CHRONIC LYMPHOCYTIC LEUKAEMIA PATIENTS TREATED WITH VENETOCLAX IN HOSPITAL AMPANG, SELANGOR

JEROME TAN TSEN CHUEN

C27RED BLOOD CELL ALLOIMMUNIZATION AND AUTOIMMUNIZATION IN TRANSFUSION DEPENDENT THALASSEMIA: A SINGLE CENTRE RETROSPECTIVE REVIEW

KEE TAT LEE

C28RELATIONSHIP BETWEEN CELL NUMBER AND CLINICAL OUTCOMES OF AUTOLOGOUS BONE-MARROW MONONUCLEAR CELL IMPLANTATION IN CRITICAL LIMB ISCHEMIA

FARINA BINTI MOHAMAD YUSOFF

C29THE DISTRIBUTION OF BCR-ABL1 FUSION TRANSCRIPTS AND THE INCIDENCE OF BLASTIC TRANSFORMATION AMONG CML PATIENTS IN KELANTAN

NABIHAH BINTI MOHD SHAKRI

C30TREATMENT FREE REMISSION (TFR) IN CHRONIC MYELOID LEUKEMIA (CML) -A MALAYSIAN PRIVATE CENTER EXPERIENCE.

SOO-CHIN NG

C31UTILISATION OF THERAPEUTIC PLASMA EXCHANGE IN TREATING TRANSPLANT-ASSOCIATED THROMBOTIC MICROANGIOPATHY: A SINGLE CENTRE RETROSPECTIVE CROSS-SECTIONAL COHORT STUDY

WONG YIH SEONG

C32 VASOVAGAL REACTION AMONG BLOOD DONORS: PREVALENCE AND FACTOR ASSOCIATED NUR NASUHA IBRAHIM

Best 15 Abstracts in Research (Laboratory)


L1ASSOCIATION OF MANNOSE-BINDING LECTIN (MBL) GENE POLYMORPHISMS WITH IMMUNE THROMBOCYTOPENIA IN KELANTAN, MALAYSIA

MUHAMAD AIDIL ZAHIDIN

L2CHROMOSOMAL ABNORMALITIES IN CHRONIC LYMPHOCYTIC LEUKAEMIA PATIENTS TREATED IN HOSPITAL AMPANG, SELANGOR

JEROME TAN TSEN CHUEN

L3 CLOT WAVE ANALYSIS (CWA) PARAMETERS IN PATIENT WITH PROLONGED IMMOBILIZATION

ROSMANIZA MUHAMAT YUSOFF

L4COMPARISON STUDY ON VIABILITY AND RECOVERY OF CD34+ HAEMATOPOIETIC STEM CELLS CRYOPRESERVED WITH 5% AND 10% DIMETHYLSULFOXIDE (DMSO)

DR NUR ZAINURA BINTI MOHAMAD

L5CYTOGENETIC FINDINGS AND ITS CORRELATION WITH OVERALL SURVIVAL (OS) AND EVENT FREE SURVIVAL (EFS) IN PATIENTS WITH AML

QHASMIRA BINTI ABU HAZIR

L6CYTOPEUTICS® HUMAN UMBILICAL CORD MESENCHYMAL STEM CELLS (HUC-MSCS): CELL TRANSDUCIBILITY, IN VITRO INVESTIGATIONS AND BIODISTRIBUTION IN BALB/C MICE

MARINI BINTI MARZUKI

L7 DELINEATION OF THE MOLECULAR BASIS OF BORDERLINE HAEMOGLOBIN A2 IN MALAYSIAN POPULATION

NORAFIZA BT MOHD YASIN

L8DOWNREGULATIN OF HSA-MIR-548D-3P AND OVEREXPRESSION OF HOXA9 IN DIFFUSE LARGE B-CELL LYMPHOMA PATIENTS AND THE RISK OF R-CHOP-CHEMOTHERAPY RESISTANCE/DISEASE PROGRESSION

TING CHOO YUEN

L9 EXTENDED RBC PARAMETERS IN LATENT IRON DEFICIENCY AMONG BLOOD DONORS IN HOSPITAL USM

SIVANESAN SOCKALINGAM

L10FREQUENCY AND CLINICAL IMPLICATION OF ADDITIONAL CHROMOSOMAL ABNORMALITY IN ADULT PHILADELPHIA CHROMOSOME POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA

PHAN CHIN LEE

L11GENETICALLY ENGINEERED HUMAN UMBILICAL CORD-DERIVED MESENCHYMAL STEM CELLS EXPRESSING HUMAN INTERLEUKIN-12 INHIBIT LUNG ADENOCARCINOMA CELLS IN VITRO

GOH JIUNN JYE

L12 HUMAN HB G-MAKASSAR IN MALAYSIA; IS IT COMMON? EZALIA ESA

L13MOLECULAR INTERROGATION OF CHRONIC MYELOID LEUKAEMIA PATIENTS WHO FAILED SECOND GENERATION TYROSINE KINASE INHIBITOR USING NEXT GENERATION SEQUENCING

SIEW LIAN CHONG

L14 MOLECULAR LANDSCAPE OF CASES WITH BORDERLINE HBA2 LEVELS IN HOSPITAL CANSELOR TUANKU MUHRIZ

LAILATUL HADZIYAH BINTI MOHD PAUZY

L15THE HAEMATOLOGICAL, HAEMOSTATIC AND INFLAMMATORY MARKERS IN EARLY SEPSIS BASED ON SOFA SCORE

FAIRUZ BINTI AMIL

Abstracts in Research (Laboratory)


L16ASSOCIATION OF DENGUE WARNING SIGNS DURING FEBRILE PHASE WITH ROTATIONAL THROMBOELASTOMETRY, CORTISOL AND FERITIN

SYARIFAH SYAHIRAH SYED ABAS

L17

CHARACTERIZATION OF RED BLOOD CELL PARAMETERS IN SOUTHEAST ASIAN OVALOCYTOSIS (SAO) AND NON-SOUTHEAST ASIAN OVALOCYTOSIS (NON-SAO) WITH OR WITHOUT THALASSAEMIA/HAEMOGLOBINOPATHIES

IZZATUL IZZANIS ABD HAMID

L18DOES OBESITY INCREASE RISK OF IRON DEFICIENCY?: A PRELIMINARY STUDY ON THE CORRELATION OF CENTRAL OBESITY, RED CELL INDICES AND IRON PARAMETERS

WAN ASMUNI WAN MOHD SAMAN

L19GENETIC VARIANTS OF GLUCOSE-6-PHOSPHATE DEHYDROGENASE (G6PD) DEFICIENCY IN SOUTHEAST ASIAN COUNTRIES AND FUTURE DIRECTIONS OF GENOMIC MEDICINE: A REVIEW

MOHAMED AFIQ HIDAYAT BIN ZAILANI

L20IMMUNOPHENOTYPING IN THE DIAGNOSIS OF ACUTE UNDIFFERENTIATED LEUKEMIA AND MIXED PHENOTYPE ACUTE LEUKEMIA

SITI MAISARAH TERMITI

L21KRÜPPEL-LIKE FACTOR 1 (KLF1) GENE MUTATION AMONG ALPHA THALASSAEMIA: RESULT OF A SINGLE REFERRAL CENTRE IN MALAYSIA

TAYE ZHI LING

L22 MOLECULAR GENETICS OF ALPHA THALASSAEMIA IN SOUTH-EAST ASIA: A NARRATIVE REVIEW

SITI NURRAZAN BINTI ZULKIFLI

L23 ROLE OF RUNX1 IN PLASMA CELL DIFFERENTIATION IN MULTIPLE MYELOMA PATIENTS TANG TING FANG

L24SIGNIFICANCE OF ABERRANT EXPRESSION OF MYELOID MARKER IN CORRELATION OF CYTOGENETIC ABNORMALITY IN PATIENT WITH B-ACUTE LYMPHOBLASTIC LEUKAEMIA

MOHD FIKRI

L25 THE PROFILE OF CMV-SPECIFIC T CELL IMMUNE RESPONSES IN ALLOGENEIC HAEMATOPOIETIC STEM CELL TRANSPLANTATION NORFARAZIEDA HASSAN

L26 VARYING PHENOTYPE PROFILE OF HAEMOGLOBIN ADANA INTERACTIONS

DR GOWRISANKARI NAVARETNAM

L27VERIFICATION OF THE REFERENCE INTERVAL OF WHITE BLOOD CELL PARAMETERS OF NEUT-GI AND NEUT-RI AMONG THE LOCAL POPULATION.

HO SOOK FONG

Code Title MAIN AUTHOR NAME

CC 1A CASE REPORT OF ACQUIRED THROMBOTIC THROMBOCYTOPENIC PURPURA ASSOCIATED WITH COVID-19 INFECTION

LOW PEI LING

CC 2A CASE REPORT OF LEPTOMENINGEAL MYELOMATOSIS AND RAPID IMPROVEMENT WITH REGIMEN CONSISTING OF DARATUMUMAB, POMALIDOMIDE, VINCRISTINE, PROCARBAZINE, AND DEXAMETHASONE

KUAN JEW WIN

CC 3 ACUTE PROMYELOCYTIC LEUKEMIA DURING PREGNANCY WITH DIFFERENTIATION SYNDROME HO SOOK YEE

CC 4 AN UNUSUAL CASE OF SPURIOUS HYPERLEUCOCYTOSIS WU JIN TENG

CC 5AUTOLOGOUS STEM CELL TRANSPLANTATION IN YOUNG ADULT WITH SOFT TISSUE AND BONE SARCOMA – SINGLE CENTRE EXPERIENCE

MOHD YAZID ZAMRI

CC 6CASE REPORT: USE OF ARSENIC TRIOXIDE PLUS MANNITOL IN AN ACUTE PROMYELOCYTIC LEUKEMIA PATIENT WITH CENTRAL NERVOUS SYSTEM RELAPSE

TIONG CHIONG SENG

CC 7 FACTOR VII DEFICIENCY: A RARE DISEASE WITH EVEN “RARER” TREATMENT CHEW LEE PING

CC 8 FORGOTTEN BUT NOT DISAPPEARED: ERYTHROPOIESIS STIMULATING AGENT INDUCED PURE RED CELL APLASIA JEROME TAN TSEN CHUEN

CC 9HAEMOPHAGOCYTIC SYNDROME SECONDARY TO DISSEMINATED TUBERCULOSIS MASQUERADING AS DIFFERENTIATION SYNDROME IN A CASE OF APML POST ATRA-IDARUBICIN INDUCTION

BONG ZHAO SHENG

CC 10 HEPATIC LYMPHOMA CAMOUFLAGE AS LIVER ABSCESS GUANG YONG CHONG

CC 11 HEPATOSPLENIC T-CELL LYMPHOMA : A RARE BUT AGGRESSIVE DISEASE THAM YEA BING

CC 12 HYPEREOSINOPHILIC SYNDROME WITH CRADIAC INVOLVEMENT: A CASE REPORT JEEVAKANTHI RAJENDRAN

CC 13IT IS NOT ALWAYS THALASSEMIA - A CASE REPORT OF AUTOIMMUNE HAEMOLYTIC ANAEMIA IN A PATIENT WITH HAEMOGLOBIN LEPORE

TAN SWEE LOOI

CC 14 LONGITUDINAL EXTENSIVE TRANVERSE MYELITIS ; A RARE PRESENTATION OF DIFFUSE LARGE B-CELL LYMPHOMA DARSHYINI RAMANUJAM

CC 15 METHOTREXATE ACUTE ENCEPAHLOPATHY IN B LINEAGE ACUTE LYMPHOBLASTIC LEUKEMIA KAM HOO YIP

CC 16 PARANEOPLASTIC DEGENERATION IN HODGKIN LYMPHOMA AZHREEN FUAD MOHAMAD AZUDIN

CC 17 PARAPLEGIA IN ACUTE LYMPHOID LEUKEMIA: A CASE SERIES WONG TIEN GEN

CC 18 PITFALLS IN THE DIAGNOSIS OF A RELAPSED LYMPHOMA LEE BEE SUN

CC 19SUCCESS SERIES OF A RARE LEUKEMIC VARIANT- BPDCN(BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM) -A SINGLE CENTRE EXPERIENCE

KHAITERI RAGHUNATHAN

CC 20SUCCESSFUL TREATMENT OF DISSEMINATED FUSARIUM INFECTION WITH ENDOPHTHALMITIS IN A PATIENT WITH ACUTE MYELOID LEUKEMIA

LEE ZHI YUAN

Case Series / Case Report (Clinical)

Case Series / Case Report (Laboratory)

Code Title MAIN AUTHOR NAME

CL1A RARE CASE OF CO-INHERITANCE HAEMOGLOBIN CHARLIEU [α106(G13) Leu →Pro (α2)] WITH SOUTH EAST ASIAN OVALOCYTOSIS

NURUL HIDAYAH BINTI MUSA

CL2A RARE CASE OF PARA-BOMBAY A ASSOCIATED WITH ANTI-H, ANTI-MIA AND POSSIBLE ANTI-M1 IN AN UNIVERSITY HOSPITAL

EVELYN TENG MEI YUONG

CL3 A RARE CASE OF T ACUTE LYMPHOBLASTIC LEUKAEMIA (T-ALL) WITH MINOR BCR::ABL1

SITI SHAHRUM MUHAMED SAID

CL4CASE SERIES : THE MOLECULAR LANDSCAPE OF CHRONIC MYELOID LEUKAEMIA PATIENTS EXPERIENCING TREATMENT-FREE REMISSION FAILURE

SIEW LIAN CHONG

CL5COLD AGGLUTININ (CA) - ASSOCIATED LYMPHOPROLIFERATIVE DISEASE (LPD), A NEW DISEASE ENTITY

FATIN ADLIA BINTI ARIFIN

CL6 EBV POSITIVE DLBCL-A RARITY HARI PRIYA RAGHVAN

CL7 FANCONI ANEMIA FROM A NOVEL MUTATION DETECTED BY WHOLE EXOME SEQUENCING: A CASE REPORT

RUNGROTE NATESIRINILKUL

CL8LOW PULSE OXIMETER READINGS IN A GIRL WITH UNSTABLE HAEMOGLOBIN KÖLN [GTG→ ATG, VAL→ MET]: A CASE REPORT

RUZANAZ SYAFIRA RUZMAN AZLEE

CL9 MAST CELL LEUKEMIA ANNIE SOUTI

CL10PSEUDOTHROMBOCYTOSIS DUE TO RED CELL FRAGMENTATIONS IN A PREGNANT LADY WITH HBH DISEASE MASQUERADING AS MYELOPROLIFERATIVE NEOPLASMS:A CASE REPORT

TAN JIE EN

CL11 SYSTEMIC MASTOCYTOSIS IN A CASE OF ACUTE MYELOID LEUKEMIA ASSOCIATED WITH T(8;21) FATIN ADLIA BINTI ARIFIN

CL12UNUSUAL CASES OF HAEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (HLH) COMPLICATING APLASTIC ANAEMIA (AA), A POSSIBLE ASSOCIATION?

CHEE WENG YAN SABRINA


Ab

stract - C

linica

l Resea

rch

Ab

stract - C

linica

l Resea

rch

c1

A REAL-WORLD STUDY OF END TYROSINE KINASE INHIBITOR CESSATION IN CHRONIC MYELOID LEUKAEMIA (EnTIC) IN MALAYSIA

Siew Lian Chong1, Asral Wirda Ahmad Asnawi1, 2, Tien Gen Wong1, Ahmad Zakiyy Mohamed1, Yea Bing Tham1, Nur Aini syakirah AS1, Sharifah Shahnaz Syed Abd Kadir1, Tee Chuan Ong1, Jerome Tan1, Kim Wah Ho1, Ngee Siang Lau1, Veena Selvaratnam1, Sen Mui Tan1, Dato’ Ai Sim Goh3, Ching Soon Teoh3, Sui Keat Tan3, Soo Min Lim4, Azizan Sharif4, Yang Liang Boo4, Chin Keong Christopher Liam4, Ahlam Naila Kori5, See Guan Toh6, Ee Leng Gan6, Si Yuan Ng7, Jenq Tzong Tan8

1Department of Hematology, Hospital Ampang, Selangor, Malaysia.2Faculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia, Negeri Sembilan, Malaysia.3Department of Hematology, Hospital Pulau Pinang, Pulau Pinang, Malaysia.4Department of Hematology, Hospital Sultanah Aminah Johor Bahru, Johor, Malaysia.5Department of Medical, Hospital Tengku Ampuan Afzan, Kuantan, Malaysia.6Department of Medical, Hospital Tuanku Jaafar, Negeri Sembilan, Malaysia.7Department of Medical, Hospital Melaka, Melaka, Malaysia.8Department of Medical, Hospital Taiping, Perak, Malaysia.

[email protected]

Background: The practice of indefinite tyrosine kinase inhibitor (TKI) provision for Chronic Myeloid Leukaemia (CML) has remained unchallenged. Furthermore, the ability of TKIs to eradicate the CML clone is still largely unknown. A multicentred observational study involving major hospitals in Malaysia to observe the clinical practise to End TKI in CML (EnTIC) was performed. The goal of this study was to determine the molecular response to TKI cessation in CML patients by close monitoring of BCR-ABL1.

Materials and Methods: Patients who received their first line TKI (Imatinib, Nilotinib or Dasatinib) for at least 4 years and achieved major molecular response of MR4 (IS:0.01%) with undetectable BCR-ABL1 transcripts for the two preceding years were recruited. Close clinical and molecular monitoring was performed with monthly BCR-ABL1 molecular analysis. Quantification of the BCR-ABL1 transcript was performed using real-time polymerase chain reaction. To date, the study has observed 80 patients from January 1st to December 31st, 2021.

Results: This interim analysis reported the outcome of 80 patients with a follow-up period of 12 months. Twenty-one patients (26.3%) experienced a molecular relapse defined as the loss of a major molecular response (MMR). Relapses occurred after a median time of 3 months (range: 1-8 months). Fifty-nine (73.7%) patients have since been in molecular remission with the longest remission duration achieved is 12 months. During the treatment-free phase, no progression towards advanced phases of CML occurred, and all relapsed patients regained MMR after restarting therapy.

Discussion & Conclusion: The preliminary findings showed that cessation of TKI in patients who achieved deep molecular response appears promising, whereby treatment-free remission can be maintained safely. The patients will be continued to be followed-up. Further observation is necessary to better define conditions that warrant the use of second generation TKI therapy. Following this, we hope to develop a method/algorithm that reliably identifies candidate patients who would benefit from TKI discontinuation while safely maintaining treatment-free remission status.


Ab

stract - C

linica

l Resea

rch

c1 C2

ANTIBODY RESPONSE POST-COVID-19 VACCINATION IN PATIENTS WITH CHRONIC MYELOID LEUKAEMIA WITH COMPARISON BETWEEN COMIRNATY AND CORONAVAC VACCINE

Jew Win Kuan1, Cheng Siang Tan2, Anselm Ting Su3, Vaenessa Noni2, Whilemena Upam Herman Ulok Melina4, Ummi Syafiqah Abdorahman4, Joseph Niler Bimbang4, Lela Su’ut4, Asri Said1

1Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak, Sarawak, Malaysia; 2Department of Para-clinical Sciences, Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak, Sarawak, Malaysia; 3Department of Community Medicine and Public Health, Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak, Sarawak, Malaysia; 4Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak, Sarawak, Malaysia

[email protected]

Background: Chronic Myeloid Leukaemia (CML) is a type of myeloproliferative neoplasm characterised by an oncogenic fusion gene, BCR-ABL1. Most CML patients present at chronic phase, ~90%1, when BCR-ABL1 tyrosine kinase inhibitor (TKI) is the recommended first line treatment. Antibody response after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination in CML patients is concerned due to probable CML-induced and/or TKI-induced immunosuppression. To our knowledge, two studies reported antibody response post-SARS-CoV-2 vaccine in CML patients2 ,3. A study reported anti-spike SARS-CoV-2 IgG (IgG-S) responses > 14 days after a dose of Comirnaty (ComirnatyTM or BNT162b2, Pfizer-BioNTech) (n=1) or ChAdOx1 (ChAdOx1 nCoV-19 or AZD1222, AstraZeneca-Oxford) (n=11) vaccine.2 Seroconversion rate post-ChAdOx1 was lower than control group, 8/11 (73%) versus 58/63 (92%).2 A study reported response three weeks after a dose of Comirnaty (n=16) using a different laboratory methodology.3 As data is little and less so on CoronaVac (CoronaVacTM, Sinovac) vaccine in CML patients, we conducted a longitudinal study on antibody progression post-SARS-CoV-2 vaccination in CML patients from southern Sarawak. We present the comparison of antibody response at W6 and W16 between Comirnaty and CoronaVac vaccine in the cohort.

Materials & Methods: Titre of IgG-S were determined prior to vaccination (W0) and at three (W3), six (W6), 16 (W16), 32 (W32) and 52 weeks (W52) in reference to the first dose of vaccination. The second dose of vaccine was the same vaccine type as the first dose, and it was scheduled at three weeks after the first dose for both vaccines. Vaccines was under Malaysia vaccination programme and generally type of vaccine was not decided by patients. Results: A total of 43 CML patients were enrolled from 26-Aug-2021 to 30-Nov-2021. Results presented was until 9-Dec-2021. At study entry, 23 (53%), 11 (26%), 2 (5%), 1 (2%), 2 (5%) patients were on imatinib, nilotinib, dasatinib, bosutinib, and ponatinib, respectively, 1 (2%) patient on imatinib+peginterferon-α due to concomitant CML and essential thrombocythaemia, and 3 (7%) patients were not on TKI as enrolled in Malaysia Stop TKI Trial (MSIT)4. Most of them had completed second dose of vaccine during study entry. At W6, seroconversion rate post-vaccination (IgG-S ≥ 50 AU/mL) was 42/43 (96.9%). The only non-seroconverted patient received ChAdOx1. After excluding patients with breakthrough COVID-19, median decline rate of IgG-S between W6 and W16 [(IgG-S W6 – IgG-S W16) / number of weeks between W6 and W16] was 165.2 (range -155.8 – 334.0) and 67.8 (31.1 – 222.41) AU/mL/week for Comirnaty (n = 6) and CoronaVac (n =7), respectively, (p = 0.029). Median of the percentage of decline rate [decline rate of IgG-S between W6 and W16 / IgG-S W6 x 100%] was 8.6%/week (-12.7% – 13.0%) and 9.2%/week (7.0% – 10.7%) for Comirnaty and CoronaVac, respectively, (p = 1.000).

Discussion & Conclusion: Our study showed high seroconversion rate post-vaccination in CML patients despite TKI. Comirnaty induced higher mean IgG-S than CoronaVac – 2007.3 (n=7) versus 698.5 AU/mL (n=14) (p=0.001) at W6 and 2237.0 (n=11) versus 252.2 AU/mL (n=9) (p=0.005) at W16, but similar percentage of IgG-S decline rate.


Ab

stract - C

linica

l Resea

rch

Ab

stract - C

linica

l Resea

rch

C3

AUTOLOGOUS CD19 CHIMERIC ANTIGEN RECEPTOR-T THERAPY FOR RELAPSED/ REFRACTORY B-ACUTE LYMPHOBLASTIC LEUKAEMIA PATIENTS- A PHASE II CLINICAL TRIAL IN MALAYSIA

S Fadilah Abdul Wahid1, Wint Wint Thu Nyunt2, Timothy Lim2, Mohd Razif Mohd Idris1, Muhd Zanapiah Muhd Zakaria1,3, Alex Chang H S4, Wan Fariza Wan Jamaludin1, Loh C-Khai5, Hamidah Alias5, Suria Abd Aziz6, Azlin Ithnin7, Seery Zaliza Azura1, Noraimy Abdullah1

1Pusat Terapi Sel (PTS), Faculty of Medicine, Hospital Canselor Tuanku Muhriz Universiti Kebangsaan Malaysia (HCTM UKM), Kuala Lumpur, Malaysia; 2Plutonet Sdn Bhd, Selangor, Malaysia; 3Prince Court Medical Center, Malaysia; 4Shanghai YaKe Biotechnology Ltd. School of Medicine, Tongji University; 5Department of Paediatrics, Hospital Pakar Kanak-Kanak UKM, Kuala Lumpur, Malaysia; 6Jabatan Perkhidmatan Makmal Diagnostik, HCTM UKM; 7Department of Pathology, HCTM UKM, Kuala Lumpur, Malaysia

[email protected]

Background: Autologous chimeric antigen receptor-T(CAR-T) therapy is a highly effective treatment for relapsed/refractory B-acute lymphoblastic leukaemia (r/r B-ALL). The success of CAR-T therapy is influenced by patient specific factors, treatment prior to cell infusion and CAR-T manufacturing processes. Hence, we embark on a study to evaluate the therapeutic potential of CD19-CAR-T cells manufactured locally.

This is a preliminary report of recruitment progress on an ongoing clinical trial and we report preliminary safety and efficacy data of patients who had received CAR-T infusion.

Materials and Methods: This prospective open label Phase II clinical trial is being conducted at PTS, HCTM UKM, over a 5-year period from January 2019 to January 2024 involving r/r B-ALL aged between 10 and 65 years. Safety and efficacy were assessed.

Results: A total of 20 patients were screened, only 12 were eligible. Eight patients were excluded because of CNS-3 leukaemia (n=1), rapid disease progression with poor performance status (n=2), newly diagnosed Human Immunodeficiency Virus infection (n=1), no detectable disease (n=2), life expectancy less than 3 months (n=1), failed assimilation test (n=1). Ten of 12 eligible patients underwent leukapheresis (two died before apheresis). Only 3 patients had CAR-T infusion, seven patients did not receive CAR-T cells because of disease progression/death (n=5) and manufacturing failure due to low CD3+ cell count (n=2).

We report the preliminary efficacy data of 3 patients who received single CAR-T infusion within September 2021 to March 2022. The median age at the time of infusion was 35 (range 22-43) years. All patients had haematopoietic stem cell transplantation (HSCT), with 2 allogeneic HSCT and 1 autologous HSCT. One patient received bridging chemotherapy and all patients had lymphodepleting chemotherapy. Viability and dose of CAR-T ranged from 80.6-93.6% and 1.2-2.5x106/kg, respectively. There was no grade ≥3 adverse event related to CAR-T cell therapy. Cytokine release syndrome occurred in 2 patients. No neurologic event occurred. Febrile neutropenia occurred in 2 patients. Response assessment at 1-month post CAR-T therapy showed complete remission with incomplete haematologic recovery with measurable residual disease (MRD) negativity by flow cytometry in 2 patients. One patient with molecular relapsed Ph-positive B-ALL achieved her bone marrow aspirate BCR:ABL1 (Minor) transcript at a level below the limits of quantitation at 3 months post CAR-T therapy. After a median follow up of 4 months (range 4-10), the median duration of response was not reached.

Discussion & conclusion: This preliminary report showed that (i) about half of patients referred for CAR-T clinical trial underwent leukapheresis and only a small proportion (15%) received CAR-T infusion and (ii) a single infusion of locally manufactured CAR-T cells was safe, feasible, and potentially efficacious for patients with r/r B-ALL. These encouraging observations will need to be confirmed with larger sample size and longer follow-up, and calls for implementation of measures to increase therapeutic potential of CAR-T such as early referral, better patient selection and timely leukapheresis and cell infusion.


Ab

stract - C

linica

l Resea

rch

C3 C4

CLINICAL OUTCOMES OF RELAPSED OR REFRACTORY DIFFUSE LARGE B CELL LYMPHOMA - A MULTICENTER REAL-WORLD STUDY IN MALAYSIA

Siti Nur Anikah Arshad1, Wint Wint Thu Nyunt2,3, Azimatun Noor Aizuddin4, Jerome Tan Tsen Chuen5, Wan Fariza Wan Jamaludin1,2, Sivakumar Palaniappan1, S Fadilah Abdul Wahid1,2

1 Department of Medicine, Faculty of Medicine, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; 2 Pusat Terapi Sel, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; 3 Plutonet Sdn Bhd, Selangor, Malaysia; 4 Department of Community Health, Faculty of Medicine, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; 5 Department of Hematology, Hospital Ampang, Selangor, Malaysia

[email protected]

Background: Relapsed or refractory diffuse large B cell lymphoma (RR-DLBCL) remains a significant cause of morbidity and mortality worldwide. To the best of our knowledge, this is the first published real-world data evaluating clinical outcomes of RR-DLBCL patients in Malaysia.

Objective: To determine the treatment response and survival rates of a large cohort of RR-DLBCL patients in Malaysia.

Materials & Methods: We retrospectively screened 1315 patients with Non-Hodgkin Lymphoma (NHL) diagnosed between January 2014 to December 2019 at two main haematology transplant centers in Malaysia, of which 670 patients were diagnosed with DLBCL, and 188 patients with RR-DLBCL were analyzed for clinical outcomes.

Results: Approximately 90.9% (609/670) of patients responded to first-line therapy, with 19.0% (127/670) of patients subsequently relapsed, while 9.1% (61/670) had primary refractory DLBCL. Among a total of 188 patients with RR-DLBCL, 64.9% (122/188) of patients received salvage chemotherapy (ST) with a response rate of 55.7% (68/122), of which only 41.0% (50/122) of patients received autologous stem cell transplantation (ASCT). The 5-year overall survival (OS) for all RR-DLBCL patients was only 24.1%, and 1-year progression-free survival (PFS) was 30.7%. ST group demonstrated significant benefit in RR-DLBCL compared to those without ST with a 5-year OS of 33.6% vs. 6.9% (HR of 0.38; 95% CI: 0.27-0.54; p<0.001). ASCT demonstrated significant benefit in RR-DLBCL compared to those without ASCT with a 5-year OS of 57.0% vs. 22.2% (HR of 0.32, 95% CI: 0.19-0.53; p<0.001). Poor Eastern Cooperative Oncology Group (ECOG) performance status with a high-risk International Prognostic Index (IPI) score were independent predictive factors of the inferior OS.

Discussion: The 5-years OS for all patients with RR-DLBCL and patients who did not receive ST and ASCT was very poor. ASCT remains an important treatment option for RR-DLBCL patients who achieved CR2. However, only 55.7% of patients responded to ST prior to ASCT, and 41.0% of patients were able to proceed to ASCT.

Conclusion: This large real-world data showed that the overall clinical outcomes among Malaysian population with RR-DLBCL patients remain poor, which are comparable worldwide. This represents unmet medical needs among RR-DLBCL patients, highlighting the urgent need to look for effective salvage therapy before ASCT and novel therapeutic strategies for patients who are ineligible for ASCT or relapse after ASCT.


Ab

stract - C

linica

l Resea

rch

Ab

stract - C

linica

l Resea

rch

C5

HAPLOIDENTICAL BONE MARROW TRANSPLANT – A PERSONAL SERIES OF 21 PATIENTS FROM A PRIVATE MEDICAL CENTER

Soo Chin Ng, ZH lim [email protected] Jaya Medical Center

BackgroundHaploidentical bone marrow transplant (Haplo BMT) has emerged as an important mode of BMT in recent years with advances made in overcoming the GVHD using post-transplant cyclophosphamide (PTCY).

Objectives To review the results of consecutive 21 HaploBMT done at SJMC.

Materials and methodsThe case records of the above patients were reviewed. The initial 2 years was a’ learning curve’ and only patients with relapsed and refractory (RR) cases were selected. Thereafter HaploBMT was performed for patients in complete remission (CR) and RR cases. Notably the number of cases significantly increased especially in the past 3 years. Post-transplant cyclophosphamide (PTCY) 40-50mg/kg was given on D3-4.

ResultsThe median age of twenty-one patients was 33.5 years (range: 17 - 59) and there were 15 females and 6 males. The median donor age was 27.5years (range 12-55). Nine patients in the initial years received TBI-based preparative regimen while the remainder 12 patients received the current regimen i.e., thiotepa/fludarabine/busulfex regimen. Twelve patients have acute leukemia (AML (7) and ALL (3) and hybrid leukemia (2)) while 4 patients have Myelodysplastic syndrome and one patient has transformed myelofibrosis. Four patients with non-Hodgkin’s lymphoma (3 T lymphoma and 1 refractory B cell lymphoma). Neutrophils and platelets recovered at a median of 15 days (Range: 12 – 23) and 19 days (range:11 - 78) respectively. CMV activation was noted in 17 patients while one patient who was on letermovir did not have CMV infection. The cumulative incidence of aGVHD grade II to IV at D100 was 47.6% (10/21) while the cumulative incidence of cGVHD at D100 was 19% (4/21) Five patients were given Ruxulitinib for treatment of GVHD; one patient died of grade IV GVHD. The median follow -up duration was 8 months with range of 0.2-39 months. Overall, there were 6 deaths out of 21 patients. The cause of death was failure of engraftment (2) relapse/refractory disease (3) and acute GVHD (1). The TRM (transplant related mortality) was 14% (3/21). For patients transplanted in in CR (complete remission) status -12 out of 13 patients (92%) are alive while patients in RR (relapse /refractory) status only 2 out of 5 were alive (40%).

DiscussionHaploBMT in this personal series showed encouraging results especially for patients transplanted in CR status. The time of platelet and neutrophil engraftment were acceptable. There are challenges encountered including 1) high DSA (donor specific antibodies) which contributed to non-engraftment despite plasma exchanges, rituximab and IVIG. 2) high rate of CMV activation in most cases warranted treatment. The GVHD rate and severity appeared to be manageable.

ConclusionsHaploBMT is a BMT modality that is gaining traction and the ease of getting donors in good time make BMT a reality for many patients. There is further refinement to be made to optimize the outcome for Haplobmt patients.


Ab

stract - C

linica

l Resea

rch

C6

HYPERLEUKOCYTOSIS IN PEDIATRIC ACUTE LEUKEMIAS AT CHIANG MAI UNIVERSITY HOSPITAL1Supavit Jirawattanapong, 1Napatsorn Kraivisitkul, 1Sarawut Kasemsook, 1Thapanat Rattanasri, 1Norapon Laisupanwong, 1,3Kanda Fanhchaksai, 1,2Rungrote Natesirinilkul

Affiliations 1Faculty of Medicine, 2Department of Pediatrics, Chiang Mai University Hospital, 3Research Cluster of Thalassemia and Red Blood Cell Disorders, Chiang Mai University, Chiangmai, Thailand

[email protected]

Background: Hyperleukocytosis, defined by initial white blood cell > 100,000/cu.mm, is one of emergency conditions in pediatric patients with newly-diagnosed or relapsed acute leukemia. It is sometimes concomitantly found with tumor lysis syndrome (TLS) and coagulopathy which may increase mortality. Most evidences of hyperleukocytosis were reported in adult patients with acute leukemia, however, the data of hyperleukocytosis in Thai pediatric patients are limited. The objectives of this study were to find the incidence of hyperleukocytosis and the association between hyperleukocytosis, TLS, coagulopathy and outcome in pediatric acute leukemia.

Material and Methods: A retrospective study was done in 175 patients, aged 0-16.6 years, who had newly-diagnosed or bone marrow-relapsed acute leukemia and admitted to Chiang Mai University (CMU) Hospital between January 2011 and December 2020. The demographic and clinical data, including age, sex, laboratory parameters during the first week of induction chemotherapy, management and outcome were retrieved from electronic medical records. Adverse events including TLS and coagulopathy and mortality were compared between hyperleukocytosis and non-hyperleukocytosis group. The statistically significant was accepted when P-value < 0.05.

Results: The total 175 patients with all 214 events were enrolled. 62.1% of events were male with the mean age (± standard deviation, SD) 6.11±4.28 years. Most of patients had newly-diagnosed acute lymphoblastic leukemia (ALL) (70.6%) followed by acute myeloid leukemia (AML) (28. 9%) and bone marrow-relapsed acute leukemia (18.2%). Hyperleukocytosis was found 12.6% (27/214) of all events including 11.2% of newly-diagnosed acute leukemia and 1.4% of relapsed acute leukemia. TLS was found 44.4% (12/27) and 9.1% (17/187) in hyperleukocytosis and non-hyperleukocytosis group, respectively (P < 0.01). Only 93 patients were investigated for prothrombin time (PT) and 92 were investigated for activated partial thromboplastin time (APTT), respectively. Prolonged PT was found 31.6% (6/19) and 14.9% (11/74) in hyperleukocytosis and non-hyperleukocytosis group, respectively (P = 0.09) while prolonged APTT was found 5.3% (1/19) and 5.5% (4/73) in hyperleukocytosis and non-hyperleukocytosis group, respectively (P = 0.97). Among all hyperleukocytosis events, most patients were managed by prompt chemotherapy and supportive care, only 25.9% (7/27) were initially treated with total exchange transfusion and none of the events was managed by leukapheresis. The mortality was found 22.2% (6/27) and 19.8% (37/187) in hyperleukocytosis and non-hyperleukocytosis group, respectively (P = 0.43).

Discussion and Conclusion: Hyperleukocytosis is commonly found in pediatric acute leukemia and is associated significantly for TLS, particularly in newly-diagnosed acute leukemia and relapsed acute leukemia. However, it is not associated with coagulopathy and mortality in this study.


Ab

stract - C

linica

l Resea

rch

Ab

stract - C

linica

l Resea

rch

C7

IMMUNE RESPONSE OF CHRONIC MYELOID LEUKEMIA PATIENTS TOWARDS SARS-COV-2 VACCINATION

Chin Sum Cheong1, Leh Ching Diana Ng2, Reena Rajasuriar1, Normala Arshad3, Nurul Syuhada Zulhaimi1, Boon Hong Kong4, Jamal I-Ching Sam5, Ping Chong Bee1, Gin Gin Gan1

1Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 2Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak, Sarawak, Malaysia; 3University Malaya Medical Center; 4Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 5Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

[email protected]

Background: SARS-CoV-2 vaccination has been the cornerstone to control the COVID-19 pandemic. Studies have shown that patients with hematological malignancy have higher risk of severe COVID-19 infection and demonstrate variable antibody response after vaccination. There are limited data on patients with hematological malignancies, particularly in this region. This study aims to compare the humoral responses of chronic myeloid leukemia (CML) patients against healthy subjects (HS) towards SARS-CoV-2 vaccination.

Materials and Methods: This is a cross-sectional study of CML patients receiving two doses of SARS-CoV-2 vaccine in a teaching hospital in Malaysia. Patients’ baseline demographic data were collected. Antibody titers against the receptor-binding domain (RBD) of the spike protein were measured using the quantitative Elecsys Anti-SARS-COV-2 S kits (Roche). Antibody titers at baseline (day 0) and 2 weeks after second vaccination were compared to that of HS. Seroconversion was defined as a ≥4-fold increase in antibody titer from baseline.

Results: Twenty-three CML patients and 8 HS were included but 4 CML patients were excluded due to previous infection and missing baseline antibody level. The majority of CML patients were male (68.4%), more than half (52.6%) were Chinese, followed by Malay (31.6%) and Indian (10.5%). HS comprised 75.0% Chinese and 25.0% Indian, majority being females (62.5%) (p=0.252 and p=0.206, respectively). Mean age upon immunisation was 48.3 years for CML patients and 41.6 years for HS (p=0.219). Most of the CML patients were on imatinib (72.2%), followed by nilotinib (22.2%) and dasatinib (5.6%). A majority of them were either in deep molecular response (55.6%) or in major molecular response (33.3%). Majority of CML patients (94.7%) and all HS received BNT162b2 mRNA vaccine. Mean antibody levels for CML patients and HS were 228.9U/ml and 239.4U/ml, respectively after second dose SARS-CoV-2 vaccination (p=0.679). All the CML patients and HS had seroconversion following second vaccination.

Discussion and Conclusion: Seroconversion rates of CML patients and HS are comparable. CML patients on tyrosine kinase inhibitor (TKI) are able to produce similar humoral responses towards SARS-CoV-2 vaccination.


Ab

stract - C

linica

l Resea

rch

C7 C8

IRON BURDEN AND ENDOCRINE COMPLICATIONS IN PATIENTS WITH TRANSFUSION-DEPENDENT THALASSAEMIA IN SARAWAK. A RETROSPECTIVE CROSS-SECTIONAL STUDY

Lai Chee Chow1, Bee Shuang Lee2, Zi Yang Lian1, Andy Sing Ong Tang3, Ee Wen Loh4, Say Chiew Ng5, Xin Yee Tan6, Muhammad Nooraiman Bin Ahmad Noordin7, Gek Bee Ong2, Lee Ping Chew1

1Haematology Unit, Department of Medicine, Sarawak General Hospital, Sarawak, Malaysia; 2Haematology Unit, Department of Paediatric, Sarawak General Hospital, Sarawak, Malaysia; 3Department of Medicine, Miri Hospital, Sarawak, Malaysia; 4Department of Medicine, Bintulu Hospital, Sarawak, Malaysia; 5Department of Medicine, Limbang Hospital, Sarawak, Malaysia; 6Department of Medicine, Sibu Hospital, Sarawak, Malaysia; 7Department of Medicine, Lawas Hospital, Sarawak, Malaysia

[email protected]

Background: Chronic transfusion remains the standard of care for patients with transfusion-dependent thalassemia(TDT). Apart from serum ferritin, magnetic resonance imaging using the T2* technique remains the golden standard to evaluate the severity of iron overload. The main purpose of this study is to assess the iron burden and endocrinopathies in patients with TDT.

Material & Methods: A retrospective, multicenter cross-sectional study of TDT patients aged 10 years old and above treated in Sarawak was conducted, between January 2019 and December 2019. Patients with serum ferritin >2500ng/ml, and liver iron concentration(LIC) ≥15mg/g were identified. For the analysis, descriptive statistics were used to describe the demographic data. Continuous variables were expressed as median and range. Categorical variables were calculated as frequencies and percentages. The association between two categorical variables was analyzed with a chi-square test or Fisher’s exact test. A p-value of ≤0.05 was considered statistically significant.

Results: Out of 89 patients, 60.7%(n=54) were males and 39.3%(n=35) were females with a median age of 21 years old (10.0-65.0). The median age of initiating blood transfusion was 1 year old (0.3-34.0 years). 75.3% (n=67) of the patients had beta-thalassemia major, 16.9% (n=15) had haemoglobin E/ beta-thalassemia and 7.9% (n=7) of the patients had beta-thalassemia intermedia (n=3), Hb Adana (n=1), HbH with HbE beta-thalassemia (n=1), beta-thalassemia Filipino with Hb Khon Kaen (n=1), Hb Constant Spring with beta-thalassemia intermedia (n=1). 97.7% (n=87) of the study population were on iron chelation therapy and 2.3% (n=2) of them were not on treatment. The most common endocrinopathies were short stature(n=46, 51.7%), followed by hypogonadism (n=24, 27%), delayed puberty(n=23, 25.8%), osteopaenia(n=18, 20.1%), hypothyroidism(n=10, 11.2%), diabetes mellitus(n=9, 10.1%), impaired glucose tolerance(n=6, 6.7%), osteoporosis(n=5, 5.6%) and hypoparathyroidism (n=3, 3.4%). Serum ferritin was statistically higher in patients with hypogonadism and hypoparathyroidism(p=0.02 and p=0.04, respectively), whereas LIC were statistically associated with hypogonadism and delayed puberty (both p<0.01). This study showed that the patients in 20-29 years old age group had a higher iron burden (p<0.01). Patients with 30 years old and above had a higher risk of developing at least one type of endocrine disorder(p=0.01). There was an association between patients on dual iron chelation therapy with serum ferritin >2500ng/ml and severe iron overload with LIC≥15mg/g (p<0.01).

Discussion & Conclusions: Our study shows endocrinopathy is common in our patients especially related to growth and puberty. Age 30 years and above is a significant clinical risk of developing endocrine disorder in our cohort, which is comparable to another study in Thailand that occurred at the of 25 years old and above. This demonstrates that endocrinopathies in TDT can be time-dependent, therefore this challenge can be overcome by early initiation and optimization of iron chelation therapy. The limitation of this study is that it is a retrospective study that may not be representative of the general population and is prone to selection bias. In conclusion, early detection of endocrine complications and prompt treatment are crucial to improve the morbidity and mortality of patients with TDT.


Ab

stract - C

linica

l Resea

rch

Ab

stract - C

linica

l Resea

rch

C9

LONG TERM TREATMENT OUTCOME OF MULTIPLE MYELOMA PATIENTS POST AUTOLOGOUS STEM CELL TRANSPLANTATION IN KLANG VALLEY HOSPITALS

Chin Sum Cheong1, Soo Chin Ng2, Ping Chong Bee1, Fui Min Edmund Chin1, Shasha Khairullah1, Chee Chiat Liong1, Mohd Yazid Zamri1, Kee Hean Alan Teh2, Mohd Haris Fadzillah Abdul Rahman2, Gin Gin Gan1

1Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 2Subang Jaya Medical Center, Selangor, Malaysia

[email protected]

Background: Autologous stem cell transplant (ASCT) has consistently shown to improve outcome of multiple myeloma (MM) patients. However, the role of ASCT is being questioned recently with the introduction of novel agents. Unfortunately, these novel agents are not easily accessible in developing nations such as Malaysia. This study aims to report on the long-term outcome of MM patients post ASCT in this new era of novel agents.

Materials and Methods: MM patients who were diagnosed between June 2001 and June 2020, and underwent ASCT in two hospitals were retrospectively studied. Patients’ demographic details and treatment details were included for analysis of progression free survival (PFS) and overall survival (OS).

Results: Eighty-five patients were included. The median age at presentation was 55 years old (ranged from 26 to 73 years old). More than half were Chinese (56.5%), followed by Malay (25.9%). IgG was the most common subtype (60%), followed by light chain disease (24.7%). Cytogenetic risk was determined for 44 patients, 9.1% was found to have poor risk. 28.8% of 52 patients belonged to Stage III based on International Staging System (ISS). Only 25.3% of patients achieved complete remission (CR) and 38.6% had very good partial response (VGPR) before ASCT. 58.8% of patients received maintenance therapy post ASCT. Median OS and PFS of patients after ASCT were 147 months and 40 months, respectively. Multivariate analysis showed that those in CR prior to ASCT compared to those in VGPR had significant better PFS (median PFS 73 months vs. 32 months, p=0.038). Poor cytogenetic risk adversely affected PFS (median PFS 10 months vs. 42 months, p=0.004) and OS (median OS 33 months vs. 147 months, p=0.029). Maintenance therapy post ASCT improved OS (median OS not reached vs. 79 months without maintenance, p=0.041).

Discussion and Conclusion: This study demonstrated that ASCT has still a role in improving outcome of MM patients. However, patients with adverse cytogenetic risk may benefit from newer therapies with the aim of achieving CR prior to transplant. Maintenance therapy post ASCT should be practiced for better outcome.


Ab

stract - C

linica

l Resea

rch

C9 C10

MULTIPLE MYELOMA IN BORNEO SARAWAK MALAYSIA: A DECADE OF EXPERIENCE IN A SINGLE CENTER

Tze Shin Leong1, Adelyn Fen Ein Tee1 , Grace Wan Chieng Lee1 , Lee Ping Chew1

1Haematology Unit, Medical Department, Sarawak General Hospital, Kuching, Malaysia

[email protected]

Background: Sarawak is the largest state of Malaysia situated on the island of Borneo. Sarawak General Hospital is the tertiary referral center of Sarawak (serving a population of 1 million people). It is 980 km away from its national hematology/transplant referral center in Kuala Lumpur, Malaysia, which is accessible only by air route. Hence, treatment of patients with multiple myeloma, especially consolidation with autologous stem cell transplant, in this part of the state is a big challenge due to its geographical constraint.

Materials and Methods: This is a retrospective study examining basic characteristics and clinical outcomes of multiethnic patients, diagnosed with multiple myeloma between 2010 and 2021 in Sarawak General Hospital. Patients’ case notes were traced and the relevant information was entered into a pre-designed data collection form. Data was analysed and interpreted via IBM SPSS Statistics version 27.0.

Results : There were a total of 149 patients with almost equal male to female ratio. The median age for patients was 62 years old (range 29 to 87 years old). Majority of them are local natives of Iban or Bidayuh descendants (n=67, 45.0%) followed by Malay (n=44, 29.8%) and Chinese (n=38, 25.2%). Most common type of multiple myeloma is of IgG variant (n=77, 52.0%). The most common myeloma related organ or tissue impairment (ROTI) is anaemia (n=120, 80.7%) followed by bone lesion (n=112, 75.3%), renal impairment (n=66, 44.5%) and hypercalcaemia (n= 45, 30.5%). More than half presented late with International Staging System - stage III disease (n=84, 56.7%). More than 80% (n= 123) has been treated with immunomodulary (ImiD) based eg. thamidomide or lenalidomide combination regime. Forty two patients (28.2%) received bortezomib based treatment such as VCD or VTD. Seven patients (n=7, 4.7%) have undergone high dose chemotherapy and autologous stem cell transplant.

Discussion & Conclusion: Based on a 10 year analysis from 2010 to 2019, eighty two patients died (n=82, 64.7%). Median survival time was 22 months). Two year overall survival (OS) was 48% and progression free survival (PFS) was 40.8%. Multivariate analysis showed age as the only independent predictor of OS. Patients with age more than 60 years old has a lower OS (HR 1.733, CI 1.06-2.84, p value= 0.03). There was a statistical improvement in terms of median overall survival, 12 months vs 17 months (p=0.012) comparing the year 2010 -2014 vs 2015-2019.

In conclusion, baseline characteristics of patients with multiple myeloma in Borneo Sarawak are similar to the rest of Asia. However, our median overall survival was comparatively lower to our counterparts. This could be due to reasons such as late presentation as a result of lack of awareness of disease; logistic and economic constraints that lead to poorer access to healthcare, including access to expensive but effective myeloma medication.


Ab

stract - C

linica

l Resea

rch

Ab

stract - C

linica

l Resea

rch

C11

OUTCOME AND CLINICAL CHARACTERISTICS OF ADULT PATIENTS DIAGNOSED WITH ACUTE MYELOID LEUKAEMIA IN PENANG: A SINGLE CENTRE EXPERIENCE

Carol Goh Chew Yuen1 , Tan Sui Keat1 , Chew Teng Keat1 , Chiang Su Kien1 , Goh Ai Sim1

1 Hematology Unit, Department of Medicine, Hospital Pulau Pinang, Penang, Malaysia.

[email protected]

Background: Acute Myeloid Leukaemia (AML) is challenging to treat owing to its heterogeneity. The objective of this study is to analyse the outcome and clinical characteristics of patients diagnosed with AML in our centre and to ascertain independent risk factors associated with inferior overall survival of AML patients.

Material & Methods: A retrospective analysis was performed for patients aged 15 to 59 years old diagnosed to have AML via bone marrow assessment between 1st January 2015 to 1st January 2021. Patients who refused or were unfit for chemotherapy and those with AML M3 were excluded. All of the patients were followed up till 31st March 2022. Statistical analysis was conducted using SPSS.

Results: We studied a total of 71 patients. The median age of presentation was 40 years with male to female ratio of 1.21. Majority were Malay (45.1%) followed by Chinese (42.3%), Indian (11.3%) and others (1.4%). Comorbidity was present in 32.4% of the patients while 8.5% had extra medullary involvement. The mean initial WBC was 60.29 x 109/L. 11.3% carried t(8,21) resulting in RUNXI-RUNXITI fusion transcript being the commonest molecular abnormality. The patients were risk stratified into favourable, intermediate and adverse risk group at 23.9%, 36.6% and 32.4% respectively. Majority of our patients (84.5%) received standard induction chemotherapy of ‘ 3+7’. A small proportion (16.9%) had secondary AML. 74.6% of patients achieved remission. 12.7% did not complete induction therapy. Our induction mortality rate was 2.8%. In spite of an initial remission, 35.2% (n=25) relapsed. Only 39.4% (n=28) underwent haematopoietic stem cell transplant (HSCT) in our study. Nineteen patients (26.7%) underwent Allogenic Stem Cell Transplant while nine patients (12.7% ) underwent Autologous Stem Cell Transplant as they did not have a HLA matched donor. Out of 28 transplanted patients,75% (n=21) are alive and 71.4% (n=20) of them remained in remission post HSCT. Disease free survival for subgroup of all remission patients was reported to be 40.6 months. HSCT significantly reduced hazard of death in comparison to patients who were non transplanted (HR 0.30, 95% CI 0.12, 0.72, p value= 0.007). Median survival time for those who underwent transplant was significantly prolonged at 57.5 months in contrast to 17.4 months median survival time for those who did not undergo HSCT.

Discussion & Conclusion: Significant independent risk factors associated with inferior overall survival of AML patients includes age >50 years, non standard induction other than ‘3+7’ chemotherapy, transplant ineligibility and induction failure. Presence of extra medullary involvement was not independently prognostic of survival in AML patients. In conclusion, HSCT markedly improves overall survival in AML patients and increased access to HSCT should be a priority.


Ab

stract - C

linica

l Resea

rch

C11 C12

OUTCOMES OF COVID-19 IN HAEMATOPOIETIC STEM CELL TRANSPLANT RECIPIENTS: A RETROSPECTIVE ANALYSIS IN A NATIONAL TRANSPLANT CENTRE IN MALAYSIA

Andy Sing Ong Tang1, Sui Keat Tan1, Sharifah Shahnaz Syed Abd Kadir1, Kim Wah Ho1, Ngee Siang Lau1, Jerome Tsen Chuen Tan1, Tee Chuan Ong1, Sen Mui Tan1

1 Haematology Department, Ampang Hospital, Malaysia

[email protected]

Background: Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome corona virus 2(SARS-CoV-2), was declared a pandemic by WHO in March 2020. Haematopoietic stem cell transplant (HSCT) recipients are more prone to develop severe infections due to immunocompromised state. We aimed to study the baseline characteristics and the outcome of our HSCT patients infected by COVID-19, and to identify the factors influencing the overall survival (OS).

Materials & Methods: This was a retrospective analysis performed in Ampang Hospital, Malaysia. We studied a cohort of HSCT with COVID-19 from April 2020 until April 2022. COVID-19 was classified as mild(no oxygen required with SpO2>95%), moderate(oxygen required with SpO2 90-95%), or severe(non-invasive or mechanical ventilation required with SpO2<90%). Quantitative real-time reverse transcriptase-polymerase chain reaction(qRT-PCR) or Antigen Rapid Test Kit(RTK-Ag) of nasal and/or oropharyngeal swabs were used to diagnose SARS-CoV-2 infection. Statistical analysis was conducted using SPSS(version 23.0; SPSS Inc.), and p<0.05 was considered statistically significant.

Results: Fifty patients (male 33; male-to-female ratio of 1.9) who underwent HSCT infected with SARS-CoV-2 were analyzed. The median age was 31 years(15-65) for allogenic, and 44 years(27-59) for autologous HSCT patients. The median time from HSCT to COVID-19 was 11.5 months (0-288) in allogenic and 16.5 months(1-79) in autologous recipients. At the time of COVID-19, 36(72%) were in complete remission, 4(8%) in partial remission and 10(20%) in relapsed/refractory status. Co-morbidities were present in 8(16%) patients. Fever was the most common presenting symptom–29(58.0%). Eight patients(16.0%) were asymptomatic at diagnosis. Eight patients(16.0%) received Favipiravir, one patient received Tocilizumab and two patients were given convalescent plasma therapy. Seven patients were admitted to intensive care unit with only one survivor. At the time of analysis, 8/50(16.0%) had died in which 3/8(37.5%) had refractory disease at time of COVID-19 diagnosis. The median time from COVID-19 to death was 18 days (2-108). The median follow-up from COVID-19 was 110.50 days(2-488). In univariate analysis, risk factors influencing overall survival in the total population were severity of COVID-19 infection (p < 0.001), performance status (p < 0.001), time from HSCT to COVID-19 (p = 0.022), types of HLA match (p < 0.001) and absolute lymphocyte count (p < 0.001). Looking more in detail on time from HSCT to COVID-19, the mortality rate in patients developing COVID-19 the first 6 months after HSCT was 35.7%(5/14) versus 8.3%(3/36) in those developing COVID-19 beyond 6 months from HSCT (p=0.018). Other factors such as age, vaccination status, types of transplant, conditioning regimen and graft-versus-host disease (GvHD) status at the time of COVID-19 did not significantly impact OS. In multivariate analysis, poor performance status (HR 47.53; 95% CI 4.38-515.33; p = 0.001) and higher severity of COVID-19 (HR 15.36; 95% CI 1.26-188.09; p = 0.033) increased the mortality risk.

Discussion & Conclusion: HSCT patients with severe COVID-19 infection and poor performance status have worse outcomes irrespective of type of transplant. The fact that COVID-19 resulted in high rates of mortality in post-transplant patients emphasizes the importance of infection prevention in this vulnerable group.


Ab

stract - C

linica

l Resea

rch

Ab

stract - C

linica

l Resea

rch

C13

PLASMA CELL MYELOMA AND HYPPERCOAGULABILITY

Tishya Indran1, Grigorios Gerotziafas2, Jawad Fareed3, Andrew Spencer4

1 Walter and Eliza Hall Institute, Melbourne, Australia; 2 Sorbonne Universite, Paris, France3 Loyola University Medical Centre, Maywood, United States;4 The Alfred Hospital, Melbourne, Australia

[email protected]@wehi.edu.au

Introduction: The malignant clonal cell proliferation in multiple myeloma is a result of significant immune dysregulation through clonal specific T cell expansion, elevated levels of CD4+ CD25+FOXP3+ T regulator cells, downregulation of NK cells, high levels of IL-6 and activation of immunosuppressive tumour associated macrophages (TAM) .

However, the mechanism in myeloma causing a hypercoagulable state, predisposing to venous thromboembolic (VTE) is unclear. Complicating disease factors coupled with immunomodulatory drugs (IMiDs) such as Lenalidomide, Thalidomide and Pomalidomide causing ubiquitination and degradation of the Ikaros Family Zinc Finger Protein (IKZF)1 and 3 by cereblon also contribute to the prothrombotic effect despite thromboprophylaxis.

Aims: The aim of this study was to analyse the changes in the coagulation profile and plasma cell disease burden with chemotherapy, including Lenalidomide in patients with multiple myeloma.

Methods: Coagulation profile and disease markers were retrospectively analysed in 16 clinical trial patients receiving treatment with Daratumumab, Lenalidomide and Dexamethasone (DRd) at The Alfred Hospital, Melbourne from April 2019 to August 2020. This study was approved by The Alfred Hospital ethics committee.Statistical analysis was performed using descriptive statistics and the Wilcoxon Sign Rank Test to compare the median coagulation profiles and disease markers after 1-2 cycles of DRd and 3-4 cycles of Drd. Biomarkers included Prothrombin Time (PT), Partial Thromboplastin Time (PTT), Fibrinogen, Thrombin Clotting Time (TCT), serum paraprotein (SPEP) and serum free light chain (SFLC) with a p value of <0.05 indicating statistical significance.

Results: A total 7 patients had coagulation profiles at the two time points i) post 1-2 cycles and ii) post 3-4 cycles of DRd. 9 patients had coagulation profiles only after 3-4 cycles of Drd. A separate analysis was performed using Wilcoxon Sign Rank with imputed median differences to allow the inclusion of the 9 additional patients subsequently increasing the sample size to a total of 16. All patients were on anticoagulation with aspirin (n=14), rivaroxaban (n=1) or clopidogrel (n=1) at the time of the analysis.

The analysis showed a statistically significant reduction in prothrombin time from median 13.6s (11.9-16.6) to 12.7 (11.7-14.1) with 3-4 cycles DRd in both analysis (p=0.006 and p= 0.027). Fibrinogen levels reduced from median of 5.4 (2.8-8) to 3.98 (2.3- 5.1) after 3-4 cycles (p=0.001). Serum paraprotein demonstrated statistically significant reduction from 10.8g/L (6 -13) to 7.6 g/L (2-13) after 3-4 cycles (p=0.007). Serum free light chains demonstrated reduction in median values from 82.8 (8.1 – 415.7) to 54.6 (0.8 – 338.6) but was not statistically significant (p=0.084).

Discussion: This study is different from previous research as all patients either responded to treatment or had stable disease after subsequent cycles of Daratumumab, Lenalidomide and Dexamethasone. It demonstrates a coagulation response to treatment in patients with high risk multiple myeloma. A larger study is required to confirm or refute these findings. However, this study has demonstrated that the hypercoagulable state in multiple myeloma improves with disease response.


Ab

stract - C

linica

l Resea

rch

C13 C14

PREVALENCE OF INVASIVE FUNGAL INFECTION IN HAEMATOLOGY PATIENTS IN A TEACHING HOSPITAL

Chee Chiat Liong1, Najihah Hussein1, Chin Sum Cheong1, Thevambiga Iyadorai2, Sun Tee Tay2, Rukumani D Velayuthan2, Gin Gin Gan1

1Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia2Department of Medical Microbiology, University of Malaya, Kuala Lumpur, Malaysia

[email protected]

Background: Invasive fungal infection (IFI) is a significant cause of morbidity and mortality among the patients with haematological malignancies. Patients who have acute leukaemias or those who requiring haematopoietic stem cells transplant will be at higher risks due to high intensity chemotherapy and prolonged neutropenia. Identifying IFI early is important in the treatment. However there is lack of data in Malaysia. Our study aims to identify the prevalence and possible risk factors of IFI in our patients with haematological malignancies.

Materials and Methods: This is a prospective study. Patients who were diagnosed with acute leukaemias or those who required haematopoietic stem cells transplant are recruited after consent obtained from June 2020 till May 2022. Clinical data were extracted from the hospital electronic medical record system. Criteria used to diagnose IFI were according to the revised European Organization for Research and Treatment of Cancer /Mycoses Study Group (EORTC/MSGERC) consensus 2020.

Results: A total of 81 patients with 128 admission episodes were included. The median age of the patients was 53 years old (range 17-75 years old). 48% of patients were female. Majority of the patients were Malay (46.1%) followed by Chinese (37.5 %), Indians (15.6 %) and others (0.8%). Most of the patients have peripherally inserted central catheter (82.8%). 90% of the patients are on antifungal prophylaxis. The most common haematological malignancy is acute myeloid leukaemia (AML) at 59.4%. There are 9 proven IFI cases, 1 probable case and 5 possible cases. These IFI were predominantly diagnosed in patients with AML (73.3%). Most of these patients (66.7%) with IFI also have neutropenia more than 10 days. 89% of the proven IFI were due to Candida spp. infection, and the remaining was due to Trichosporon asahii.

Discussion & Conclusion: The prevalence of all-category IFI in haematological patients in our center is 10.8%, consistent with other centres. However, the low prevalence of invasive mould infections may not be truly representative in this study as the biopsy rate is low. Patients were usually having severe thrombocytopaenia, therefore not able to proceed with invasive procedure. There is no significant association between IFI and the use of PICC and duration of neutropenia.


Ab

stract - C

linica

l Resea

rch

Ab

stract - C

linica

l Resea

rch

C15

RISK FACTORS AND OUTCOME OF COVID-19 INFECTION IN HEMATOLOGICAL PATIENTS : A MULTICENTER RETROSPECTIVE ANALYSIS IN MALAYSIA

Sui Keat Tan 1, Carol Chew Yuen Goh1 , Hong Siew Tan1 , Yi Lin Lee 8, Kuldeep Kaur 2, Pei Ling Low 2, Tze Shin Leong 3, Hock Hin Chuah 4, Ee Leng Gan 5, See Guan Toh 5, Gilbert Wilfred 6, Shan Shan Tan 6, Yang Liang Boo 7, Christopher Chin Keong Liam 7, Lily Lee Lee Wong 6, Lee Ping Chew 3, Tee Chuan Ong 2, Sen Mui Tan 2, Ai Sim Goh 1

1Hematology Unit, Department of Medicine, Hospital Pulau Pinang, Pulau Pinang, Malaysia; 2Department of Hematology, Hospital Ampang, Selangor, Malaysia; 3Hematology Unit, Department of Medicine, Hospital Umum Sarawak, Sarawak, Malaysia; 4Infectious Disease Unit, Department of Medicine, Hospital Umum Sarawak, Sarawak, Malaysia; 5Hematology Unit, Department of Medicine, Hospital Tuanku Jaafar, Negeri Sembilan, Malaysia; 6 Hematology Unit, Department of Medicine, Queen Elizabeth Hospital, Sabah, Malaysia; 7Hematology Unit, Department of Medicine, Hospital Sultanah Aminah, Johor, Malaysia; 8Centre for Clinical Trial, Institute for Clinical Research, Hospital Ampang, Selangor, Malaysia.

[email protected]

Background: Hematological patients as immunocompromised hosts are vulnerable to severe COVID-19 infection. Identification of adverse prognostic factors could assist hematologists to tailor appropriate treatment. We hereby report the outcome of COVID-19 infection in hematological patients and risk factors associated with severe infection and mortality.

Materials and Methods: This is a multicenter retrospective analysis of hematological patients with COVID-19 from 1st January 2021 to 31st December 2021. The variables assessed included baseline characteristics, type of hematological diseases, antineoplastic therapies, COVID-19 treatments and outcomes. Analyses were generated using R statistical software version 4.1.2. Prognostic factors were analysed using Cox proportional hazard regression analysis.

Results: A total of 300 patients (168 males, 132 females) were evaluated. The median age was 51 years (range: 15-85 years). 52% were 50 years old and above. 44% had at least one comorbidity. There were 153 (51%) lymphoid malignancies, 94 (31%) myeloid malignancies and 53 (18%) benign hematological disorders. Non Hodgkin lymphoma (26.6%) was the commonest hematological disease followed by acute myeloid leukaemia (16.3 %) and acute lymphoblastic leukaemia (9%). Of the 247 patients with malignancy, 55% patients had refractory disease. 104 (42%) patients were receiving intensive chemotherapy, 40 (16%) low intensity chemotherapy and 25 (10%) hypomethylating agent. 19% were undergoing B cell depleting monoclonal antibody based therapy. Only 8% had prior hematopoietic stem cell transplantation. 34.7% were fully vaccinated prior to COVID-19 infection. 45% developed severe COVID-19 infection (category 4 or 5). Cytokine release syndrome (37%) and organising pneumonia (33%) were the two commonest complications. The median follow up was 158 days (range: 4 - 345 days). The overall mortality rate was 31.7% with survival rate at 90 days of 68.3% (95% CI: 62.6 to 73.2). Poor prognostic factors identified in the multivariable cox regression included ECOG 2-4 (HR 2.78; 95 CI 1.81 to 4.28; p ≤ 0.001), non-vaccination (HR 3.10; 95 CI 1.88 to 5.11; p ≤ 0.001), absolute lymphocyte count (ALC) < 0.5 (HR 1.81; 95 CI 1.17 to 2.80 ; p=0.011) and age ≥ 50 (HR 1.92; 95 CI 1.22 to 3.04; p=0.004).

Discussion & Conclusion: 45% of hematological patients with COVID-19 had severe infection with mortality rate of 31.7%. Poor survival was correlated with older age (≥ 50 years old), poor performance status, severe lymphopenia and non-vaccination. Vaccination is effective in preventing mortality but not severe infection. Hence, antiviral drugs and monoclonal antibodies for early treatment and prophylaxis should also be considered for high risk patients and potential vaccine non-responders.


Ab

stract - C

linica

l Resea

rch

C16

THE SARAWAK MYELOFIBROSIS EXPERIENCE (SaMy): DEMOGRAPHICS AND OUTCOME OF MYELOFIBROSIS PATIENTS IN SARAWAK, MALAYSIA

Andy Sing Ong Tang1, Tze Shin Leong1, Qi Ying Wong2, Xin Yee Tan3, Ching Tiong Ko1, Kok Yew Ngew,4 Erik Kah Jin Teh5, Lee Ping Chew1

1Haematology Unit, Department of Medicine, Sarawak General Hospital, Malaysia; 2Department of Medicine, Miri Hospital, Malaysia; 3Department of Medicine, Sibu Hospital, Malaysia; 4RWE, CONEXTS, Novartis Corporation (Malaysia) Sdn Bhd; 5Medical Affairs, Novartis Corporation (Malaysia) Sdn Bhd

[email protected]

Background: Myelofibrosis(MF) is a rare disease with an annual incidence rate of 0.47 per 100,000 population. There is currently no published data reporting the demographics and outcome of MF patients in Sarawak. We report the real-world data of myelofibrosis in our state.

Materials & Methods: This non-interventional, retrospective study was conducted in Sarawak General Hospital, Sibu, Bintulu and Miri Hospital. All primary and secondary MF patients who met WHO 2016 diagnostic criteria, aged 18 years old and above at time of diagnosis, and diagnosed between January 2001 and 31 December 2021 were included. A data-derived Dynamic International Prognostic Scoring System(DIPSS)-plus risk categorization was determined for all patients at the time of diagnosis. All analyses were conducted using RStudio and p-value < 0.05 was considered as statistically significant.

Results: A total of 63 patients(male 31) with myelofibrosis were identified – 47(74.6%) primary MF and 16(25.4%) secondary MF. The median age for overall study population was 59.0 years old(33.0 to 93.0). Majority had high-risk [34/63(54.0%)] and intermediate-2 risk disease [19/63(30.2%)]. JAK2V617F mutation was identified in 52 patients(82.5%), followed by CALR mutation in 6(9.5%) and negative for both mutations in 5(7.9%). The combined annual incidence rate was 0.182 per 100,000 population. The period prevalence per 100,000 population over the entire study duration was 2.50. Patients with low and intermediate risks had higher haemoglobin level than high risk group (p <0.001). Hydroxyurea was used as first-line therapy in two-thirds of our patients – 41/63(65.1%), followed by interferon [8/63(12.7%)] and ruxolitinib [4/63(6.3%)]. Out of 46 patients who received second-line therapy, eighteen (39.1%) was switched to ruxolitinib and nine (19.6%) interferon. Ruxolitinib was used as third-line in five patients. Only one patient with high-risk disease underwent allogenic transplant. Hydroxyurea intolerance was reported in 4/41(9.8%), and hydroxyurea resistance in 9/41(22.0%). Half out of eight patients on first-line interferon were unable to tolerate due to side effects. Almost all patients tolerated ruxolitinib well, except one had upper respiratory tract and herpes zoster infection (both grade II). The median survival for overall patients was 6.8 years. Among low, intermediate-1 and intermediate-2 risk patients, the median 5-year survival had not been reached, whereas the median survival among high-risk patients was 4.88 years (p=0.0054). The use of ruxolitinib in myelofibrosis patients showed a better overall 5-year survival compared to no ruxolitinib arm, but the difference was not statistically significant (p=0.34). In the overall cohort, performance status and DIPSS+ risk category at time of MF diagnosis were identified as independent risk factors for mortality. Patients who had good performance status had lower hazard of death than patients who had poor performance status [HR (95% CI): 0.06(0.013-0.239), p <0.001]. Patients with intermediate risk disease had better OS compared to those in high-risk category [HR (95% CI): 0.24(0.082-0.695), p = 0.009].

Discussion & Conclusion: Hydroxyurea remains the most frequently used therapy in MF despite studies showing lower effectiveness than that of ruxolitinib. This registry provides a real-world overview of MF patients in our state and highlights key insight into the unmet clinical need.


Ab

stract - C

linica

l Resea

rch

Ab

stract - C

linica

l Resea

rch

C17

THERAPEUTIC USE OF CONVALESCENCE PLASMA IN SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2) PATIENTS WITH HEMATOLOGICAL MALIGNANCIES IN HOSPITAL AMPANG

Kuldeep Kaur 1, Noor Sheereen Binti Adzaludin2 Shubash Shander Ganapathy3 Wan Nurul Husna Binti Wan Alkamar Shah4 Ong Tee Chuan 1Faraizah Binti Abdul Karim 4Nor Hafizah Binti Ahmad 2 Veena Selvaratnam 1Suraya Hanim Binti Abdul Hashim5 Alif Adlan Mohd Thabit 5Noryati Binti Abu Amin2

1 Hematology Department of Hospital Ampang ;2 Pusat Darah Negara; 3 Public Health Institute Malaysia; 4

Hematopathology Department of Hospital Ampang ;5. Infectious Disease Unit of Hospital Ampang

[email protected]

Background : World Health Organization (WHO) had declared coronavirus disease 2019 (SARS-COV-2) a global pandemic in March 2020. Multiple trials have been conducted however treatment of disease remain elusive. Patients with hematologic malignancy (HM) represent a distinctive subset of patients caused by immune deficits in humoral and cellular immunity associated with both the diseases themselves and their treatments. Convalescent Plasma (CP) is a passive immunization strategy used to neutralize the virus and minimize the resulting inflammatory cascade and may benefit patient with underlying HM.

Objectives: This study was done to evaluate the outcomes and efficacy of CP in Covid-19 patient with HM in Hospital Ampang.

Materials and methods: This Pilot study included retrospective clinical data of SARS-COV-2 patients with HM from 1st January to 31st December 2021 hospitalized in Hospital Ampang. Data was collected from a retrospective period between 1st January to 30th June 2021 of patients who did not receive CP treatment, as control (non-CP) and compared to patients receiving CP from 1st July till 31st December 2021.

Results: A cohort of 91 HM patients with SARS-COV-2 hospitalized in Hospital Ampang were analyzed. 28 patients received CP treatment along with standard of care were compared with 63 patients (non-CP) who received standard of care treatment alone.

The median age in CP group was 36.5 (SD 18.54) years and non-CP group was 45 (SD 17.32) years. Duration of hospitalization was shorter in our CP group (16.5 days versus 20.5 days) although it was not statistically (p value =0.326). At 60 days all-cause mortality was 25% in the CP group and 40% in the non-CP group (p value =0.725). No association of mortality in both groups with baseline severity of illness, absolute lymphocytes count, disease status, age, co-morbid, Oxygenation status or previous Rituximab therapy.

Discussion: CP did not improve survival or outcomes of our patients.These results can be possible due to the low titer of the neutralizing antibody in the CP used in our study as the antibody titer was not measured. The efficacy of CP is likely to depend on the match between the strain specific transfused anti SARS-COV-2 antibody in donor plasma and the infecting virus variant in the recipient. A new strain was detected (B.1.1.7) which spread by January 2021 and CP used in this were collected in mid-year 2020.

However, CP infusion showed some improvement in C-Reactive Protein, Troponin-I level, oxygenation and ALC count in our patients at Day 7 of infusion suggesting inflammation and overreaction of immune system which is hallmark of COVID –19 infections was alleviated by antibodies in the CP.

Lesser patients required mechanical ventilation in CP group which might suggest benefits of CP in halting the progression of SARS-COV-2 infection although there were no survival benefits.

Conclusion: We observed that CP did not improve outcomes of HM patients who were infected with SARS-COV-2 Infection. Whether CP would benefit patients with HM and Covid-19, an adequately powered, randomized clinical trial with high titer of antibodies need to be conducted.

Keywords: SARS-COV-2 ,Hematological Malignancies, Convalescent Plasma


Ab

stract - C

linica

l Resea

rch

C17 C18

ADVERSE EVENTS FROM SARS-COV-2 VACCINATION AMONG PATIENTS WITH CHRONIC MYELOID LEUKEMIA IN MALAYSIA

Chin Sum Cheong1, Leh Ching Diana Ng2, Reena Rajasuriar1, Normala Arshad3, Nurul Syuhada Zulhaimi1, Boon Hong Kong4, Ping Chong Bee1, Gin Gin Gan1

1Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 2Faculty of Medicine and Health Sciences, Universiti Malaysia Sarawak, Sarawak, Malaysia; 3University Malaya Medical Center; 4Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

[email protected]

Background: Patients with hematological malignancies are at higher risk of severe COVID-19 infection. SARS-CoV-2 vaccines are important; however, monitoring for severe adverse events from immunization is crucial to ensure patient safety. This study aims to compare the side effect profile of chronic myeloid leukemia (CML) patients against healthy subjects (HS) towards SARS-CoV-2 vaccination.

Materials and Methods: A cross-sectional study on CML patients who received SARS-CoV-2 vaccine was performed in a teaching hospital in Malaysia. Patients’ baseline demographic data were collected. Side effects were self-reported 2 days after first and second vaccination, and were compared to that of HS.

Results: Twenty-two CML patients and seven HS were included. Majority of CML patients were male (63.6%), half (50.0%) were Chinese, followed by Malay (36.4%) and Indian (9.1%). HS comprise of 85.7% Chinese and 14.3% Indian, majority being female (71.4%) (p=0.168 and p=0.192, respectively). Mean age upon immunisation was 45.4 years old for CML patients and 44.3 years old for HS (p=0.709). Majority was on Imatinib (71.4%). 47.6% and 42.9% achieved deep molecular response and major molecular response, respectively. The two most common side effects reported by CML patients and HS after the first dose were pain at injection site (77.3% vs. 85.7%, p=1.000) and lethargy (50.0% vs. 28.6%, p=0.410). Other side effects include muscle ache (31.8% vs. 0.0%, p=0.147), headache (22.7% vs. 28.6%, p=1.000) and fever (18.2% vs. 0.0%, p=0.546). Similarly, 90.9% and 85.7% of CML patients and HS, respectively experienced pain at injection site after the second dose (p=1.000). Other side effects include lethargy (59.1% vs. 57.1%, p=1.000) muscle ache (45.5% vs. 42.9%, p=1.000), fever (36.4% vs. 42.9%, p=1.000) and headache (31.8% vs. 42.9%, p=0.665).

Discussion and Conclusion: CML patients experienced no major adverse events following two doses of SARS-CoV-2 vaccines, with rates similar to HS. Vaccination against COVID-19 is safe and is recommended for patients with CML on TKI.


Ab

stract - C

linica

l Resea

rch

Ab

stract - C

linica

l Resea

rch

C19

CLINICAL, HAEMATOLOGICAL AND CYTOGENETIC PROFILE OF ADULT MYELODYSPLASTIC SYNDROME IN TEACHING HOSPITAL, A SINGLE-CENTRE STUDY

WYS Chee1, PC Bee2, Mardziah M1

1Haematology Unit, Department of Pathology, Faculty of Medicine, University of Malaya; 2Division of Haematology, Department of Medicine, Faculty of Medicine, University of Malaya

[email protected]

Background: Myelodysplastic syndrome (MDS) encompassed a group of clonal haematopoietic disorders characterized by peripheral cytopenia, dysplasia and ineffective haematopoiesis. The condition harbored an increased risk of leukaemic transformation. Recurrent cytogenetic abnormalities have been described in about half of MDS patients and detection of certain chromosomal abnormalities were presumptive of the diagnosis in the absence of morphological dysplasia. The purpose of this study is to analyze the prevalence of cytogenetic abnormalities in adult MDS patients in UMMC and to correlate with their clinical characteristics and prognosis.

Materials & Methods: This retrospective study was based on 36 patients diagnosed with MDS in UMMC from January 2016 to December 2020. Demographics, haematological parameters and WHO subtypes of MDS were available in records. Cytogenetic analysis results at diagnosis were traced for all patients. Bone marrow cytogenetic testing was initially performed using the conventional G banding technique. Interphase FISH analysis was indicated for detection of chromosome 5, 7 and 20 abnormalities when there was no chromosomal abnormality detected by conventional cytogenetic. All patients were stratified by IPSS-R taken into consideration their haematological parameters and cytogenetic categories. Clinical prognosis was defined based on patients’ follow up records up to 1 year post diagnosis.

Results: MDS patients in our study ranged from 30-81 years old with a mean age of 65 years. They were predominantly male with a male:female ratio of 1.8:1. The most common subtype was MDS-MLD in 10 of 36 patients (27.8%). Chromosomal abnormalities were detected in 20 of 36 patients (55.6%) by combined Conventional Cytogenetic and FISH analysis. Single chromosomal abnormality was seen in 12 of 20 patients (60.0%), followed by complex karyotype in 6 patients (30.0%) and less commonly double abnormalities in 2 patients (10.0%). The most common single chromosomal abnormality in our patients was trisomy 8, seconded by del(7q). Half of our patients fall into the good cytogenetic category and with IPSS-R stratification, nearly one third were in the intermediate risk group. As for comparison between patients with normal and abnormal karyotype, platelet count was significantly lower in the abnormal karyotype group with a median count of 46 x 109/L (p = 0.011). Analysis also revealed a higher IPSS-R score in the abnormal karyotype group (p = 0.007). Otherwise, the two groups of patients do not differ much in terms of demographics, WHO subtypes or other haematological parameters including bone marrow blast count. Besides, our study has demonstrated a strong association between IPSS-R score and patients’ clinical outcome (p < 0.001).

Discussion & Conclusion: The prevalence of chromosomal abnormalities in our patients were similar to previous studies in Asian countries. As specific chromosomal abnormalities not only presumptive of the diagnosis of MDS, the impacts on prognosis and treatment decision were equally as important in the management of MDS patients.


Ab

stract - C

linica

l Resea

rch

C20

COST OF TREATMENT FOR MYELOFIBROSIS PATIENTS IN MINISTRY OF HEALTH HOSPITALS IN SARAWAK

Andy Sing Ong Tang1, Tze Shin Leong1, Adrian Tze Sung Goh2, Joyce Hong Ling Ong3, Lee Ping Chew1

1Haematology Unit, Department of Medicine, Sarawak General Hospital, Malaysia; 2RWE, CONEXTS, Novartis Corporation (Malaysia) Sdn Bhd; 3Value & Access, Novartis Corporation (Malaysia) Sdn Bhd

[email protected]

Background: Primary myelofibrosis is a rare type of myeloproliferative neoplasm with an annual incidence rate of 0.47 per 100,000. A real-world evidence (RWE) study was conducted to determine the disease evolution and costs of treatment for myelofibrosis (MF) patients managed in 4 Ministry of Health (MOH) hospitals in Sarawak.

Materials and Methods: The estimation of treatment cost was a planned analysis of the RWE study which included retrospective review of medical records of 63 adult MF patients treated in Sarawak General, Sibu, Bintulu and Miri Hospitals. The study was approved by Sarawak General Hospital HRRC and MREC. The current study was conducted to estimate the cost of out-patient visits, hospitalisation, transfusion and medication from the perspective of MOH. Out-patient visits and hospitalisation costs were calculated using current unit costs for full fee-paying patients to MOH hospitals. Transfusion costs were estimated for packed cell and platelet transfusions. Medication costs were calculated using drug prices from IQVIA database for MOH hospital sub-sector in 2021. Unit costs were standardised to index year of 2021.

Results: Analysis was able to be performed on all 63 medical records for outpatient and hospitalisation data while data from 61, 43 and 20 patients were analysable for 1st line, 2nd line and subsequent lines of medication. The mean number of out-patient visits was 6.13 visits per patient per year with an annual cost of RM367.80. Mean admission days was 9.47 days at a cost of RM3,030.40 per patient per year. There were 1.61 transfusions per patient per year where 84% of transfusions utilised packed cells and 16% with platelets. Assuming 2 pints of packed cell and 3 units of platelet per transfusion event, the annual cost of packed cell and platelet transfusions were RM561.37 and RM238.12, respectively. Mean medication cost was RM15,160, RM98,525 and RM97,229 respectively from 1st to 3rd-4th lines of therapy.

Conclusion: Preliminary analysis indicates that for MF treatment costs in Sarawak MOH hospitals, cost of hospitalisation incurs greater cost than transfusion and outpatient visits, while for medication, the cost of first line medication was the lowest. This registry provides a real-world overview of MF patients in our state and highlights key insight into the unmet clinical need.


Ab

stract - C

linica

l Resea

rch

Ab

stract - C

linica

l Resea

rch

C21

EPIDEMIOLOGY AND CLINICAL PROFILES OF CUTANEOUS GRAFT VERSUS HOST DISEASE IN ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION

Nor Saaidah Kamal Rodin1, Nor Azimah Ismail1, S. Fadilah Abdul Wahid1, Adawiyah Jamil2, Syed Zulkifli Syed Zakaria3, Sharifah Shahnaz Syed Abd Kadir4, Lee Bang Rom5, Ikmal Hisyam Bakrin6, Wan Fariza Wan Jamaludin1

1 Pusat Terapi Sel, Hospital Canselor Tuanku Muhriz, Cheras, Kuala Lumpur, Malaysia; 2 Department of Medicine, Hospital Canselor Tuanku Muhriz, Cheras, Kuala Lumpur, Malaysia; 3 Department of Pediatric & Community Health, Hospital Canselor Tuanku Muhriz, Cheras, Kuala Lumpur, Malaysia; 4 Department of Haematology, Hospital Ampang, Ampang, Selangor, Malaysia, 5 Department of Dermatopathology, Hospital Gleneagles, Kuala Lumpur, Malaysia, 6 Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia

[email protected]

Background: The epidemiology and clinical profiles of cutaneous graft versus host disease (GVHD) in allogeneic peripheral blood stem cell transplantation (PBSCT) in Malaysia has not been well described.

Objectives: The objective of this study is to investigate the prevalence, clinical profiles, severity, treatment outcomes and survival rates of cutaneous GVHD in allogeneic peripheral blood stem cell transplantation.

Materials and Methods: A retrospective study was conducted in Hospital Canselor Tuanku Muhriz and Hospital Ampang from January 2010 to December 2017 (8 years) involving 691 allogeneic PBSCT patients.

Results: The prevalence of cutaneous GVHD was 31.4% (217/691). No associations were detected with race, age or gender of donor and recipients. Cutaneous GVHD was associated with host cytomegalovirus (CMV) seropositivity (p<0.01), conditioning (p<0.01), GVHD prophylaxis (p=0.046) and survival (p<0.01). Majority developed the acute form (58.1%;126/217). Biopsies in 20.7% (45/217) showed 55.6% positivity for GVHD. Overall, involvement was non-severe. A majority demonstrated complete response (CR) to first-line corticosteroids (70.0%;152/217). Second line therapies (extracorporeal phototherapy (ECP), psoralen ultraviolet A (PUVA), mycophenolate, tumour necrosis factor (TNF) inhibitors, interleukins inhibitors, or CD20 monoclonal antibodies) were required in 65/217, with 38.5% CR. Second-line therapy was associated with gender (p=0.042), extra-cutaneous GVHD (p=0.021), treatment outcomes (p=0.026) and survival (p=0.048). Mortality in cutaneous GVHD was 24.0% with severe sepsis being the leading cause at Day 100 (7.8%) and 5-years (7.8%), and relapsed disease at 2-years (32.7%). In steroid refractoriness, severe GVHD caused 30.8% mortality. In cutaneous GVHD, survival at Day 100 was 95.4%; 80.2% at 2-years and 73.1% at 5-years. The median survival in cutaneous GVHD was significantly shorter at 55 months, compared to those without GVHD at 69 months (p=0.001).

Discussion: The prevalence of cutaneous GVHD was 31.4%, slightly lower compared to published data at 40%. Cutaneous GVHD was diagnosed clinically and an invasive skin biopsy was not mandatory unless in clinical uncertainty or in steroid-refractory GVHD. CMV seropositivity, conditioning regimens, and GVHD prophylaxis were significantly associated with cutaneous GVHD in agreement with previous reports. Corticosteroids are established as the standard frontline therapy for acute GVHD. Steroid refractoriness was observed in 30% of patients, and was slightly lower than 35-60% reported previously. We observed 38.5% CR and 53.8% improvement to second line therapy, compared to 29.7% for acute GVHD and 44.4% for chronic GVHD as reported previously. GVHD and steroid refractoriness was associated with shorter survival and increased Transplant Related Mortality.

Conclusion: Cutaneous involvement is the commonest clinical manifestation of GVHD. A larger national study is warranted to further analyse severity and outcome of multiorgan GVHD, and factors associated with steroid refractoriness.


Ab

stract - C

linica

l Resea

rch

C21 C22

FEASIBILITY AND SAFETY OF COLLECTION OF MONONUCLEAR CELLS FOR AUTOLOGOUS CHIMERIC ANTIGEN RECEPTOR-T (CAR-T) CELL THERAPY IN HAEMATOLOGIC MALIGNANCIES

Wint Wint Thu Nyunt1, Timothy Lim1, Mohd Razif Mohd Idris2, S Fadilah S Abdul Wahid2

1 Plutonet Sdn. Bhd, Selangor, Malaysia; 2 Pusat Terapi Sel (PTS), Faculty of Medicine, Hospital Canselor Tuanku Muhriz Universiti Kebangsaan Malaysia (HCTM UKM), Kuala Lumpur, Malaysia

[email protected]

Background: The first step in manufacturing for autologous Chimeric Antigen Receptor-T (CAR-T) cell therapy is to collect autologous CD3+ T lymphocytes by leukapheresis. Patient factor (leucopenia due to haematologic malignancy or multiple lines of chemotherapy) leads to challenges in obtaining adequate yield of autologous CD3+ T cells via collection of mononuclear cells (MNC) by leukapheresis.

Objective of this study is to evaluate the feasibility and safety of collecting adequate numbers of autologous MNC and risk factors for inadequate collection.

Materials and Methods: In this prospective study, patients with relapsed/ refractory B-acute lymphoblastic leukaemia (r/r B-ALL) or relapsed/ refractory B-non-Hodgkin’s lymphoma (r/r B-NHL) who were referred for enrolment into autologous CD19-directed CAR-T clinical trials at PTS, HCTM UKM were screened. Among them, 22 patients underwent leukapheresis, for collection of MNC aiming for production of CAR-T product, within 3-year-period (2019 to July 2022). Data were collected. Data analysis was performed by using SPSS version 23.0. According to the local manufacturer’s recommendation, successful collection of MNC is defined as achievement of target cell dose of at least 2x10^9 cells during leukapheresis; and the minimum number of CD3+ lymphocytes from patients’ leukapheresis product to be accepted for CAR-T manufacturing is 150 x10^6 cells.

Results: Data of 22 patients (11 r/r B-ALL; 11 r/r B-NHL) were analysed. All the patients had single leukapheresis. The median age at leukapheresis was 32 (range: 18-74) years. Among r/r B-ALL patients, 4 (36.4%) had allogeneic haematopoietic cell transplantation (HCT) and 1 (9.1%) had autologous-HCT. Among r/r B-NHL patients, 6 (54.5%) had autologous-HCT. Among r/r B-ALL, 4 (36.4%) had 2 lines, 6 (54.5%) had 3-4 lines and 1 (9.1%) had >5 lines of therapy prior to leukapheresis. Among r/r B-NHL, 1 (9.1%) had 2 lines, 6 (54.5%) had 3-4 lines and 4 (36.4%) had ≥5 lines of therapy prior to leukapheresis. The medium number of peripheral blood (PB) lymphocyte count on the same day prior to leukapheresis was 1.1 x10^9/L (range: 0.3-289.6 x10^9/L). The median numbers of total nucleated cells (TNC) collected, MNC and CD3+ cells in isolated MNC were 5.3 x10^9 cells (range: 0.7-11.8 x10^9), 4.3 x10^9 cells (range: 0.7-11.8 x10^9) and 2290 x10^6 cells (range: 21.1-8523 x10^6), respectively. Viability of TNC ranged from 91.4-100%. The rate of successful collection of autologous MNC was 95.5% (n=21). Only one patient (r/r B-ALL) (4.5%) did not achieve the target yield of MNC. Only one patient (4.5%) suffered from tingling sensation (hypocalcaemia) which was fully recovered whereas 95.5% (n=21) underwent the uneventful procedure.

Discussion & Conclusion: Leukapheresis for collecting adequate numbers of MNC was feasible and safe in most patients planned for CAR-T cell therapy. Risk factors for inadequate collection of MNC or CD3+ cells were low PB lymphocyte count, high PB reticulocyte count and high percentage of PB blasts. Factors which showed positive correlation with the number of MNC were PB white cell count, PB lymphocyte or monocyte count (on the same day prior to leukapheresis). Determination of these factors prior to leukapheresis can help in deciding the right timing for collection of MNC. Patient selection and timing play crucial roles in ensuring successful collection of autologous MNC for CAR-T cell therapy in r/r B-ALL and r/r B-NHL. Limitation of this study was small sample size; and the updated analysis will be presented upon completion of the clinical trials.


Ab

stract - C

linica

l Resea

rch

Ab

stract - C

linica

l Resea

rch

C23

LONG-TERM CLINICAL OUTCOMES OF AUTOLOGOUS BONE MARROW MONONUCLEAR CELL IMPLANTATION IN PATIENTS WITH SEVERE THROMBOANGIITIS OBLITERANS

Farina Mohamad Yusoff1, Masato Kajikawa2, Yuji Takaeko3, Shinji Kishimoto1, Haruki Hashimoto3, Tatsuya Maruhashi1, Yasuki Kihara 3, Ayumu Nakashima4 & Yukihito Higashi1,2

1Department of Regenerative Medicine, Division of Radiation Medical Science, Research Institute for Radiation Biology and Medicine (RIRBM), Hiroshima University, Japan. 2Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan. 3Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan. 4Department of Stem Cell Biology and Medicine, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.

[email protected]

Background: Patients with severe Buerger disease, also known as thromboangiitis obliterans (TAO), are at risk of major limb amputation. It has been shown that autologous bone marrow mononuclear cell (BM-MNC) implantation improves the condition of critical limb ischemia in TAO patients. This study was conducted to further clarify the long-term (>10 years) results of autologous BM-MNC implantation in patients with severe TAO.

Materials & Methods: This study was a retrospective observational study to determine the long-term outcomes of BM-MNC implantation in 47 lower limbs of 27 patients and 22 lower limbs of 18 control patients with TAO. Amputation-free survival rates were compared between TAO patients and both the internal controls and historical controls. To identify limb survival projections as an internal control, the same limbs that were diagnosed with severe TAO and had no option for conventional treatments were estimated for amputation at the time of BM-MNC implantations were performed. Additional data for the patients was obtained to determine overall survival and major amputation-free survival rates. We also report causes of death in patients after more than 10 years of follow-up.

Results: The mean follow-up period was 12.0±8.6 years. There was no major amputation event up to 10 years of follow-up in patients treated with BM-MNC implantation. The overall amputation-free survival rates were significantly higher in patients who underwent BM-MNC implantation than in internal controls and historical controls. There was no significant difference in amputation-free survival rates between the historical and internal controls. There was also no significant difference in overall survival between patients who underwent BM-MNC implantation and the historical controls.

Discussion & Conclusion: BM-MNC transplantation successfully prevented major limb amputation over a period of >10 years in patients with severe TAO who had no other therapeutic options.


Ab

stract - C

linica

l Resea

rch

C24

PERSISTENCE AND DECAY OF ANTI-SARS-COV2 IG G ANTIBODY RESPONSE POST BNT162B2 SARS-COV-2 ( PFIZER-BIONTECH, COMIRNATY) VACCINE IN PATIENT WITH VARIOUS HAEMATOLOGICAL CONDITIONS

Pei Ling Low 1 ,Tanusha Kunju 2 ,Veena A/P Selvaratnam3

Ampang Hospital, Ampang, Selangor, Malaysia

[email protected]

Background: Patients with hematologic malignancies are at high risk for coronavirus disease 2019 (COVID-19)-related complications, with mortality rates exceeding 30%. In most haematological patients, a compromised immune system due to the disease per se, the treatment, or a combination of both, might be responsible for an increased risk for severe or even life-threatening COVID-19. The main objective of this systematic review was to assess the immunogenicity of COVID- 19 vaccines in patients with various hematologic conditions.

Materials and Methods: We conducted a retrospective analysis in adult patients with various haematological diseases who received two doses BNT162b2 (Biontech/Pfizer) Humoral immunity response will be assessed in these patients, via determining the antibody rise post vaccination and different intervals over a period of 6 months. For each patient, antibody level will be taken on the following interval, pre 1st dose vaccination, pre 2nd dose vaccination, 2 weeks post 2nd dose vaccination , 3 months and 6 months after completed 2 doses vaccination. The antibodies a measures using the Elecsys Anti-SARS-CoV-2 immunoassay serology test run on an automated platform; Roche’s Cobas e platform. These results are expressed as extinction coefficient (signal/cutoff) ratios and are interpreted as positive ( 1.00), equivocal (> 0.80 to < 1.00), or non-reactive ( 0.80). We would like to divide our patients to malignant and non malignant category and determine if there is any difference in response. The non malignant population will include patients with underlying haemophilia who are immunocompetent and therefore expected to have predictably good response.

Results: In total, we analyzed n 148 patients, of these n=9 patiens suffered from premalignant disorder, n= 91 patients suffered from haematological malignancy, n=48 patients suffered from benign haematological disorders. Patients in benign haematological disorder cohort will be further subcategorized as immunosuppressed versus immunocompetent. We are putting patient with haematological malignancy as immunosuppressed arm. As treatment status has been found to be a relevant predictor for serological response rate to SARS-CoV2vaccination. we further subdivided the disease cohorts into the following categories: on therapy, off treatment more than 6 months, post-allosct, post autosct. We noticed n=6 unable mount adequate antibody response even after 2 doses vaccine. Of these, n=2 patients are receiving chemotherapy, n=2 received chemotherapy less than 6 months ago, n=2 known case of hypogammaglobulinemia. N=9 patieent contracted covid even though antibody level still detected in relatively high level, n=7 infected covid within 6 months of vaccination, n=2 after 6 months vaccination. N=103 patients in immunosuppressant arm, n=97 patient able to mount adequate antibody as immunocompetent patient.

Conclusion: Majority of immunocompromised patient able to mount and sustained antibody response as immunocompetent patient. Majority of patient has antibody detected up to 6 months. Patient with certain condition such as hypogammaglobulinemia respond to vaccine poorly.


Ab

stract - C

linica

l Resea

rch

Ab

stract - C

linica

l Resea

rch

C25

PREVALENCE AND SPECIFICITY OF RBC ALLOIMMUNIZATION AMONG CHRONIC LIVER DISEASE PATIENT IN HOSPTAL UNIVERSITI SAINS MALAYSIA

Siti Zaleha S Abdullah1, Mohd Nazri Hassan1, Marini Ramli1

1 Department of Hematology and Transfusion Medicine Unit, School of Medical Science, Health Campus, University Science Malaysia 16150 Kubang Kerian, Kelantan, Malaysia

[email protected]

Background: Red blood cells (RBCs) alloimmunization is a common condition especially in patient who receive multiple transfusions, such as patients with thalassemia and hematological malignancies. It has a potentially serious effect on blood transfusions as extensive matching of donor need to be provided. Variations in the frequency of alloimmunization have been noted among different patient population. Patient with underlying liver disease had an overall statistically significant impact on the rate of alloimmunization.Objective: To determine the prevalence and specificity of RBCs alloantibodies among chronic liver disease (CLD) patients in our centre.

Materials and Methods: Four hundred and seventy-five (475) patients diagnosed as CLD were identified from medical unit record from 1st April 2012 until 30th April 2022. This ten years retrospective study was conducted by collecting the clinical and laboratory data extracted from blood bank information system and patient’s medical record.

Results: The mean age of the patients was 58 years old. Most were Malays (92%) and male (64.2%). The commonest aetiology of CLD was Hepatitis B (39.9%), followed by Hepatitis C (23.9%), cryptogenic (21.7%) and NAFLD (11.2%). A total of 27 CLD patients were reported to have RBC alloantibodies which resulting overall prevalence of 5.7%. Most alloimmunized patients had a single alloantibody (85.2%). The alloimmunization rate was slightly higher in in females (8.8%) than males (4.1%). Higher rates of alloimmunization were seen in patients with chronic Hepatitis C (33.3%) and Hepatitis B (18.5%) infection. The most common alloantibody was anti-E (40.7%), followed by anti-Mia (18.5%) and anti-c (14.8%).

Discussion: The prevalence of alloimmunization among CLD patients in this study were similar to other studies ranging from 5.2% to 23%. Anti-E was found to be the most commonly implicated antibodies and similar results were observed in other studies among Asian population. Higher rates of alloimmunization among Hepatitis C and Hepatitis B patient possibly due viral-type inflammation that leads to enhanced antigen specific immunity as suggested by other study. A large-scale prospective study at specific post transfusion time interval should be done in the future to accurately determine the rate of alloimmunization in CLD patient.

Conclusion: This study highlights that underlying CLD may be an important factor in determining a patient’s susceptibility to alloimmunization. RBC phenotyping should be performed on patients who are at high risk of alloimmunization and are likely to require multiple transfusions, and they should be given phenotype-matched blood.


Ab

stract - C

linica

l Resea

rch

C26

REAL WORLD OUTCOME OF CHRONIC LYMPHOCYTIC LEUKAEMIA PATIENTS TREATED WITH VENETOCLAX IN HOSPITAL AMPANG, SELANGOR

Jerome Tan Tsen Chuen1, Ho Kim Wah1, Chow Lai Chee1, Christopher Ng1, Ganesh Kasinathan1, Sharifah Shahnaz Alkudsi1, Tan Sen Mui1

1Department of Haematology, Hospital Ampang Selangor

[email protected]

Background: Chronic Lymphocytic Leukaemia (CLL) is a chronic lymphoproliferative disorder which mainly affects the elderly. These patients usually have multiple co-morbidities and are unfit for intensive chemoimmunotherapy. Historically, therapeutic options are limited to alkylating agents and later on anti CD20 monoclonal antibodies such as Rituximab and Obinutuzumab. Purine analogues such Fludarabine are usually reserved for younger fit patients. Thus, many newer targeted novel therapies have been developed to address this medical need. Venetoclax, a novel targeted agent which blocks the anti-apoptotic BCL-2 protein leading to programmed cell death is a promising therapy in the treatment of CLL which has been FDA approved since 2016.

Objectives: To look at the real-world outcome of CLL patients treated with Venetoclax between 2020-2022 in Hospital Ampang, Selangor.

Methods and Materials: This is a retrospective analysis of 6 patients who had received Venetoclax as part of their CLL therapy. The demographics, disease characteristic, prior treatment status and outcome of these patients were analyzed.

Results: The CLL patients were diagnosed between year 2002-2021. All 6 patients were males and the median age at diagnosis was 61 years (48-72). 33.3% (2) of patients were treatment naive while 66.7% (4) were relapse or refractory cases with prior therapies. Prior therapies received were Chlorambucil-prednisolone, R-CVP, R-CHOP or R-Fludarabine. Prior to commencing Venetoclax therapy, 2 patients had Del17p, 2 had trisomy 12, 1 had Del13q and 1 had no genetic abnormality via FISH testing. Venetoclax was combined with Rituximab in 2 patients, with Obinutuzumab in 2 patients and as monotherapy maintenance in 2 patients after initial “induction” chemoimmunotherapy. One patient had BR x3 “induction” while the other had R-CHOP x6 for a localized Richter’s transformation of a lymph node. All patients achieved a complete haematological response. At data cut-off date or death, with a median follow up of 59 weeks (26-129), the overall survival was 66.7% (4). The mean duration of Venetoclax therapy was 58 weeks with a median of 59 weeks (26-102). No patient had progressed or relapsed. However, bone marrow assessment for MRD was not performed as this is not done routinely in our clinical practice. Unfortunately, 2 deaths had occurred due to Covid-19 infection, at week 29 and 102 respectively. Interestingly both patients were fully vaccinated and had received the combination of Obinutuzumab with Venetoclax.

Discussion: Venetoclax appears to be efficacious even in heavily pre-treated patients who had received conventional alkylating agents or chemoimmunotherapy. Patients with or without poor risk chromosomal abnormalities responded to treatment. All patients improved clinically with normalization of haematological parameters and general well-being. It would be desirable to have genomic and MRD data to assess the depth of response.

Conclusion: This early data appears promising for CLL patients in a real-world setting. However, the numbers here are small and follow up period is short. More therapeutic options are now available to patients but access to novel targeted agents such as Venetoclax remains challenging.


Ab

stract - C

linica

l Resea

rch

Ab

stract - C

linica

l Resea

rch

C27

RED BLOOD CELL ALLOIMMUNIZATION AND AUTOIMMUNIZATION IN TRANSFUSION DEPENDENT THALASSEMIA: A SINGLE CENTRE RETROSPECTIVE REVIEW

Kee Tat Lee1, Khairulnisa A Manap2, Mohd Haffis Mohd Nor2, Sui Keat Tan3, Ai Sim Goh3

1Medical Department, Hospital Seberang Jaya, Pulau Pinang, Malaysia; 2Transfusion Medicine Unit, Pathology Department, Hospital Seberang Jaya, Pulau Pinang, Malaysia; 3Hematology Unit, Medical Department, Hospital Pulau Pinang, Malaysia

Kee Tat Lee ([email protected])

Background: Development of alloantibodies and autoantibodies against red blood cell (RBC) antigens remains a major problem in thalassemia patients. These antibodies complicate transfusion therapy and lead to increase need for blood transfusion and its complications. The aim of this study is to evaluate the frequency of red cell alloimmunization and autoimmunization in our adult transfusion dependent thalassemia (TDT) and analyze the factors that possibly affect antibody formation.

Materials and Methods: A retrospective review of all adult TDT who received treatment in Hospital Seberang Jaya, Pulau Pinang was conducted. Clinical and transfusion records were analyzed. Demographic data, types of thalassemia, age of initiation of transfusion therapy and status of splenectomy were reviewed. Data were analyzed using Statistical Package for Social Sciences software (version 21.0).

Results: A total of 54 adult TDT patients (29 males and 25 females) were included in this study. The age of patients ranged from 18 to 52 years with a mean age of 24.9 years. Majority of TDT in our centre were Malay (90.7%) and followed by Chinese (7.4%) and Indian (1.9%). Among the TDT, HbE-Beta thalassemia (57.4%) are most common, followed by beta thalassemia major (38.9%) and non-deletional HbH (3.7%). The frequency of RBC alloantibodies was 31.5% (17/54) and autoantibodies was 7.4% (4/54). Of the 17 patients that were positive for alloantibodies, 64.7 % had single alloantibody and 35.3% had at least two or more of alloantibodies. A total of 26 alloantibodies were identified and majority were directed against Rh and MNS antigen. Anti-E (38.6%) was the most frequent, followed by anti-c (15.5%), anti-S (11.5%) and Anti-Mia (11.5%). All the four patients with autoantibodies were positive for alloantibodies. Eight patients (14.8%) had been splenectomized. However, the alloimmunization incidence was not influenced by age of initiation of transfusion, ABO blood group and splenectomy. Alloimmunization had a significant relationship with gender of patient (p=0.004).

Discussion & Conclusion: Our study demonstrated that antibodies against the Rh and MNS were more frequent among the adult TDT in our centre. The high incidence of alloimmunization in the study population re-emphasizes the importance of RBC antigen typing before first transfusion. We would like to recommend issue of antigen matched blood for Rh and MNS antigen to reduce risk of alloimmunization and improve the efficiency of blood transfusion. Further evaluation with larger sample size should be conducted to look into common alloantibodies in our population.


Ab

stract - C

linica

l Resea

rch

C28

RELATIONSHIP BETWEEN CELL NUMBER AND CLINICAL OUTCOMES OF AUTOLOGOUS BONE‐MARROW MONONUCLEAR CELL IMPLANTATION IN CRITICAL LIMB ISCHEMIA

Farina Mohamad Yusoff1, Masato Kajikawa2, Yuji Takaeko3, Shinji Kishimoto1, Haruki Hashimoto3, Tatsuya Maruhashi1, Ayumu Nakashima4, S. Fadilah S. Abdul Wahid5 & Yukihito Higashi1,2

1Department of Regenerative Medicine, Division of Radiation Medical Science, Research Institute for Radiation Biology and Medicine (RIRBM), Hiroshima University, Japan. 2Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan. 3Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan. 4Department of Stem Cell Biology and Medicine, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan. 5Pusat Terapi Sel (Cell Therapy Centre), Universiti Kebangsaan Malaysia (UKM) Medical Centre, Kuala Lumpur, Malaysia.

[email protected]

Background: Cell therapy using intramuscular injections of autologous bone-marrow mononuclear cells (BM-MNCs) improves clinical symptoms and can prevent limb amputation in atherosclerotic peripheral arterial disease (PAD) patients with critical limb ischemia (CLI). The purpose of this study was to evaluate the effects of the number of implanted BM-MNCs on clinical outcomes in atherosclerotic PAD patients with CLI who underwent cell therapy.

Materials & Methods: This study was a retrospective observational study. BM-MNC implantation compared to those in internal controls and historical controls. To identify limb survival projections as an internal control, the same limbs as those that were diagnosed with CLI and had no option for conventional treatments were estimated for amputation at the time when BM-MNC implantations were performed. Additional data for the relationships of implanted cell number with updated overall survival, major amputation-free survival rates, and MACE in atherosclerotic PAD patients with CLI who underwent BM-MNC implantation were evaluated.

Results: The median follow-up period of 13.5 years (range, 6.8–15.5 years) from BM-MNC implantation procedure. The mean number of implanted cells was 1.2 ± 0.7 × 109 per limb. There was no significant difference in number of BM-MNCs implanted between the no major amputation group and major amputation group (1.1 ± 0.7 × 109 vs. 1.5 ± 0.8 × 109 per limb, P = 0.138). There was also no significant difference in number of BM-MNCs implanted between the no death group and death group (1.5 ± 0.9 × 109 vs. 1.8 ± 0.8 × 109 per patient, P = 0.404).

Discussion & Conclusion: Differences in the number of BM-MNCs (mean number, 1.2 ± 0.7 × 109 per limb) for cell therapy did not alter the major amputation-free survival rate or mortality rate in atherosclerotic PAD patients with CLI. A large number of BM-MNCs will not improve limb salvage outcome or mortality.


Ab

stract - C

linica

l Resea

rch

Ab

stract - C

linica

l Resea

rch

C29

THE DISTRIBUTION OF BCR-ABL1 FUSION TRANSCRIPTS AND THE INCIDENCE OF BLASTIC TRANSFORMATION AMONG CML PATIENTS IN KELANTAN

Nabihah M Shakri¹, Marini Ramli¹, M Nazri Hassan¹, Sinari Salleh², Aini Syakirah A Shuyuti²

¹Department of Haematology Universiti Sains Malaysia, Kelantan, Malaysia; ²Department of Medicine, Hospital Raja Perempuan Zainab II, Kelantan, Malaysia Malaysia.

[email protected]

Background: Chronic myeloid leukemia, BCR-ABL1-positive is characterized by the presence of the Philadelphia chromosome, while at the molecular level a fusion of part of the ABL and BCR genes is observed. Breakpoints in the BCR gene can be variable. In majority of cases, the breakpoints almost always occur in the major breakpoint cluster region (M-BCR). The resulting fusion transcripts are named e13a2(b2a2) and e14a2(b3a2) which encode for a p210 BCR-ABL1 proteins. These fusion transcripts may influence the phenotype of the disease. In terms of its clinical course, most of the CML patients are diagnosed in chronic phase and without effective therapy, progression into accelerated or blastic phase can happen. Objective of this study is to determine the distribution of BCR-ABL1 fusion transcripts among CML patients in Kelantan and the incidence of blastic transformation among them.

Materials and Methods: Ninety-six (96) patients diagnosed as CML identified from Hematology record in HUSM and HRPZII from January 2010 until December 2021 were recruited. This is a 12-year retrospective study conducted by collecting clinical and laboratory data from patient’s medical record from record office Hospital USM and Klinik Pakar Perubatan HRPZII. All CML patients aged ≥ 18 years old with positive molecular results were included in the study while CML patients aged <18 years old and incomplete data were excluded.

Results: Data of 96 CML patients were analyzed. The mean age was 40 years old. Most were Malays (91%) and males (74%). 56 (58.3%) had the e14a2 type BCR-ABL1 transcripts and 40 (41.6%) had e13a2 type with ratio of 1.4:1. 14 cases had blastic transformation of CML. There were 9 cases (64.2%) and 5 cases (28.6%) involving the e13a2 and e14a2 type BCR-ABL1 transcripts respectively. Out of 14 cases, 9 cases (64.2%) transformed into myeloid blast crisis, 4 (28.6%) B-lymphoid blast crisis and 1 (7.1%) B/myeloid blast crisis.

Discussion & Conclusion: The incidence of different types of BCR-ABL1 fusion transcripts among CML patients had been outlined in several studies around the world. Most of the previous studies had reported higher frequency of e14a2 transcripts in their CML patients. Contrasting data were recorded in 3 other studies where e13a2 transcripts were dominant. Few studies documented a small number of patients with co-expression of e13a2+e14a2 transcripts which were not seen in our population. In conclusion, our study showed that majority of CML patients in Kelantan had the e14a2 type BCR-ABL1 fusion transcript. Whilst e13a2 type showed higher incidence of blastic transformation which is as suggested by other study as well. Therefore, the identification of which subtype of fusion transcripts at diagnosis is important as it may help in better prognostication of the disease in predicting disease transformation.


Ab

stract - C

linica

l Resea

rch

C30

TREATMENT FREE REMISSION (TFR) IN CHRONIC MYELOID LEUKEMIA (CML) -A MALAYSIAN PRIVATE CENTER EXPERIENCE.

Soo-Chin Ng , Alan Teh and TZ lim

Subang Jaya Medical Center

[email protected]

Background: The current goal in treatment of CML in recent years is to attain normal life span with good quality of life and the opportunity to go off treatment i.e., treatment free remission (TFR). Though TKI (tyrosine kinase inhibitor) has outstanding results in treating CML with overall survival rates of 85–90% at 10 years, the long-term usage of TKI has associated problems which include side effects such as peripheral edema, gastrointestinal upsets, pleural effusion (dasatinib) and vascular complications (ponatinib); not forgetting the financial toxicity to patient and the society plus impact on real life events such as pregnancy.

Objectives: This study documents our pilot study result of TFR at SJMC.

Materials and Methods: The records of 13 patients on the TFR program are reviewed. Only patients who had attained Deep Molecular Remission (DMR) MR 4.5 (BCR-ABL1IS <0.0032%) that lasted for at least 2 years were enrolled. In this study, all the patients have 5 years of TKI therapy before stopping TKI. They are monitored monthly with inhouse BCR ABL quantitative test for first 6 months followed by 2 monthly molecular test for next 6 months Thereafter they need 3 monthly molecular tests indefinitely. MR (molecular relapse) was defined as the loss of the MMR (BCR-ABL1IS >0.1%.

Results: Thirteen patients (10 males and 3 females) with age ranging from 34-78 years (median age 56) participated in the study. Seven patients were on nilotinib while 6 patients were on imatinib. Mean duration of sustained DMR before starting TFR was 4.3 years (Range 3 years - 9 years 2 months).

Only one out of 13 patients complained of TKI withdrawal symptoms ice , small peripheral joint swelling and pain needing analgesics for first 4 weeks .Three patients complained of mild symptoms and did not need any medications.

Five out of the 13 (38.5%) patients had molecular relapse which happened all within 6 months (2,3,3,5 months respectively) except for one patient which occurred 4 years 1 month later. Four patients were restarted on TKI attained DMR again. The late relapse patient is being monitored as he had fluctuating level of BCR ABL transcript reading bordering 0.1 % for the past 2 years. The mean of period of TFR was 23 months (range :3 months to 5 years 9 months). Two out of six (33.3%) patients with low sokol’s score relapsed while 2 out of 5 (40%) of intermediate and 1 out of 2 (50%) of high-risk group relapsed.

Discussion: This study showed the feasibility of introducing TFR in our local patients. The results were satisfactory as eight of 13 (61.5%) are enjoying TFR which return them to normal life. The withdrawal symptoms are manageable and patients who relapsed can be salvaged with the same TKI.

Conclusions: TFR should be discussed with new CML patients to motivate them to be complaint with TKI therapy to maximise the chance of deep molecular remission. This will enable them to participate in the TFR program which is highly beneficial to them.


Ab

stract - C

linica

l Resea

rch

Ab

stract - C

linica

l Resea

rch

C31

UTILISATION OF THERAPEUTIC PLASMA EXCHANGE IN TREATING TRANSPLANT-ASSOCIATED THROMBOTIC MICROANGIOPATHY: A SINGLE CENTRE RETROSPECTIVE CROSS-SECTIONAL COHORT STUDY

Wong YS1, Sharifah Shahnaz SAK1, Ho KW1, Ong TC1, Tan SM1

1Department of Haematology, Ampang Hospital, Selangor, Malaysia.

[email protected]

Background: Transplant-associated thrombotic microangiopathy (TA-TMA) is an established complication of allogeneic haematopoietic stem cell transplantation (HSCT) that results in significant morbidity and mortality. Despite it being a recognised post-transplant sequelae, there are no well-defined treatment algorithms to guide the management of this condition. The objectives of this study are to identify the clinical outcomes of allogeneic HSCT patients who have undergone therapeutic plasma exchange (TPE) for the treatment of TA-TMA, and to determine certain therapy related factors such as the median duration of treatment with TPE.

Materials and Methods: The electronic medical records of all patients with TA-TMA in Ampang Hospital diagnosed over a 5 year period (January 2017 to December 2021) were reviewed. Collected data consisted of patients’ demographics, clinical characteristics, therapeutic interventions and clinical outcomes.

Results: In this cohort, a total of 25 patients with TA-TMA were identified within the determined time frame. All patients diagnosed with TA-TMA were treated with TPE, alongside more well established management strategies such as the withdrawal of calcineurin inhibitors (CNIs). The median number of cycles of TPE administered is 6 cycles (range, 1 to 56 cycles). 19 of the 25 patients in this cohort eventually died, with TA-TMA being the direct cause of death for 13 of those cases.

Discussion and Conclusion: There is a paucity of data regarding the use of TPE in the treatment of patients with TA-TMA, particularly amongst adult patients. This study sheds some light on the value of early initiation of TPE in this population of patients, and provides optimism that TPE represents a viable and useful treatment option in resource-limited settings with restricted access to novel therapeutic agents.


Ab

stract - C

linica

l Resea

rch

C32

VASOVAGAL REACTION AMONG BLOOD DONORS: PREVALENCE AND FACTOR ASSOCIATED

Nur Nasuha Ibrahim¹·², Noor Haslina Mohd Noor¹·²,Zefarina Zulkafli¹·²

1Department of Hematology and Transfusion Medicine Unit, School of Medical Science, Health Campus, University Science Malaysia 16150 Kubang Kerian, Kelantan, Malaysia ; 2 Hospital Universiti Sains Malaysia, 16150, Kubang Kerian, Kelantan, Malaysia.

[email protected]

Background: Adverse events during donation process especially vasovagal reactions has the most negative impact on the blood donor return rate.

Objective: Objective of this study is to determine the prevalence of vasovagal reaction among blood donor and to study the associated biological factors among vasovagal donors at Hospital Universiti Sains Malaysia (HUSM) Malaysia.

Material & Methods: This three years retrospective study was conducted by using the data that were extracted from blood bank databases system and from Incident of Adverse Reaction form which was registered from 1st June 2018 until 30th June 2021. A hundred and fifty-nine (159) blood donor who developed adverse donor reaction will be selected as a case sample and by using a ratio of 1:2, three hundreds and eighteen (318) non vasovagal donor were selected randomly. The biological and donor factors of all sample were analysed including age, gender, race, weight, volume of blood collected, donation status and donation site.

Results. A total of 159 donors were reported to have vasovagal reactions which resulting overall prevalence of 0.45%. Dizziness or mild vasovagal reactions were the most frequently observed adverse reactions, accounting for approximately 87/159 (54.7%) of all adverse reactions. Factors that were significantly associated with vasovagal reactions were female, weight more than 55kg, first time donor and volume of blood collected is 450ml.

Discussion: The prevalence of vasovagal reaction among blood donor in this study it was low which was similar to few previous studies. Although the number of donors who developed adverse reactions during or immediately after the blood donation was very low, still it is very important to reduce risks to a minimum so that donor return rate could be maintained.

Conclusion: The factors associated will help to identify high risk donor to prevent the incidence. Careful selection and evaluation of blood donors by experienced physicians or trained nurses play an important role in prevention of adverse reactions.


Ab

stract - La

bo

rato

ry Resea

rch

Ab

stract - La

bo

rato

ry Resea

rch

ASSOCIATION OF MANNOSE-BINDING LECTIN (MBL) GENE POLYMORPHISMS WITH IMMUNE THROMBOCYTOPENIA IN KELANTAN, MALAYSIA

Muhamad Aidil Zahidin1, Noor Haslina Mohd Noor1,2*, Muhammad Farid Johan1, Abu Dzarr Abdullah3, Zefarina Zulkafli1,2, Hisham Atan Edinur4

1Department of Haematology, School of Medical Sciences, Universiti Sains Malaysia (Health Campus), 16150 Kubang Kerian, Kelantan Malaysia; 2Transfusion Medicine Unit, Hospital Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan Malaysia. 3Department of Medicine, School of Medical Sciences, Universiti Sains Malaysia (Health Campus), 16150 Kubang Kerian, Kelantan Malaysia; 4Forensic Science Programme, School of Health Sciences, Universiti Sains Malaysia (Health Campus), 16150 Kubang Kerian, Kelantan Malaysia.

[email protected]

Background: The mannose-binding lectin (MBL) is a protein that plays an essential role in the innate immune response. Human immunodeficiencies caused by MBL deficiency have associated gene variations with a range of diseases. Immune thrombocytopenia (ITP) is an autoimmune disorder characterised by isolated thrombocytopenia. The immune system reacts with a platelet antigen, resulting in thrombocytopenia. To our knowledge, studies on the association of MBL and ITP have not been widely conducted. Analysis of polymorphisms in MBL genes is important for understanding the pathophysiology of ITP. Thus, we investigated associations between polymorphisms in MBL genes and ITP patients in Kelantan.

Materials & Methods: The participants in this study comprised 30 patients with ITP and 30 unrelated healthy controls. All participants were informed, and a basic demographic background was recorded. Approximately 10 cc of blood was taken and stored in the EDTA tube. The genomic DNAs were isolated from peripheral blood and MBL gene polymorphisms (-550nt, rs11003125, *H/*L; -221nt, rs7096206, *X/*Y; +4, rs7095891, *P/*Q; +223nt, rs5030737, *A/*D; +230nt, rs1800450, *A/*B; and +239nt, rs1800451, *A/*C) were subjected to polymerase chain reaction (PCR) and sequenced based on existing protocols. The distribution of haplotype, genotype, and allelic was directly counted from the raw sequences. Analyses for the studied polymorphisms were conducted using chi-square test. Odd ratios (OR) with 95% confidence intervals (CI) were calculated using IBM SPSS Statistics v28.0.1.

Results: We identified six haplotypes in a Kelantan population, which are HYPA, HXPA, LXPA, LXPB, HYPB, and LYPB. Haplotype HYPA (35.00%) and LYPB (5.00%) are the most and least dominant haplotypes, respectively. In terms of haplotype and allelic frequencies, the frequencies were not significantly different between ITP and control groups. However, our results showed that -550 C/G genotype might be related to ITP (pvalue: 0.0094; OR: 0.2188; 95% CI: 0.0695-0.6886).

Discussion & Conclusion: The current study is the first report presenting the frequency distribution of six common single nucleotide polymorphisms (SNP) of MBL gene in ITP. Our findings revealed similar findings to previous studies where haplotype LXPA had the oldest evolutionary background. No polymorphisms were detected in +4 C/T, +223 C/T, and +239 G/A. Similarities can be found in the Chinese populations. Most of the frequencies were equally distributed between the ITP and control groups. Polymorphism of -550 C/G among ITP patients has not been studied previously. However, the SNP is relatively common with infectious disease in Chinese paediatric patients. This study had several limitations. First, the current patient samples were barely enough to consider as a large sample size. Furthermore, the samples were obtained from a single facility, so our results are unlikely to be representative of the Kelantanese population. Second, we did not define the relationship between genotype-phenotype of MBL. Therefore, we do not know whether MBL expressions are directly linked to such polymorphisms in ITP patients. Our results indicate that the MBL -550 C/G genotype might be related to ITP. We highlight the importance of prospective studies to confirm the observations from this study.

L1


Ab

stract - La

bo

rato

ry Resea

rch

L2

CHROMOSOMAL ABNORMALITIES IN CHRONIC LYMPHOCYTIC LEUKAEMIA PATIENTS TREATED IN HOSPITAL AMPANG, SELANGOR

Jerome Tan Tsen Chuen1, Ho Kim Wah1, Sharifah Shahnaz Alkudsi1, Chow Lai Chee1, Lee Bee Sun2, Ong Tee Chuan1, Tan Sen Mui1

1Department of Haematology, Hospital Ampang Selangor; 2Faculty of Medicine and Heath Sciences, Universiti Tunku Abdul Rahman

[email protected]

Background: Chromosomal abnormalities are seen in about 80% of Chronic Lymphocytic Leukaemia (CLL) patients and may confer prognostic information and determine potential therapeutic options. A patient’s prior treatment status may offer a clue to the type of chromosomal abnormalities commonly seen in CLL.Objectives: This retrospective analysis aims to look at the incidence and type of chromosomal abnormalities seen in treatment naive and previously treated CLL.

Materials and Methods: A total of 20 CLL patients followed up in Hospital Ampang Selangor between March 2020-September 2021 were randomly chosen for florescence in situ hybridization (FISH) testing at Subang Jaya Medical Centre prior to commencing treatment. The FISH testing was kindly sponsored by Johnson & Johnson (Malaysia). This FISH panel contains probes to 4 common abnormalities seen in CLL namely 17p13.1 (TP53), 13q14.2 (D13S319), 11q22.3 (ATM) and CEP12 (D12Z3).

Results: These 20 patients were diagnosed with CLL between 2002 and 2021. The median follow up is 4.3 years (0.6-19.7) at data cutoff date, death or last known follow-up. Median age at diagnosis was 56.5 years (31-80) with 70% (14) males and 30% (6) females. 80% (16) of the patients had at least 1 chromosomal abnormality and among these, 70.6% (12) had Del13q, 23.5% (4) Del17p, 17.6% (3) trisomy 12 (CEP12) and 11.8% (2) Del11q. These are not mutually exclusive as 4 patients had ≥2 chromosomal abnormalities. Among the 11 treatment naive patients, 54.5% (6) had Del13q, 18.2% (2) trisomy 12 and 27.3% (3) had no abnormality. Among the 9 patients who had prior therapy, 44.5% (4) had Del17p, 22.2% (2) Del11q, 22.2% (2) Del13q as the sole abnormality and 11.1% (1) had no abnormality. 75% (3) of those with Del17p and 50% (1) of those with Del11q also had concomitant Del13q.

Discussion: Among all the patients tested, Del13q is the most common CLL chromosomal abnormality seen at 70.6%. Treatment naive patients did not harbour Del17p or Del11q. In contrast, among previously treated patients, 66.7% (6) had either Del17p or Del11q. The presence of these poor risk chromosomal abnormalities are commonly associated with prior therapy and confer chemoimmunotherapy resistance. Among the therapies received by the previously treated patients, 77.8% were exposed to Chlorambucil, 44.4% Rituximab and 33.3% Fludarabine.

Conclusion: The findings of this study is consistent with established data. CLL patients with prior therapy are at a higher risk of developing poor risk chromosomal abnormalities, consistent with clonal evolution or selection. Genomic testing should be offered to all patients who relapse after their initial therapy and be considered for novel targeted therapies which are known to be effective against poor risk disease.


Ab

stract - La

bo

rato

ry Resea

rch

Ab

stract - La

bo

rato

ry Resea

rch

L3

CLOT WAVE ANALYSIS (CWA) PARAMETERS IN PATIENT WITH PROLONGED IMMOBILIZATION

Rosmaniza Muhamat Yusoff 1,2, Salfarina Iberahim 1,2, Noor Haslina Mohd Noor 1,2 Rosline Hassan 1,2

1Department Haematology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia;2 Hospital Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia

[email protected]

Background: Prolonged immobilization is a well-known risk factor for thromboembolism. This study aims to determine the clot waveform analysis (CWA) in a patient with prolonged immobilization and evaluate the clot waveform pattern We also intended to determine the clot waveform pattern between day one of hospital admission and after three days and above of period of immobilization.

Methods: A total of 30 samples of immobilized patient from Hospital USM were recruited for this study. The plasma from patient was taken on day one of admission and repeated after a period of immobilization (day three and above). The coagulation profile (Prothrombin Time, PT and Activated Partial Thromboplastin Time, aPTT) was performed using ACL TOP 300 CTS (Bedford,USA) coagulation analyser. This analyser uses an optical method. 20 normal control that was recruited from a healthy normal donor were used. The clot waveform generated during the clot formation for PT and aPTT for day one and day three and above was then analysed. Descriptive analysis was used for the reference range. For the comparison of clot waveform analysis between healthy controls and prolonged immobilization patients, Mann-Whitney test was used for data that was not normally distributed and the comparison of clot wave pattern between day one and day three and above of immobilization, paired t-test was used. This study was approved by Universiti Sains Malaysia Research Ethics Committee (JePeM code: USM/JEPeM/20010032) and carried out in accordance with the Declaration.

Result: Mean PT and aPTT for healthy control were 11.66 seconds and 33.98 seconds, respectively. There was no significant difference in mean PT and aPTT between patients and controls. However, the mean CWA parameters were significantly higher among patients with prolonged immobilization than controls, which were the delta change, peak time velocity and height velocity for PT. While for aPTT CWA, the delta change and height velocity were higher than controls. PT CWA parameters among patient with prolonged immobilization showed no significant difference between day one and day three of immobilization, while for aPTT CWA, all parameters were higher in day three except for time of endpoint.

Discussion and conclusion: This study looks into the potential utility of CWA parameters to detect hypercoagulable state in patients who are at risk of developing acute VTE. Clot waveform parameters of both PT and aPTT were analysed in these patients serially at day one and after day three of immobilization. We managed to study four PT parameters from the curve i.e the length of baseline, endpoint, delta change and maximum velocity (peak time velocity and height velocity). For aPTT CWA parameter, the baseline length, endpoint, delta change, maximum velocity (peak time velocity and height velocity), and peak time acceleration were analysed.Patients with prolonged immobilization had elevated PT and aPTT CWA parameters compared to controls. CWA parameters may help to recognize patient at high risk of developing thrombosis. However, more study is needed to explore in this area.


Ab

stract - La

bo

rato

ry Resea

rch

L4

COMPARISON STUDY ON VIABILITY AND RECOVERY OF CD34+ HAEMATOPOIETIC STEM CELLS CRYOPRESERVED WITH 5% AND 10% DIMETHYLSULFOXIDE (DMSO)

Nur Zainura Mohamad1, Habsah Aziz2, Nurasyikin Yusof1,2, S Fadilah S Abdul Wahid3, Suria Abdul Aziz1,2

1 Department of Pathology, Hospital Canselor Tuanku Muhriz, Cheras, Kuala Lumpur, Malaysia; 2Stem Cell Transplant Laboratory, Hospital Canselor Tuanku Muhriz, Cheras, Kuala Lumpur; 3Cell Therapy Centre, Hospital Canselor Tuanku Muhriz, Cheras, Kuala Lumpur, Malaysia

[email protected]

Background: Cryopreservation is a technique of cold-temperature bio-preservation of living cells, tissue, and organs. Cryoprotective compounds such as Dimethylsulfoxide (DMSO), is well known to be cytotoxic and may compromise cell functionality. This study aims to compare the optimum cryoprotective concentration to maintain the quantity and quality of haematopoietic stem cells.

Material and Methods: This study was done on 24 samples of haematopoietic stem cells, collected in a period of 1 year. The haematopoietic stem cells were cryopreserved in cryovials with two different concentrations of DMSO, 5% (n=24) and 10% (n=24). The parameters studied were CD34+ cell count, viability, and recovery; measured before cryopreservation, at day-7 and at day-30 of cryopreservation. The CD34+ cell count and viability were quantified using Stem-Kit ReagentsTM by Beckman Coulter. This kit uses dual color CD45-FITC/CD34-PE murine monoclonal reagent for detection of CD34+ stem cell and 7-aminoactinomycin D (7-AAD) for viability study. The sample were analysed using Beckman-Coulter CytoFLEX flow cytometer, employing the ISHAGE gating strategy.

Results: At Day-7, the CD34+ stem cells cryopreserved in 5% DMSO shows higher absolute viable CD34+ cell count (median=769.8cells/ul, range 140.3-3860.5, p=0.01) as compared to 10% DMSO (median=556.3cells/ul, range 142.2-2588.0). The Day-7 CD34+ recovery in 5% DMSO is also higher (64.3±28.1%, p=0.000) than 10% DMSO (53.8±20.3%). At day-30, the median for absolute viable CD34+ cell count is 711.4cells/ul (range 124.0-2941.3) for PBSC in 5% DMSO and 523.8 cells/ul (range 124.4-2924.6) in 10% DMSO (p=0.007). The CD34+ cell recovery at day-30 is significantly better for PBSC in 5% DMSO (59.8±26.1%, p=0.005) as compared to 10% DMSO (45.8%±16.6%). No significant difference (p>0.05) in the CD34+ cells viability between PBSC in 5% and 10% DMSO, at day-7 and day-30 of cryopreservation. No statistically significant degradation in the absolute viable CD34+ cell count, CD34+ viability and CD34+ cell recovery (p>0.05) were seen at day-30 as compared to day-7 for samples cryopreserved in 5% and 10% DMSO concentration.

Discussion & Conclusion: Significantly better CD34+ cell count and recovery, with no significant degradation of graft quality seen in haematopoietic stem cells cryopreserved in 5% as compared to 10% DMSO concentration. In conclusion, we have shown that DMSO 5% appear to be a safe and reasonable substitute to the current practice of using DMSO 10% as a cryoprotective agent.


Ab

stract - La

bo

rato

ry Resea

rch

Ab

stract - La

bo

rato

ry Resea

rch

L5

CYTOGENETIC FINDINGS AND ITS CORRELATION WITH OVERALL SURVIVAL (OS) AND EVENT FREE SURVIVAL (EFS) IN PATIENTS WITH AML

Qhasmira Abu Hazir1, Raja Zahratul Azma Raja Sabudin1, Azlin Ithnin1, Nor Rafeah Tumian2 , Salwati Shuib1

1 Department of Pathology, Faculty of Medicine, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia Medical Centre, 56000 Kuala Lumpur, Malaysia2Department of Medicine (Hematology Unit), Faculty of Medicine, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia Medical Centre, 56000 Kuala Lumpur, Malaysia

Correspondence to: Salwati ShuibDepartment of Pathology, Faculty of Medicine, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia Medical Centre, 56000 Kuala Lumpur, Malaysia

[email protected] Background: Acute myeloid leukemia (AML) is a heterogeneous disease in terms of cytogenetics and molecular genetics. AML is the most common acute leukemia in adults and its incidence increases with age. Diagnostic cytogenetics is an important prognostic indicator for predicting outcome of AML. Therefore, stratification of de novo acute myeloid leukemia (AML) based on demographic and cytogenetic profile is very crucial for effective treatment and to predict survival in the patients.

Objectives: The main objective of this study is to study the clinical profiles, cytogenetics/fluorescence in situ hybridization (FISH), outcomes with the standard of care treatment on patient and evaluate the prognostic importance of cytogenetic abnormalities of adult de novo acute myeloid leukaemia cases in Hospital Canselor Tuanku Muhriz (HCTM), Cheras, Malaysia.

Materials & Methods: In this observational study, retrospective analysis was performed by examining the karyotypic patterns/FISH of 91 adult patients with de novo AML seen at our centre and evaluated the association of cytogenetic/FISH risk stratification with the age, overall survival (OS) and event free survival (EFS) of patient. Results: Data of 91 adult patients who had de novo AML were analyzed. The mean age at diagnosis in our study was 54 years old. A total of 63 patients (69.2%) were treated with intensive induction chemotherapy and among these patients 58 (92%) yielded karyotype/FISH results. Chromosome abnormalities were detected in 17 patients (18.7%). The most common cytogenetic abnormality in our study was trisomy 8, followed by hypodiploidy (<46 chromosome) and hyperdiploidy (>46 chromosome). The age group of 15-60 years old had the highest frequency of normal karyotype (60.3%) compared to 61 years old and above. The complex karyotype was found with the highest frequency (100%) in age group above 61 years old and above when compared to age group ≤60 years old. Different cytogenetic abnormalities in AML show different frequencies with increasing age.

Discussion: There was no statistically significant difference of overall survival (OS) between the intermediate and the poor cytogenetics group (mean survival time: 14 versus 2.5 months, 5 years OS 13% versus 10%; p-value = 0.374). A similar finding was observed for event free survival (EFS) [mean survival time: 10.6 versus 2.0 months, 5 years EFS 15% versus 10%; p-value = 0.554].

Conclusion: In conclusion, this study showed complex karyotype is common in older patients (61 years old and above) while normal karyotype is usually found in younger patients (≤60 years old). There was no statistically significant difference of overall survival (OS) between the intermediate and the poor cytogenetics group. Larger sample size is recommended for future study to determine correlation between karyotypes and survival among the AML patients.


Ab

stract - La

bo

rato

ry Resea

rch

L6

CYTOPEUTICS® HUMAN UMBILICAL CORD MESENCHYMAL STEM CELLS (hUC-MSCS): CELL TRANSDUCIBILITY, IN VITRO INVESTIGATIONS AND BIODISTRIBUTION IN BALB/C MICE

Marini Marzuki1#, Lihui Tai2#, Nurul Ashikin Mohamed Shahrehan1, Christine Ricky1, Nur Izzati Mansor2, Mohd Noor Syuhada Md. Halim1, Audrey Fanty1, Annas Salleh3, Chui Thean Low1, Alan Soo Beng Khoo4, Susan Ling Ling Hoe1, Sze-Piaw Chin2

1Molecular Pathology Unit, Cancer Research Centre, Institute for Medical Research, NIH, Setia Alam, Selangor, Malaysia; 2Cytopeutics Sdn. Bhd., Cyberjaya, Selangor, Malaysia; 3Department of Veterinary Laboratory Diagnosis, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Selangor, Malaysia, 4Centre for Cancer and Stem Cell Research, Institute for Research, Development and Innovation, IMU, Malaysia #equal contribution

Corresponding authors:[email protected] (Cytopeutics)[email protected] (IMR)

Background: Mesenchymal stem cells (MSCs) are the targets of one of the most promising cellular therapies in recent years due to their profound immunomodulatory, anti-inflammatory, and regenerative attributes. MSCs can be isolated from various parts of the human body such as adipose tissue, bone marrow, umbilical cord, umbilical cord blood, and placenta. Cytopeutics® has obtained allogeneic MSCs derived from the umbilical cord tissues, which had demonstrated safety and efficacy in clinical studies involving healthy and subjects with liver cirrhosis, diabetes, and knee articular cartilage defect. Although the safety and efficacy of Cytopeutics® hUC-MSCs have been studied, the data with regard to the biodistribution and fate of Cytopeutics® hUC-MSCs are still not well explored. Here, we aimed to demonstrate the transducibility of Cytopeutics® hUC-MSCs by lentiviral vectors and to explore the biodistribution, as well as clearance of Cytopeutics® hUC-MSCs in healthy BALB/c mice, following intravenous administration.

Materials and Methods: gfp-luc2 gene expression cassette was first transfected into producer HEK293T cells, followed by transduction via lentivirus into recipient hUC-MSCs. Green fluorescent protein (GFP) expression was tracked by microscopy for up to 72 h and by flow cytometry on day 0, 7 and 14 post-transductions. Immunophenotypic analysis of MSC markers (CD44, CD105, CD73 and CD90) was evaluated on parental (non-transduced) and transduced Cytopeutics® hUC-MSCs by flow cytometry. Biodistribution of transduced Cytopeutics® hUC-MSCs in BALB/c mice was tracked by IVIS imaging on a daily basis.

Results: GFP expression in transduced Cytopeutics® hUC-MSCs was first detectable by microscopy at 24 h post-transduction, with the signal gaining intensity by 72 h. Throughout in vitro culture of the transduced cells, GFP expression level had decreased from 73.1 ± 5.5 % (day 0) to 40.5 ± 1.4 % (day 14). The transduced Cytopeutics® hUC-MSCs retained MSC surface marker expression similar to the parental Cytopeutics® hUC-MSCs. Upon tail vein intravenous administration into healthy BALB/c mice, the transduced cells migrated to and localized at the lungs as early as 1 h post-administration. These cells were continuously detected in the lungs via IVIS imaging for up to 3 days before being cleared from the body.

Discussion & Conclusion: Cytopeutics® hUC-MSCs were transducible by lentivirus with relatively high uptake of the GFP-Luc2 exogenous proteins. GFP signal (encoded by gfp reporter gene) provided a fluorescent visualization of transduced cells as shown in this study, whereas luciferase (encoded by luc2 reporter gene) in living cells can react chemically with luciferin to provide a luminescent signal. Lentiviral transduction does not seem to disrupt the cellular morphology and protein expression of MSC markers in theCytopeutics®

hUC-MSCs. Infused GFP-Luc2 transduced hUC-MSCs localized predominantly in the lungs of BALB/c mice, as commonly reported for MSCs in other studies. In conclusion, Cytopeutics® hUC-MSCs can be successfully transduced via lentivirus and the transduced cells were still able to be localized at predominant organ(s) after infusion into BALB/c mice.


Ab

stract - La

bo

rato

ry Resea

rch

Ab

stract - La

bo

rato

ry Resea

rch

DELINEATION OF THE MOLECULAR BASIS OF BORDERLINE HAEMOGLOBIN A2 IN MALAYSIAN POPULATION

Norafiza Mohd Yasin1, Nur Fatin Aqilah Raman1, Durar Aqilah Zamri, Lailatul Hadziyah Mohd Pauzy, Faidatul Syazlin Abdul Hamid1, Nur Aishah Aziz1, Syahzuwan Hassan1, Ermi Neiza Mohd Sahid1, Yuslina Mat Yusoff1, Ezalia Esa1

Haematology Unit, Cancer Research Centre, Institute for Medical Research (IMR), National Institutes of Health, Setia Alam, Malaysia.

IntroductionThe identification of the β-thalassaemia carrier relies on the elevated Hb A2 level (HbA2). HbA2 level of (>4.0%) is considered the most reliable hematologic finding for the presumptive diagnosis of β-thalassemia carriers. The ‘grey zone’ of borderline haemoglobin A2 (HbA2) levels may pose a diagnostic challenged as their HbA2 levels are below cut off point could be due to co-inheritance of α- or β-thalassaemia that might affect the levels. Currently, limited data available describing the molecular basis of borderline HbA2 in the Malaysian population particularly.

ObjectiveThis study aimed to characterise and delineate the common genotypes involved in borderline HbA2 thalassaemia and to determine the significant cut off HbA2 level that required further molecular analysis to rule out β-thalassaemia.

Materials and methodRetrospective analysis of 2886 cases from January 2017 to December 2020 with borderline HbA2 ranges from 3.0% to 3.9% based on either capillary electrophoresis (CE) and High-Performance Liquid Chromatography (HPLC) were collected. The samples were further divided into two groups. First group with HbA2 level of 3.0-3.4% and the second group with HbA2 level of 3.5-3.9%. Samples with borderline HbA2 level and normochromic normocytic red cell indices were analysed separately. Results of haematological parameters and Hb analysis were reviewed. All the samples were analysed with conventional multiplex amplification refractory mutation system (β-MARMS) and HBB gene sequencing. Selected cases will proceed with α-GAP and ARMS-PCR, alpha triplication and HBD gene sequencing based on their haematological parameters and Hb analysis. Statistical analysis was conducted using SPSS version 26. A Receiver Operating Characteristic (ROC) analysis was performed to determine sensitivity and specificity of HbA2 in genotype determination within the 3.0 to 3.9% interval.

ResultsAmong 589 subjects in 1st group with HbA2 level of 3.0-3.4%, 203 (35%) was positive for a molecular defect in the α-, ß- and and δ-globin genes, with majority of the samples (62.7%, n=370) have no abnormality detected in both genes. For 2nd group with HbA2 level of 3.5-3.9% (n=1142), majority of the samples have significant beta mutation (52.23%, n=596), 54 cases (4.73%) with β-mutation co-inherited with alpha and α-mutation (37.51%, n=428). As expected, different mutation spectrums of borderline β-thalassaemia were found in this study as compared to genotype spectrum of classical β-thalassaemia and surprisingly, α-thalassaemia alone involved in significant numbers of samples with raised HbA2 level. The data also showed the cut off HbA2 level that currently used for definition of borderline HbA2 beta thalassaemia (HbA2 of 3.3%) will give 94% sensitivity with 30% sensitivity while lowering the cut off value to 3.2% will increased the sensitivity to 96% with 20% specificity.

ConclusionThe borderline HbA2 β-thalassaemia is not a rare event in our country. Based on our findings, the prevalence of borderline HbA2 β-thalassaemia is around 40%. The chosen cut off value will affect the sensitivity and specificity of the molecular test. Our findings showed according to the evaluation of both MCV/MCH and HbA2 level, it is possible to differentiate mild mutations from more severe β-globin gene defects.

Keywords: Borderline HbA2, β-thalassemia, Cut-off value

L7


Ab

stract - La

bo

rato

ry Resea

rch

L8

DOWNREGULATIN OF hsa-miR-548d-3p AND OVEREXPRESSION OF HOXA9 IN DIFFUSE LARGE B-CELL LYMPHOMA PATIENTS AND THE RISK OF R-CHOP-CHEMOTHERAPY RESISTANCE/DISEASE PROGRESSION

Choo-Yuen Ting1, Soo-Yong Tan2, Gin-Gin Gan1, Shamsul-Mohd Zain3, Yuh-Fen Pung4, Diana Bee-Lan Ong5, Ping-Chong Bee1

1. Department of Medicine, Faculty of Medicine, University of Malaya, Malaysia. 2. Department of Pathology, National University of Singapore, Singapore.3. Department of Pharmacology, Faculty of Medicine, University of Malaya, Malaysia 4. Division of Biomedical Science, University of Nottingham Malaysia, Malaysia5. Department of Pathology, Faculty of Medicine, University of Malaya, Malaysia.

[email protected]@gmail.com

Background: Routine categorization of DLBCL patients into GCB and non-GCB groups by Hans’ criteria could not accurately predict chemoresistance or disease progression in patients treated with standard R-CHOP therapy. There is a need to identify better biomarker predictors to enhance assisted selection of chemotherapy regimens for DLBCL patients.

Objective: To identify dysregulated miRNAs and mRNAs that are predictive of resistance to R-CHOP chemotherapy or disease progression in patients with DLBCL.

Materials and methods: miRNA and mRNA profiling were performed on archival FFPE samples of the DLBCL patients. miRabel and miRNet bioinformatic tools were applied to determine experimental validated miRNA-mRNA target interaction; and the bioinformatic results were validated by miRNA-mediated gene silencing experiment on the OCI-LY3 cell line (ABC subtype-DLBCL cells). The significance of the genomic predictive values was assessed using adjusted odds ratios (AOR) and 95% confidence intervals (CI).

Results: 19/36 were R-CHOP therapy-resistant whilst 17/36 were R-CHOP therapy-sensitive. Ten dysregulated miRNAs and 12 dysregulated mRNAs were identified in therapy-resistant DLBCL patients. These dysregulated miRNAs and mRNA cause therapy resistance and disease progression in DLBCL patients, most likely via dysregulation of p53 pathway, upregulation of the anti-apoptotic protein bcl2 triggered by altered expression of LIF, HOXA11, RB1, HOXA9 and PRMT8 mRNAs, activation of the JAK/STAT signaling pathway attributed to increased expression of IL-13 and LIF cytokines, transcriptional misregulation of HOXA9 and HOXA11, upregulation of transcription factors (FOXL2, GATA2), and downregulation of tumour suppressors (RB1, PHF6).

Of all the dysregulated miRNAs and mRNAs detected, downregulation of hsa-miR-548d-3p and overexpression of HOXA9 mRNA was found to be an independent risk factor for R-CHOP chemotherapy resistance/ disease progression in DLBCL patients [hsa-miR-548d-3p AOR: 0.258, 95% CI: 0.097-0.684, P=0.006]. The tumour suppressor hsa-miR-548d-3p has been identified as the regulator of HOXA9 mRNA in DLBCL cancer cells.

Discussion:Genetic heterogeneity of DLBCL disease is evident in this study. Dysregulation of hsa-miR-548d-3p/HOXA9 is a potential biomarker fork risk prediction in DLBCL patients, independent of R-IPI score. Dysregulation of this hsa-miR-548d-3p/HOXA9 not only triggers cancer cells growth, but also induces the expression bcl-2 anti-apoptotic protein; which in turn, leads to therapy resistance. Therefore, this group of patients may benefit from bcl-2 anti-apoptotic inhibitor such as Venetoclax (ABT-199) or BM-1197 (bcl-2 and Bcl-xl dual inhibitor). Conclusion: DLBCL patients with downregulation of hsa-miR-548d-3p and overexpression of HOXA9 mRNA are more likely to experience R-CHOP therapy resistance and disease progression. This biomarker may be used as a complementary tool to the R-IPI score to risk stratify DLBCL patients.


Ab

stract - La

bo

rato

ry Resea

rch

Ab

stract - La

bo

rato

ry Resea

rch

L9

EXTENDED RBC PARAMETERS IN LATENT IRON DEFICIENCY AMONG BLOOD DONORS IN HOSPITAL USM

Sivanesan Sockalingam1,2, Rosnah Bahar1,2, Zefarina Zulkafli1,2

1 Department of Haematology, School of Medical Sciences; 2 Transfusion Medicine Unit, Hospital USM, Universiti Sains Malaysia, Kubang Kerian, Malaysia

[email protected]

Background: Timely detection and treatment of latent iron deficiency (LID) can prevent the development of iron deficiency anaemia. This is important in populations that are at risk like regular donors and women of reproductive age. Standard RBC parameters fall short in the investigation of LID as their values are not significantly different from normal subjects. The extended RBC parameters RET-He (reticulocyte haemoglobin equivalent), MicroR (percentage of microcytic RBC <60fL), and HYPO-He (percentage of hypo-haemoglobinised RBC <17pg) may aid in the screening of latent iron deficiency. The objective of this study is to compare the level of MicroR, Hypo-He and RET-He between normal and LID.

Materials and Methods: This was a prospective case-control study performed on blood donors in Hospital USM from August 2021 to February 2022. Inclusion criteria were blood donors who were eligible to donate based on the guideline set by the Transfusion Unit, Hospital USM. Exclusion criteria were reactive donors and postmenopausal women. Subjects are classified into latent iron deficiency group and control group based on their serum ferritin level. Donors with MCH≤27pg are excluded from the control group because of possible thalassemia or hemoglobinopathy. Standard RBC parameters (RBC, Hb, HCT, MCV, MCH, MCHC, RDWSD, RDWCV) and extended RBC parameters (RET-He, MicroR and HYPO-He) were measured using XN-1000 (Sysmex, Kobe, Japan) while serum ferritin was measured using ARCHITECT i2000SR (Abbott, Illinois, U.S.A.). Normality testing and comparison were done between the groups for the extended RBC parameters.

Results: There were 89 (32%) donors with latent iron deficiency and 193 (68%) donors in the control group. Most of those with LID were regular donors (96%). All the parameters except RDWSD for LID were non-parametric. The control group’s median (IQR) value for RET-He, MicroR and HYPO-He were 31.8pg (1.6pg), 2.5% (2.3%) and 0.2% (0.2%) respectively. For LID, the values were 30.4pg (2.6pg), 4.5% (6.9%) and 0.5% (1.3%) respectively. All the extended RBC parameters were significantly different at p<0.001 between LID and control.

Discussion & Conclusion: The extended RBC parameters differ significantly between LID and normal. These parameters can be measured with faster turn-around-time and at lower cost compared to serum ferritin. The limitation of this study is the possible presence of concomitant thalassemia or hemoglobinopathy in the LID group. In conclusion, RET-He, MicroR and HYPO-He can be considered as screening tool in the evaluation of latent iron deficiency.


Ab

stract - La

bo

rato

ry Resea

rch

L10

FREQUENCY AND CLINICAL IMPLICATION OF ADDITIONAL CHROMOSOMAL ABNORMALITY IN ADULT PHILADELPHIA CHROMOSOME POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA

Phan Chin Lee1,2,4, Subramanian Yegappan1, Khang Tsung Fei2, Leong Tze Shin1,3, Ng Ching Ching4

1Clinical Haematology Referral Laboratory, Department of Haematology, Hospital Ampang, Selangor, Malaysia; 2Institute of Mathematical Sciences, Faculty of Science, University of Malaya; 3Sarawak General Hospital, Kuching, Sarawak; 4Genetics and Molecular Biology, Institute of Biological Sciences, Faculty of Science, University of Malaya

[email protected]

Background: The impact of an additional chromosomal abnormality (ACA) on survival outcome in adults with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) remains controversies. The impact of ACA on prognostic impact in Malaysian Ph+ ALL population is still limited.

Materials & Methods: We conducted retrospectively study to characterize the ACA associated with t(9;22) and assess the recurrent ACAs provide any additional prognostic information on survival outcome in 51 adult Ph+ ALL patients.

Results: Overall, 60.8% (n=31) of patients had ACA. The recurrent types of ACAs included +der(22)t(9;22) [n=9, 29.0%], gain of 8q/+8 (n=6,19.4%) and -7 (n=5, 16.1%) were occurred frequently in 5 or more patients. Nine patients with variant t(9;22) translocation (29.0%), which t(3;9;22) was most frequent detected. Monosomal karyotype (MK) were found in 38.7% of the recurrent ACAs. The presence of ACAs, particularly +der(22)t(9;22), variant t(9;22) and MK showed a low tendency in overall survival and event-free survival rates compared to the isolated Ph group, when investigated separately, although the prognostic impact of these ACAs were not significant differences.

Discussion & Conclusion: The chromosome aberrations in adults with Ph+ ALL are heterogenous. With the limited number of patients for each ACA, our results showed the recurrent ACAs particularly extra Ph, variant t(9;22) and MK constitute a group of a tendency of poor risk-ACAs that might reduce OS and EFS, although lack of significant differences associated with the recurrent ACAs on survival outcome in adult Ph+ ALL patients treated with TKI. We suggest that characterisation of ACAs still hold important value to stratify patients into risk-adapted treatment to improve survival prognostication strategies of adult Ph+ ALL.


Ab

stract - La

bo

rato

ry Resea

rch

Ab

stract - La

bo

rato

ry Resea

rch

L11

GENETICALLY ENGINEERED HUMAN UMBILICAL CORD-DERIVED MESENCHYMAL STEM CELLS EXPRESSING HUMAN INTERLEUKIN-12 INHIBIT LUNG ADENOCARCINOMA CELLS IN VITRO

Jiunn Jye Goh1,2,4, Hoon Koon Teoh1,4, Hooi Tin Ong1,4, Bee Sun Lee3,4, Soon Keng Cheong3,4

¹Department of Pre-clinical Sciences, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Selangor, Malaysia; 2Department of Research and Development, Cryocord Sdn. Bhd, Selangor, Malaysia; 3Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Selangor, Malaysia; 4Centre for Stem Cell Research, Universiti Tunku Abdul Rahman, Selangor, Malaysia.

[email protected]

Background: Interleukin-12 (IL-12) is a key immunomodulatory cytokine with antitumour effects. However, the systemic administration of IL-12 at therapeutic dosage leads to serious toxicity in cancer patients due to the induction of extremely high systemic level of interferon-γ. Mesenchymal stem cells are promising cellular vehicles for cancer therapy. They are highly amenable to transduction by viral vectors to express and deliver exogenous proteins to tumour sites due to their tumour homing ability. In this work, we transduced human umbilical cord-derived mesenchymal stem cells (hUCMSC) with adenoviral vector expressing hIL-12 and investigated their cytotoxic effects on lung adenocarcinoma cells.

Materials and Methods: The hIL-12 gene was first cloned into linearised pAdenoX-ZsGreen1 using Adeno-XTMAdenoviral System 3. The linearised recombinant adenoviral plasmid was then packaged into recombinant adenovirus using HEK293 cells and further amplified and purified. Viral titers were determined and multiplicity of infection (MOI) 10 was selected to infect hUCMSC in generation of hUCMSC expressing hIL-12 (hUCMSC-IL12). The hUCMSC-12 (1x104 cells/well) were co-cultured with H1975 lung adenocarcinoma cells (1x103/well) in a 24-well transwell system for 5 days. Cell viability of H1975 was determined using CCK-8 assay. Untransduced hUCMSC served as control. Similar co-culture assay was repeated again using MRC-5 human lung fibroblast cells. The supernatant in the co-culture assay were collected for the quantification of hIL-12 level using ELISA.

Results: The cell viability of H1975 showed significant reduction (71.6%) on day 5 after co-cultured with hUCMSC-IL12 while there was no significant difference observed when co-cultured with untransduced hUCMSCs (95%). Interestingly, there was significant increase in the viability of MRC-5 human lung fibroblast cells after 5 days co-cultured with untransduced hUCMSCs (150.4%), but not hUCMSC-IL12 (114.0%). The hIL-12 protein expressed by hUCMSC-IL12 increased from 1.2µg/ml on day 3 to 2.2µg/ml on day 5.

Discussion & Conclusion: From our findings, hIL-12 secreted by hUCMSC-IL12 successfully demonstrated cytotoxic effect on lung adenocarcinoma cells without affecting the viability of human lung fibroblast cells at the same hIL-12 concentration. Hence, genetically engineered hUCMSC expressing hIL-12 using the adenoviral vector can be potentially utilised as cellular vehicles in cancer therapy to overcome the systemic toxicity of IL-12.


Ab

stract - La

bo

rato

ry Resea

rch

L12

HUMAN HB G-MAKASSAR IN MALAYSIA; IS IT COMMON?

Ezalia Esa1, Roszymah Hamzah2, Norafiza Mohd Yasin1, Faidatul Syazlin Abdul Hamid1, Nur Aisyah Aziz1, Veena Sevaratnam2, Tan Sen Mui2, Ahmad Sabry Mohamad3

1 Institute Research of Malaysia, Shah Alam, Selangor, Malaysia; 2 Ampang Hospital, Ampang, Selangor, Malaysia; 3 UniKL-BMI, Gombak, Selangor, Malaysia

[email protected]

Background: Hb G-Makassar is a β hemoglobin variant exhibited at the β6 or A3 location where the normal glutamyl residue is replaced by an alanyl residue (β6 Glu→Ala). There are limited data on Hb G-Makassar and its associated variants in Malaysia. The aim of this study was to investigate the prevalence of Hb G-Makassar in Malaysia, to study the genomic and phenotype of each variant.

Materials and Methods: This was a retrospective cohort study of all patients diagnosed with β-thalassemia from January 2014 to December 2021 at the Institute for Medical Research (IMR), Malaysia. The Hb analysis was obtained from blood samples undergoing routine and screening hemoglobin checking at the various hospital. The presumptive diagnosis of beta chain variant mainly Hb Sickle were made based on Hb analysis findings. Genomic DNAs were extracted from peripheral blood and the globin genes were analyzed by using direct sequencing of HBB gene. The multiplex gap PCR was carried out to rule out single gene deletions (-α3.7 and -α4.2) and double gene deletions (--SEA, --MED and –α20.5) while the multiplex ARMS-PCR was used to detect non-deletional alpha thalassaemia (Hb Constant Spring ATG→A–G), Hb Quong (∆GAC) and Hb Adana (TCC→CCC).

Results: A total of 38 patients were identified with Hb G-Makassar mutation. There were 14 (36.8%) males and 24 (63.2%) females. Interestingly, all were of Malay ethnicity with a mean age of 20.34 ± 8.78 years. Majority, (n=23, 60.5%) were detected from National Form 4 screening program. Six Hb G-Makassar variants were identified; heterozygous Hb G-Makassar (n=19, 50.0%), compound heterozygous Hb G-Makassar/HbE (n=4, 10.5%), compound heterozygous Hb G-Makassar/Hb New York (n=1, 2.6%), heterozygous Hb G-Makassar with co-inheritance Hb Adana (n=2, 5.3%), heterozygous Hb G-Makassar co-inheritance with single alpha deletion (n=11, 28.9%) and heterozygous Hb G-Makassar co-inheritance with--SEA deletion (n=1, 2.6%). Most of the patients (n=20) were from Terengganu. At the last follow-up, all patients are alive, asymptomatic, non-transfusion dependent and did not show any complications.

Discussion & Conclusion: Hb G-Makassar is a rare disease with limited information reported. This is a large cohort of patients with Hb G-Makassar found in Malaysia, which showed specific geographical distribution and found exclusively among Malay ethnicity. Several variants were identified but all of them have either mild phenotype or asymptomatic. This study also provides a valuable reference for prenatal diagnosis and genetic counseling as well as data to support the optimization of novel sickle cell disease therapy. Recently, it has been reported that conversion of sickle hemoglobin (HbS) to Hb G-Makassar is a promising new treatment option that may assist in gene editing therapy in patients with sickle cell disease. In conclusion, our findings on this rare mutation is important to decoding the epidemiological background of beta thalassaemia in Malaysia.


Ab

stract - La

bo

rato

ry Resea

rch

Ab

stract - La

bo

rato

ry Resea

rch

L13

MOLECULAR INTERROGATION OF CHRONIC MYELOID LEUKAEMIA PATIENTS WHO FAILED SECOND GENERATION TYROSINE KINASE INHIBITOR USING NEXT GENERATION SEQUENCING

Siew Lian Chong1, Asral Wirda Ahmad Asnawi1, 2, Tien Gen Wong1, Pek Kuen Liew2, Sharifah Shahnaz Syed Abd Kadir1, Tee Chuan Ong1, Jerome Tan1, Kim Wah Ho1, Veena Selvaratnam1, Subramanian Yegappan1, Sen Mui Tan1

1Department of Hematology, Hospital Ampang, Selangor, Malaysia.2Faculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia, Negeri Sembilan, Malaysia.

[email protected]

Background: The practise of prescribing Chronic Myeloid Leukaemia (CML) patients with indefinite tyrosine kinase inhibitors (TKIs) has gone uncontested, and the capacity of TKIs to eliminate the CML clone is also still unknown. Although the vast majority of CML patients do respond to TKIs, nonetheless, resistance may develop either de novo or during treatment. TKI resistance pathways are commonly classified as BCR-ABL1-dependent or BCR-ABL1-independent. The molecular evolution causal for this subset of individuals to lose molecular remission is still unknown. In this study, our goal was to explore the molecular mechanisms involved in resistance to TKI in patients who failed second-generation TKIs in order to identify potential genetic signatures and pathways that lead to TKI resistance.

Materials and Methods: CML patients who failed second generation TKI were identified and labeled as non-responders. Eight RNA samples were analysed for purity and processed using the Illumina Stranded Total RNA Prep, Ligation with Ribo-Zero Plus kit (Illumina, CA, USA) according to manufacturer’s instruction. Samples were sequenced on Illumina Novaseq 6000 system (Illumina, CA, USA) system with an average of approximately 133 million passed paired reads, 100 bp in length, per sample. The paired-end reads were aligned to the human reference genome (version hg38/GRch38) using the Illumina DRAGEN (Dynamic Read Analysis for GENomics) Bio-IT Platform. The same system was used for gene-expression quantification, fusion gene detection, and variants analysis. Genes that demonstrate Log2 fold-change ≥3 and P≤0.01 were identified as differentially expressed genes (DEGs). The significantly enriched pathways from several pathway databases were filtered at a false-discovery rate (FDR) of <0.01.

Results: BCR-ABL1 was detected in all non-responders. TPM4-KLF2, and CCDC32-CBX3 were the next most common gene fusions found in non-responders (5 out of 8). A total of 21,782 (or around 3.5%) variations were determined to be present only in non-responders. There were a total of 201 DEGs discovered, with 87 genes up-regulated and 114 genes down-regulated in the non-responder group. The DEGs were enriched in the Histone acetylation/deacetylation (HDACs/HATs), cellular senescence, and the RNA polymerase regulatory pathway.

Discussion & Conclusion: Techniques with enhanced sensitivity such as next-generation sequencing and the use of artificial intelligence techniques coupled with the development of mathematical modelling and computational prediction methods could reveal the underlying mechanism of drug resistance and facilitate the design of more effective treatment strategies for improving drug efficacy in CML patients. This preliminary analysis found that individuals who failed second-generation TKIs express a potentially unique genetic signature. Analysis using larger sample size is necessary to validate these findings.


Ab

stract - La

bo

rato

ry Resea

rch

L14

MOLECULAR LANDSCAPE OF CASES WITH BORDERLINE HBA2 LEVELS IN HOSPITAL CANSELOR TUANKU MUHRIZ

Lailatul Hadziyah Binti Mohd Pauzy1, Raja Zahratul Azma1, Azlin Ithnin1, Rini Albert2, Hafiza Alauddin1

1Department of Pathology; 2Laboratory Diagnostic Services, Faculty of Medicine, Hospital Canselor Tuanku Muhriz Universiti Kebangsaan Malaysia (HCTM UKM), Kuala Lumpur, Malaysia

[email protected]

Background: Thalassaemia is a prevalent genetic disease in Malaysia affecting up to 6% of the population. An elevated HbA2 reading (>4%) is among the most important parameter for the identification of beta (β) thalassaemia carriers. However, many studies have shown that some cases with the HbA2 in the borderline range between 3.0% to 3.9% harbor either alpha (<), beta (β) globin and/or KLF1 gene abnormalities too. Without molecular analysis, the carrier status of these patients may be missed. If a carrier of the disease has a child with another carrier, there is a high chance of producing an offspring with thalassemia major and an even higher risk to produce a carrier of thalassemia. Here, we report the results of molecular investigations on a group of subjects with borderline HbA2.

Methods: A total of 45 subjects with borderline HbA2 levels were identified from the hematology laboratory archival data from January 2014 to December 2018. results of their full blood count using Sysmex XN-1000, and hemoglobin analysis using Sebia capillary variant II were collected. Their DNA sample were investigated for the presence of locally common pathological mutations in the β globin gene using multiplex amplification-refractory mutation system (M-ARMS) PCR technique. Their < globin gene were screened for common deletions using multiplex Gap-PCR and locally common mutation using M-ARMS technique. High Resolution Melting Point assay was used to screened for KLF1 gene mutation followed by Sanger sequencing for confirmation.

Results: The mean HbA2 level was 3.25% (±0.32%), mean haemoglobin level was 11.97g/L (± 1.49 g/L), mean MCV was 75.94 fl (±9.0 fl) and mean MCH was 24.76 pg (±3.54 pg). A total of 44% (20/45) of the cases with borderline HbA2 in HCTM shows genetic abnormality at the molecular level. β gene only mutation was found in 13 sample, the commonest being Poly A (A>G) mutation. Other β gene mutations found include Cap +1 (A>C), IVS 1-5 (G>C), IVS II-16 (G>C) and IVS 2-654. < gene defect was only seen in four samples, the commonest being -α3.7 deletion. Other < gene defect detected include Hb Constant Spring and Hb Adana mutations. A total of two samples harboured coinheritance of < and β gene defects. More interestingly, a new KLF1 gene variant (c.633 G>C) was also discovered in two samples.

Discussion & Conclusion: Borderline HbA2 cases are not uncommon especially in endemic region such as Malaysia. Our study found a higher frequency of borderline HbA2 cases as compared to most of the previously published literatures. The types of mutation discovered are also unique to our centre as compared to other local studies. On the basis of our findings we strongly suggest molecular methods consisting of β and < globin genes study to be considered in the investigation for hemoglobinopathies in the borderline HbA2 group of patients especially when the individual has a partner who is a β thalassaemia carrier. Further study on KLF1 gene mutation test in our population is paramount to further characterize the common mutations of the gene.


Ab

stract - La

bo

rato

ry Resea

rch

Ab

stract - La

bo

rato

ry Resea

rch

L15

THE HAEMATOLOGICAL, HAEMOSTATIC AND INFLAMMATORY MARKERS IN EARLY SEPSIS BASED ON SOFA SCORE

Fairuz Amil1,3, Salfarina Iberahim1,3, Shafini Mohamed Yusoff1,3, Wan Suriana Wan AB Rahman3,4, Huda Zainal Abidin2,3

1 Department of Haematology, School of Medical Sciences, USM, 16150 Kubang Kerian, Kelantan; 2 Department of Anaesthesiology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia; 3 Hospital Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia; 4School of Dental Sciences, USM, 16150 Kubang Kerian, Kelantan.

[email protected]

Background: Early diagnosis of sepsis is important to reduce the risk of high morbidity and mortality rate in the sepsis patient. Even though microbiological culture has been considered the gold standard for the diagnosing of sepsis, it is time-consuming, and yield can be poor in the patient who previously received antibiotics. Furthermore, the result can be falsely positive due to contamination during inoculation techniques. Because of these limitations, there has been a continuous effort to get effective biomarkers of sepsis with good diagnostic and prognostic yields. The objective of this study is to compare the haematological, haemostatic, and immunological markers between the subjects (high SOFA:>11 scores) and the control group (low SOFA: <8 scores) at Hospital Universiti Sains Malaysia (HUSM).

Materials & Methods: This study was a case-control and retrospective study involving 186 total patients admitted to the Intensive Critical Unit (ICU) (for the cases group) and Medical wards (for the control group) in Hospital Universiti Sains Malaysia (HUSM), Kelantan, from January 2018 until April 2022 and fulfilled the study criteria. The haematological (neutrophil lymphocytes ratio, monocytes, platelet), haemostatic markers (d-dimer, fibrinogen, PT, APTT) and immunological markers (CRP, ESR) were collected from the patient information system. The parameters for sepsis were identified based on Sequential Organ Failure Assessment (SOFA) score. The data were statistically analysed.

Results: The mean differences between the different statuses of SOFA are p<0.001 for neutrophil lymphocytes ratio (NLR), platelet, and CRP while PT is p=0.049. For NLR, participants with SOFA >11 were higher by 13.92 (95% CI=-18.24, -9.61) compared to the control group with SOFA <8. For CRP and PT, participants in the SOFA >11 group had a higher mean compared to SOFA <8 group by 45.11(95% CI=-64.14, -26.09) and 1.15 (95% CI=-2.29, -0.01), respectively. While for platelet, participants in SOFA<8 group have a higher mean value than the SOFA>11 group by 93.09 (95%CI=52.84,133.35).

Discussion & Conclusion: There were statistically significant differences between high and low SOFA groups for NLR, platelet, and CRP (all p<0.001). Thus in this study, a severe sepsis patient (high SOFA score) has high NLR and CRP, and low platelet count. The use of these biomarkers may better help the physician for early sepsis diagnosis and stratify patients into prognostic categories. A combination of biomarkers also appears to be a valuable practical approach to improving diagnostic accuracy.


Ab

stract - La

bo

rato

ry Resea

rch

L16

ASSOCIATION OF DENGUE WARNING SIGNS DURING FEBRILE PHASE WITH ROTATIONAL THROMBOELASTOMETRY, CORTISOL AND FERITIN

Syarifah Syahirah Syed Abas1, Noralisa Abdul Karim2, Nurasyikin Yusof3, S Fadilah Abdul Wahid2, Wan Fariza Wan Jamaludin2

1 Medical Department, Ampang Hospital, Ampang Jaya, Selangor, Malaysia; 2 Pusat Terapi Sel, Hospital Canselor Tuanku Muhriz, Cheras, Kuala Lumpur, Malaysia; 3 Hemostasis & Blood Transfusion Unit, Department of Diagnostic Laboratory Services, Hospital Canselor Tuanku Muhriz, Cheras, Kuala Lumpur, Malaysia

[email protected]

Background: Dengue mortality remains high despite monitoring against warning signs (WS). We analyzed the associations of WS at febrile phase (FP) and hemorrhage at defervescence with the levels and kinetics of rotational thromboelastometry (ROTEM), platelet count, cortisol, and ferritin.

Materials and Methods: Patients with confirmed dengue serology and WS in two centers were screened (n = 275) and 62 eligible patients were recruited prospectively over 9 months. Blood analyses for full blood count, ferritin, cortisol, coagulation profile and ROTEM parameters including INTEM (intrinsically activated pathway), EXTEM (extrinsically activated) and FIBTEM (fibrin-based thromboelastometry test) were performed during FP and defervescence.

Results: “Vomiting” was the commonest WS (62.9%), with shortened clotting time (CT) INTEM (p = 0.01). “Hematocrit increase” showed significant prolonged CT INTEM, EXTEM, and FIBTEM (p < 0.05). “Platelet decrease” showed reduced platelet function and reduced clot amplitude at 10 min (A10) and maximum clot firmness (MCF) in INTEM and EXTEM (p < 0.001). The kinetics were reduced in platelet count, CT EXTEM, and cortisol (p < 0.05) but increased in CT INTEM (p = 0.03). At FP, “vomiting”, “hematocrit increase”, and “platelet decrease” demonstrated impaired CT, clot strengths A10/MCF and platelet functions. Majority (60/62, 96.7%) had non-severe outcomes, consistent with increase in cortisol kinetics.

Discussion & Conclusion: “Vomiting”, “hematocrit increase” and “platelet decrease” at FP correlated with ROTEM. No conclusion could be made further regarding ferritin and cortisol. Larger study is required to study “hematocrit increase” with ROTEM as a potential marker for hemorrhage.


Ab

stract - La

bo

rato

ry Resea

rch

Ab

stract - La

bo

rato

ry Resea

rch

L17

CHARACTERIZATION OF RED BLOOD CELL PARAMETERS IN SOUTHEAST ASIAN OVALOCYTOSIS (SAO) AND NON-SOUTHEAST ASIAN OVALOCYTOSIS (NON-SAO) WITH OR WITHOUT THALASSAEMIA/ HAEMOGLOBINOPATHIES

Izzatul Izzanis Abd Hamid1, Mariam Mohamad2, Munirah Abdul Razak3, Ummi Mohlisi Mohd Asmawi1

1Department of Pathology, Faculty of Medicine, MARA University of Technology, Malaysia; 2Department of Public Health Medicine, MARA University of Technology, Malaysia; 3Unit of Haematology, Department of Pathology, Kuala Lumpur Hospital, Malaysia

[email protected]

Background: SAO and thalassaemia/haemoglobinopathy traits are phenotypically mild. Coinheritance of these diseases may produce a more severe form of anaemia concerning the combination of different hemolytic processes and ineffective erythropoiesis. This study aims to identify the influence of SAO with thalassaemia/haemoglobinopathies on the haematological parameters, particularly haemoglobin levels.

Materials & Methods: A cross-sectional comparative study was performed on 424 subjects investigated for thalassaemia/haemoglobinopathies using haemoglobin analysis. 212 SAO subjects were selected based on classical SAO morphology from peripheral blood film (PBF). An equal 212 non-SAO subjects were selected by the absence of SAO morphology. The demographic data, complete blood count, haemoglobin analysis, and molecular result testing were reviewed. Data analysis was performed by Chi-square test, student’s t-test, and one-way ANOVA. P-value < 0.05 was considered significant.

Results: Coinheritance of SAO with thalassaemia/haemoglobinopathy demonstrated significantly higher RBC count and lower MCV and MCH as compared to SAO without the coinheritance (5.03 x1012/L vs 4.17 x1012/L; 70.4 fL vs 81.1 fL, 23.8 pg vs 28.1 pg). Parameters comparison revealed a notable Hb, MCV, and MCH reduction, and RDW increment in SAO/β+ coinheritance.

Discussion & Conclusion: SAO with β-thalassaemia trait increases the severity of anaemia, hypochromic, and microcytosis. All suspected SAO from PBF with hypochromic and microcytosis should have further testing to exclude thalassaemia/haemoglobinopathy coinheritance as early detection and proper genetic counseling can be offered. MCHC is a potential screening tool for these coinheritances. Further studies are required.


Ab

stract - La

bo

rato

ry Resea

rch

L18

DOES OBESITY INCREASE RISK OF IRON DEFICIENCY? : A PRELIMINARY STUDY ON THE CORRELATION OF CENTRAL OBESITY, RED CELL INDICES AND IRON PARAMETERS

Farah Nur Elina Mohd Atan1, Amirah Abdul Rahman2, Yuhaniza Shafinie Kamsani3, Zalizah Khalid4, Mazapuspavina Md Yasine5, Wan Asmuni Wan Mohd Saman4

1 Institute For Medical Molecular Biotechnology; 2 Department of Biochemistry & Molecular Medicine; 3

Department of Physiology; 4 Department of Pathology; 5Primary Care Medicine Specialist Clinic, Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh Campus, Sungai Buloh, Selangor, Malaysia

[email protected]

Background: Obesity is becoming a socioeconomic burden in Malaysia with increased prevalence due to the spread of westernized diet and sedentary lifestyle. Current evidence has linked between obesity and iron deficiency (ID) and iron deficiency anaemia (IDA). These conditions lead to significant morbidity in adults and affect children’s psychological or intellectual development. We aimed to investigate the correlation between waist circumference (WC), which is an indicator of central obesity and the red cell indices (haemoglobin (Hb), mean corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH) and iron parameters (serum iron, ferritin and total iron binding capacity (TIBC)).

Materials & Methods: In this cross-sectional study, 74 subjects with BMI ≥ 25kg/m2 who fulfilled the inclusion criteria with no comorbidities were enrolled. The levels of Hb, (MCV), (MCH) and iron profile (serum ferritin, iron and TIBC) were measured. All data were analyzed using SPSS software version 26.

Results: Of all 74 overweight and obese subjects in this study, 46.0% were overweight, and 53.0% were obese. The mean age of all subjects was 34.92 (12.27) and the mean BMI was 31.20 (5.46). The mean waist circumference (WC) for male and female subjects were 90.25 (10.23) and 91.38 (11.99), respectively. The mean Hb levels for male and female subjects were 15.08 (1.08) and 12.54 (1.72), respectively (p < 0.001). Of all subjects, 55 (74.32%) of them had high WC (central obesity), with 8 (14.55%) of the subjects in this group having iron deficiency. The mean serum iron, serum ferritin and TIBC in this group were 12.82 (5.83)umol/uL, 125 (126.52) ug/L and 56.22 (8.48) umol/L, respectively. However, there was no significant correlation between high WC, red cell indices and iron parameters in this study.

Discussion & Conclusion: We observed that the Hb level, MCV, MCH and serum iron were reduced with an increase in WC. However, the correlation was not statistically significant. Therefore, further research exploring the genetic variants that may contribute to ID among this population is crucial for better understanding the mechanism of iron homeostasis and the pathophysiology of iron deficiency in obesity.


Ab

stract - La

bo

rato

ry Resea

rch

Ab

stract - La

bo

rato

ry Resea

rch

L19

GENETIC VARIANTS OF GLUCOSE-6-PHOSPHATE DEHYDROGENASE (G6PD) DEFICIENCY IN SOUTHEAST ASIAN COUNTRIES AND FUTURE DIRECTIONS OF GENOMIC MEDICINE: A REVIEW

Mohamed Afiq Hidayat Zailani1, Raja ZahratulAzma Raja Sabudin1, Hafiza Alauddin1, Siti Aishah Sulaiman2, Endom Ismail3, Ainoon Othman4

1Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre; 2UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia Medical Centre; 3Department of Biological Sciences dan Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia; 4Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia.

[email protected]

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common enzymatic X-linked disorder that is prevalent in malaria-endemic areas including Southeast Asian (SEA) countries. The spatial overlap between both diseases leads to a challenging treatment plan for a radical cure of malaria. Genomic medicine, an emerging medical discipline may serve as a potential tool for managing this overlap.

Objectives: To summarise existing knowledge on G6PD genetic variants in SEA countries and explore persisting challenges and future directions of G6PD-related genomic medicine.

Materials and Methods: Broad literature research was conducted from January 2022 to April 2022 using 3 scientific databases: Scopus, ScienceDirect, and Pubmed. The following search terms were used: “Glucose-6-phosphate dehydrogenase”, “genetic variants”, “Southeast Asia”, and “genomic medicine”. Editorials, reviews, research articles, and letters to the editors are all eligible for inclusion. A discourse analysis was followed, and a narrative review was provided on this subject.

Results: More than 14 G6PD variants of major clinical relevance were identified in the SEA countries, with G6PD Viangchan (871G>A) and G6PD Mahidol (487G > A) being the most dominant variant (35.6 – 59.6 % and 17.5 – 92 %, respectively). Five key challenges of G6PD-related genomic medicine were identified: molecular mechanism of dysfunctionality, G6PD assay reliability, community engagement disparity, genomic expertise, and healthcare accessibility.

Discussion: Genetic information gained from DNA analysis of G6PD variants helps clinicians to understand and combat malaria in G6PD-deficient individuals through effective diagnosis and population-specific therapeutic strategies. It requires collaborative efforts among society and healthcare providers. Several suggestions include empowerment of the G6PD genetic database, cultivation of genomic literacy, and development of genomic educational initiatives.

Conclusion: Due to the wide geographic distribution of G6PD variations in SEA nations, challenges to successful integration of genomic medicine into clinical care management would need to be overcome first.


Ab

stract - La

bo

rato

ry Resea

rch

L20

IMMUNOPHENOTYPING IN THE DIAGNOSIS OF ACUTE UNDIFFERENTIATED LEUKEMIA AND MIXED PHENOTYPE ACUTE LEUKEMIA

Siti Maisarah Termiti , Azizah Muhammad, Soo Chin Ng

Hematology division, Department of Pathology, Subang Jaya Medical Centre

[email protected]

Background: Acute leukemia of ambiguous lineage (ALAL) include immature hematopoietic neoplasms that show no distinct evidence of specific lineage differentiation (ie, acute undifferentiated leukemia [AUL]) as well as leukemias that express markers of more than one lineage (ie, mixed phenotype acute leukemia [MPAL]). Flow cytometry is an essential method in diagnosing AUL and MPAL. The diagnosis of AUL and MPAL depends on the specific marker used during the flow cytometry analysis. The objective of this study is to review the incidence, laboratory findings and immunophenotyping results of AUL and MPAL seen over a 3-year period.

Materials and Methods: All flowcytometry analysis of acute leukemia during period 1st January 2019 to 31 December 2021 were reviewed. The diagnosis of ALAL using WHO 2008 criteria whereby specific lineage marker of cytoplasmic MPO, cytoplasmic CD79a, cytoplasmic CD3 and CD19 are included in a primary panel of flow cytometry panel in diagnosis of AUL and MPAL.

Results: A total of 245 cases of acute leukemia was diagnosed. Acute myeloid leukemia (AML) was diagnosed in 149 (60.8%) cases, B-cell Acute Lymphoblastic Leukemia (B-ALL) was diagnosed in 84 (34.3%) cases and T-ALL was diagnosed in 9 (3.7%) cases. MPAL was diagnosed in 2 cases which accounted 0.80% of the acute leukemia and 1 case of AUL was diagnosed, accounted 0.40% of the acute leukemia.

Discussion & conclusion: Acute leukemia commonly categorize as Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL) depending on the origin of the blast lineage. AUL is a rare type of leukemia that shows no evidence of differentiation along any lineage. Clinical, immunophenotypic and genetic data is limited and the incidence, survival and optimal management is little known. In a recent review, adults AUL patients had the worst prognosis, with a median overall survival (OS) of 9 months, compared to 27 months in ALL and 13 months in AML. However, the adverse outcome was not seen in children AUL.

MPAL is generally treated with ALL directed therapy which appeared to give better results than AML directed therapy. MPAL patients with Ph chromosome will benefit from tyrosine kinase inhibitor therapy.

Due to the rarity of the cases, future multicenter studies incorporating large number of cases are needed to identify the clinical, biologic, and molecular markers for the prediction of prognosis and determine the best tailored therapy for each patient.


Ab

stract - La

bo

rato

ry Resea

rch

Ab

stract - La

bo

rato

ry Resea

rch

L21

KRÜPPEL-LIKE FACTOR 1 (KLF1) GENE MUTATION AMONG ALPHA THALASSAEMIA: RESULT OF A SINGLE REFERRAL CENTRE IN MALAYSIA

Zhi Ling, Taye1, Azlin, Ithnin1, Hafiza, Alauddin1, Nik Hafidzah, Nik Mustapha2, Munirah, Abdul Razak3

1Hospital Canselor Tuanku Muhriz, Cheras, Kuala Lumpur, Malaysia; 2Hospital Tuanku Ja’afar Seremban, Negeri Sembilan, Malaysia; 3Hospital Kuala Lumpur, Kuala Lumpur, Malaysia.

[email protected]

Background: The KLF1 gene is known as the master erythroid regulator, which play a role in regulating the expression of many erythroid genes. This gene acts as a secondary modifier, which can worsen the phenotype in α-thalassaemia. This study aimed to determine the prevalence of most commonly reported KLF1 mutation in Asian populations mutation, c.519_525dup (also known as p.Gly176fs) among the α-thalassaemia patient in a single referral centre in Negeri Sembilan, Malaysia and to describe haematological parameters in association with KLF1 mutation.

Materials and Methods: A total of 184 α-thalassaemia individuals were recruited randomly in this study. Their demographic data and haematological parameters such as Hb, RBC, MCV, MCH, MCHC, RDW, HbA2 and HbF level were obtained. High resolution melting (HRM) assay was used to screen for mutations on KLF1 exon 2-2, followed by Sanger sequencing as confirmation.

Results: From the 184 subjects, eight subjects were confirmed to have KLF1 mutation. A total of five gene mutations were identified, including one frameshift mutation, which is the most commonly reported KLF1 mutation in Asian populations, c.519_525dup, one missense and one synonymous mutation which were reported previously in the literature (c.544 T>C and 489 G>A), and two new mutations (c.446 T>C and c.469 C>A). The prevalence of c.519_525dup mutation among our subjects is 1 in 184, which is 0.54%. Our study shows that KLF1 mutation led to significantly lower MCV level in α+-thalassaemia carriers; and significantly lower Hb, HCT, MCV and MCH in -α3.7/αα subjects.

Discussion and Conclusion: The prevalence of c.519_525dup in our study population is 0.54%. This KLF1 mutation causes significantly lower MCV level in α+-thalassaemia carriers; and significantly lower Hb, HCT, MCV and MCH in -α3.7/αα subjects.

Keywords: KLF1, c.519_525dup, p.Gly176fs, α-thalassaemia


Ab

stract - La

bo

rato

ry Resea

rch

L22

MOLECULAR GENETICS OF ALPHA THALASSAEMIA IN SOUTH-EAST ASIA: A NARRATIVE REVIEW

Siti Nurrazan Binti Zulkifli 1,* , Raja Zahratul Azma Binti Raja Sabudin1 , Hafiza Binti Alauddin 1 , Noraesah Binti Mahmud 2

1Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia; 2Department of Pathology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia

[email protected]

Background: Alpha thalassaemia is the commonest inherited disorder of haemoglobin (Hb) synthesis. The red blood cells indices of alpha thalassaemia individual will usually manifests as a hallmark feature of hypochromic microcytic with or without anaemia. However, Hb analysis is incapable of giving the definite diagnosis of alpha thalssaemia carriers and require molecular analysis for a definitive diagnosis. Objective: This review paper discussed and reported narratively the molecular genetics of alpha thalassaemia in South-east Asian.

Methods: Literature search was done for three year period, from January 2019 to January 2022 with restriction to English language. The search was performed in ScienceDirect, Scopus and PubMed databases, using search terms related to alpha thalassaemia, molecular genetics and Southeast Asia.

Results: α+-thalassaemia(predominantly -α3.7), the most prevalent form in South-east Asia, showed high allele frequencies of 26% in Cambodia, 16.8% in Sabah(Malaysian Borneo) and up to 14.4% in Vietnam. Thailand have the highest allele frequencies of α0-thalassaemia, predominantly –SEA, with a prevalence of 4.46% . The non-deletional α-thalassaemia, predominantly Hb Constant Spring, is the commonest molecular abnormality in central Peninsular Malaysia with a frequency of 16.25%, while in Cambodia and Vietnam the frequencies are 8% and 14.3% respectively. However, in Java Indonesia, -α3.7 and -α4.2 were found at similar frequencies. Hb Adana was one of the commonest non-deletional α-thalassaemia mutation identified in Kelantan, north of Peninsular Malaysia.

Discussion: The multi ethnicity of Southeast-Asian populations result in diverse alpha thalassaemia molecular genetics.

Conclusion: Therefore , there is a need to regularly update the molecular genetics data. As numerous interactions of alpha genotypes with a wide range of clinical phenotypes may be encountered, develop simple and cost-effective strategies to improve the panel of detection for diagnosis, anticipating a greater difficulty in the diagnosis of alpha thalassaemia.

Keywords: Alpha thalassaemia, Molecular genetics, South-east Asian


Ab

stract - La

bo

rato

ry Resea

rch

Ab

stract - La

bo

rato

ry Resea

rch

L23

ROLE OF RUNX1 IN PLASMA CELL DIFFERENTIATION IN MULTIPLE MYELOMA PATIENTS

Ting Fang, Tang1, Won Fen, Wong1, Gin Gin, Gan2

1Department of Medical Microbiology, Faculty of Medicine, Kuala Lumpur, Malaysia; 2Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

[email protected]

Background: Multiple myeloma (MM) is the third common blood cancer of plasma cells found in Malaysia. MM is characterized by an overpopulation plasma cells in the bone marrow that results in bone lesions, and overproduction of light and heavy chains of monoclonal Ig. To date, the molecular mechanism underlying the pathogenesis of MM remains elusive. RUNX1 (Runt-related transcription factor 1) is a crucial player in the hematopoiesis process and the chromosomal translocation mutation afflicting RUNX1 is associated with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). The present study aims to elucidate the association of RUNX1 with the pathogenesis of MM and its function in the antibody-secreting plasma cells.

Materials and Methods: Plasma and B cells isolated from MM patients’ and healthy donors’ bone marrow and peripheral blood were subjected to flow cytometrical analysis and quantitative real-time polymerase chain reaction (qPCR).

Results: We observed that the percentage of CD138+ plasma cells was higher in newly diagnosed MM (NDMM) patients while higher percentage of CD19+ B cells was found in relapsed/refractory MM (RRMM) patients. Intracellular staining showed that expression level of BCL6 was high in naïve B cells population of newly diagnosed plasmacytoma patients whereas RUNX1 expression level was high in naïve B cells and plasma cells population of NDMM and newly diagnosed plasmacytoma patients. qPCR result demonstrated that the expression of RUNX1c isoform was high in NDMM stage 3 patients in comparison with NDMM patients in stage 1.

Discussion & Conclusion: Our result suggests a positive correlation of RUNX1 expression with the disease progression of MM. The findings of the present study would be helpful to improve the diagnosis and treatment of patients with MM.


Ab

stract - La

bo

rato

ry Resea

rch

L24

SIGNIFICANCE OF ABERRANT EXPRESSION OF MYELOID MARKER IN CORRELATION OF CYTOGENETIC ABNORMALITY IN PATIENT WITH B-ACUTE LYMPHOBLASTIC LEUKAEMIA

Mohd Fikri Mustapa1, Raja Zahratul Azma1, Azlin Ithnin1, Salwati Shuib1, Thatcheiany Kumariah2

1Department of Pathology, Faculty of Medicine, Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia Medical Centre, 56000 Kuala Lumpur, Malaysia2Department of Pathology, Haematology unit, Hospital Kuala Lumpur, Jalan Pahang, 50586 Kuala Lumpur, Malaysia

[email protected]

Introduction: B acute lymphoblastic leukaemia (BALL) is typically affecting children but are also encountered in adult population. BALL has a phenotypic and genotypic heterogeneity, which is of diagnostic and prognostic importance. In this study, the aberrant phenotype and cytogenetic abnormality of BALL patients were summarised and correlated.

Methods: Retrospectively, we analysed immunophenotype, cytogenetic and molecular data from 163 cases of newly diagnosed BALL from January 1st 2010 until December 31st 2020 in Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia Medical Centre (UKMMC).

Results: Out of 163 cases, 102 (62.6%) cases were CD66c positive. CD66c was the most common myeloid antigen expressed on B lymphoblasts. Ten out of 84 cases that we analysed the karyotype are hyperploid and out of these, 90% express CD66c (P=0.060). Fifteen (12%) cases displayed BCR/ABL1 gene rearrangements by FISH. Expression of CD66c was correlated with BCR/ABL1 rearrangements (P = 0.001): sensitivity 100%, specificity 43%, positive predictive value 18.6% and negative predictive value 100%. Co-expression of CD66c+ CD13+ was more frequent in BCR/ABL1+ BALL (55%) than BCR/ABL1- cases (28%) (P = 0.023). CD13 was most frequent in ETV6-RUNXI positive patient (72%) (P=0.006).

Conclusion: Positivity of CD66c with presence of the BCR/ABL1 in BALL was sensitive and correlated but not specific. It provides an early and handy tool for prediction of high-risk cases of BALL.

Keywords: BALL, aberrant myeloid, cytogenetic, ETV6-RUNX1, BCR-ABL1


Ab

stract - La

bo

rato

ry Resea

rch

Ab

stract - La

bo

rato

ry Resea

rch

L25

THE PROFILE OF CMV-SPECIFIC T CELL IMMUNE RESPONSES IN ALLOGENEIC HAEMATOPOIETIC STEM CELL TRANSPLANTATION

Norfarazieda Hassan1,2, Suzy Eldershaw2, Christine Stephens2, Jane Nunnick3, Jianmin Zuo2, Paul Moss2,3

1. Advanced Medical and Dental Institute, Universiti Sains Malaysia, 13200 Kepala Batas, Penang Malaysia ([email protected])

2. Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Vincent Drive, B15 2TT. United Kingdom

3. Centre for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, B15 2SY. United Kingdom

Background: Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is commonly used to treat a range of haematological malignancies with Human cytomegalovirus (HCMV) reactivation as one of the major risk factors. HCMV reactivation is crucial as it can lead to HCMV disease and increase mortality. In allo-HSCT, HCMV infection can initiate a very strong CD8+ and CD4+ T cell responses and indeed, these are so marked as to influence the overall profile of the peripheral T cell repertoire.

Objectives: In this study, we aim to analyse the kinetics of CD4+, CD8+, and TCRγδ T cell immune reconstitution in post allo-HSCT patients. Comparisons were made with two different control groups, allo-HSCT patients with no CMV reactivation and healthy donors.

Methods: The phenotypes of CMV-specific T cells from peripheral blood mononuclear cell (PBMC) were analysed by 10-colour flow cytometer (Gallios

TM Beckman Coulter, Inc) using HLA-Class I and HLA-Class II tetramers. Phenotype of virus-specific cells also was determined by the pattern of expression of CD57, CD38, PD-1 and CD28.

Results: Relatively unique feature of HCMV infection/reactivation has shown that magnitude of CMV-specific T cell can increase further during the period of persistent infection in post allo-HSCT.

Discussion: HCMV reactivation continually drives the expansion of CD8+ and CD4+ T cells, which bear CD57+ CD28- phenotype. Data also has shown that CMV-specific CD8+ T cells were generated earlier than CMV-specific CD4+ T cells, which implied the importance of CMV-CD8+ to control HCMV infection. Besides, this study also has provided the data on different subsets of γδ T cells, which concluded that CMV can lead to Vδ2- Vδ1+ γδ T cells expansion in allo-HSCT.

Conclusion: In overall, this study will ultimately give some insight of how to modify the clinical practice to target HCMV reactivation and improve the overall clinical outcome.


Ab

stract - La

bo

rato

ry Resea

rch

L26

VARYING PHENOTYPE PROFILE OF HAEMOGLOBIN ADANA INTERACTIONS

Gowrisankari N, Syahira Lazira O, Syahzuwan Hassan, Faidatul Syazlin Abdul Hamid, Nur Aisyah Aziz, Azian Naila MN, Ermi Neiza S, Yuslina MY, Norafiza Y, Ezalia E

Haematology Unit, Cancer Research Centre, Institute of Medical Research, National Institute of Health, Selangor.

[email protected]

Background: Hemoglobin (Hb) Adana is a highly unstable non-deletional α-thalassemia. It is caused by point mutation in codon 59 of the HBA1 or HBA2-globin gene (GGC → GAC), leading to a glycine to aspartic acid substitution. This substitution involves a glycine excess at a point of the E helix that is closely attached to a glycine residue of the B helix. This replacement significantly alters the stability and integrity of the cell’s molecule, leading to abnormal precipitates on the red cell membrane, which causes haemolysis and ineffective erythropoiesis. In this study, we aim to evaluate the difference in demographic and hematological profiles of heterozygotes and compound heterozygotes of Hb Adana.

Materials and Methods:Detection of the Hb Adana mutation was done via multiplex ARMS-PCR. The method was developed for detection of Hb Adana that affect the α2-globin gene since this variant is more common in our population. We also designed this method for detection of other common variants. The presence of common deletional alpha thalassaemias were tested using multiplex gap-PCR. These two tests were performed simultaneously as a first-line test in all cases. The second line test i.e. Sanger Sequencing, was carried out for some cases for detection of the uncommon variants.

Results: A total of 30 cases of Hb Adana were identified. These patients belonged to a variable age demographic from few months old up to 82 years of age. There were 21 (70%) females and 9 (30%) males. Majority (28, 93.3%) of them were of Malay ethnicity. There were only one (3.3%) Chinese and one (3.3%) Iban. Among these samples, 14 (46.7%) were heterozygous Hb Adana, 8 (26.7%) were compound heterozygous Hb Adana/α+-thalassemia and 8 (26.7%) were compound heterozygous Hb Adana/α-variant Hb. We excluded three paediatric patients in the haematological profile analysis, since they are considered different group. We also excluded one subject who had recent transfusion from the second group. Therefore, the haematological profiles analysis was done for 13 patients in first group and 5 patients in second group. Clinically, the first group was asymptomatic with mean+SD for Hb 13.3+1.7 g/dl. The second group presented with moderate anaemia with mean+SD for Hb 7.1+1.8 g/dl. Out of five, just one patient had occasionally transfused. The third group was transfusion-dependent since childhood, therefore its haematological profiles was not reliable for analysis. Only the MCV value was statistically different between the first and second group with mean+SD of 75.5+2.8fl and 85.7+8.0fl (p=0.01), respectively.

Discussion & Conclusion:In this study, patients with compound heterozygous Hb Adana/α+-thalassemia and compound heterozygous Hb Adana/α-variant Hb presented as Hb H phenotype while the heterozygous Hb Adana remain asymptomatic. Most of the patients with compound heterozygous Hb Adana/α+-thalassemia presented as an intermedia phenotype with only one of them had occasional blood transfusion. Patients with compound heterozygous Hb Adana/α-variant Hb had severe Hb H phenotype requiring regular blood transfusions since young age. Our findings are in concordance with other reports.

Ab

stract - C

S CR

Clin

ical


Ab

stract - La

bo

rato

ry Resea

rch

L27

VERIFICATION OF THE REFERENCE INTERVAL OF WHITE BLOOD CELL PARAMETERS OF NEUT-GI AND NEUT-RI AMONG THE LOCAL POPULATION

Ho Sook Fong1,3, Rosline Hassan1,3, Salfarina Iberahim 1,3, Mohd Zulfakar Mazlan2

1 Department of Haematology; 2Department of Anaesthesiology, School of Medical Sciences, Universiti Sains Malaysia; 3Transfusion Medicine Unit, Hospital Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia.

[email protected]

Background: The Sysmex XN-1000 is an automated haematology analyser with innovative technology which can evaluate the functional activity of neutrophils through the extended inflammatory parameters of neutrophil granularity intensity (NEUT-GI) and neutrophil reactivity intensity (NEUT-RI). The NEUT-GI is a research parameter that can provide information on the neutrophil density or complexity in response to infection. While the NEUT-RI reflects the neutrophil reactivity intensity of their metabolic activity. These two parameters are useful in the evaluation of neutrophil function in response to infection and can be potential diagnostic markers for the diagnosis of sepsis. The verification of the published reference interval of these research parameters are crucial for routine implementation and guidance in research and the future clinical use.

Objectives: The objective of this study was to verify the published reference interval of NEUT-GI and NEUT-RI for clinical and research applications in the Malaysian population.

Materials and Methods: Blood samples from 20 healthy adults were collected in BD EDTA vacutainers and full blood counts were analysed by the Sysmex XN-1000 (Sysmex, Kobe, Japan) automated haematology analyser. Sysmex XN-1000 rapidly detects activated neutrophils by using fluorescence flow cytometry of leucocyte differential based on forward and side scatter as well as internal structure such as RNA content. The NEUT-GI and NEUT-RI are rapidly available for evaluation of the functional activity of neutrophils. Data obtained were verified against the reference interval published by Cornet E et al in the year 2015.

Results: Data obtained from 20 voluntary healthy adults of both genders showed all the results were within the published reference intervals. Thus, the transference was verified. The published reference interval for NEUT-GI is 142.8-159.3 Scatter Intensity (SI); and for NEUT-RI is 39.8-51.0 Fluorescence Intensity (FI).

Discussion: The best means to establish a reference interval as recommended by the Clinical Laboratory Standard Institute (CLSI) EP28-A3c guideline is to collect samples from a sufficient number of qualified reference individuals of a minimum of 120 samples for analysis, by nonparametric means, for each partition. However, this method is costly and time consuming. Alternatively, the verification of a published reference interval can be done by a collection of a minimum of 20 samples. The verification of the published reference interval for the research parameter of NEUT-GI and NEUT-RI is needed to ensure the reliability of the published reference range for the local clinical or research purpose.

Conclusion: In conclusion, our study showed that the NEUT-GI and NEUT-RI of all samples were within the published reference intervals. Thus, the transference was verified. However, the establishment of a local reference interval rather than the adoption of a published reference interval is in a need of more accurate guidance for the clinical needs of the laboratory in the future.


Ab

stract - C

S CR

Clin

ical

cc1

A CASE REPORT OF ACQUIRED THROMBOTIC THROMBOCYTOPENIC PURPURA ASSOCIATED WITH COVID-19 INFECTION

Low Pei Ling1

Ampang Hospital, Ampang jaya, Selangor, Malaysia

[email protected]

Background :. Thrombotic angiopathy represents a dire consequence of COVID-19 infection, and such endothelial cell dysfunction and microvascular thrombosis are thought to contribute to resultant multi-organ complications.Here, we present a case report of a woman presenting with concurrent COVID-19 infection and immune thrombotic thrombocytopenic purpura (TTP).

Case report: A 33 years old lady with no known medical illness, presented with poor oral intake and vomiting for 3 days. She denied any fever or respiratory symptoms. A nasopharyngeal swabs for SARSCoV- 2 performed as outpatient turned positive. On arrival to emergency department, afebrile ,vital sign was stable with normal oxygenation, clinically appears to be pale. Lungs was clear . Full blood count taken showed severe bicytopenia , Total white cell 6.1,x 10^3 haemoglobin 3.8g/dl platelet 8 x 10^3. Urgent Full blood picture sent and showed only reactive process, true thrombocytopenia and no haemolysis. LDH and reticulocyte was normal. She was treated as immune thrombocytopenic purpura. IV methylprednisolone 1mg/kg/day was started . Patient was admitted to ward for close monitoring. Patient condition further deteriorating and haemoglobin and platelet didn’t improve with blood support and steroid. On third day admission, patient had dropped in conscious level and require intubation for airway protection. Repeated Full blood count showed total white cell 8 x10^3, Hb 5.6g/dl, Platelet 14 x 10^3. Repeated another PBF showed MAHA picture. Patient also had acute kidney injury. Urgent plain CT brain suggestive of hypodense lesion over posterior part of brain. ADAMTS13 level was sent before fresh frozen plasma was given to patient. Patient was given 8 unit fresh frozen plasma, 1 unit packed cell for 2 days subsequently. After fresh frozen plasma transfusion, patient showed improvement in conscious level and count. Patient was extubated after 2 cycle plasma exchange. Anticoagulant and empirical antibiotic was given. Fresh frozen plasma 8 unit was given for another 2 days. Total steroid was given as such iv methylprednisolone (1mg/kg/day) for 5 days then taper to 0.5mg/kg/day for 3 days . ADAMTS 13 level was 1 % with 95% inhibitor . Patient showed drastic improvement with steroid and plasma exchange. Patient count was normalised and discharge well with oral prednisolone 1mg/kg/day on day 10 admission,

Conclusion: COVID-19 infection has been associated with endotheliopathy and increased risk of VTE. There is increasing evidence that it is also associated with TTP. It is plausible that in the midst of the significant inflammation which is associated with COVID-19, these inflammatory markers that are produced by neutrophils could lead to endothelial damage and expose ADAMTS13 antigen causing antibodies formation.


Ab

stract - C

S CR

Clin

ical

Ab

stract - C

S CR

Clin

ical

CC2

A CASE REPORT OF LEPTOMENINGEAL MYELOMATOSIS AND RAPID IMPROVEMENT WITH REGIMEN CONSISTING OF DARATUMUMAB, POMALIDOMIDE, VINCRISTINE, PROCARBAZINE, AND DEXAMETHASONE

Jew Win Kuan1, Sing Ling Chai2, Pathmanathan Rajadurai3, Lee Gong Lau4, Joseph Uchang4, Sharifah Noor Akmal Syed Husain5

1Department of Medicine, Universiti Malaysia Sarawak, Kota Samarahan, Sarawak, Malaysia; 2Timberland Medical Centre, Kuching, Sarawak, Malaysia; 3Subang Jaya Medical Centre, Subang Jaya, Selangor, Malaysia; 4Borneo Medical Centre, Kuching, Sarawak, Malaysia; 5Pantai Prermier Pahtology Sdn Bhd, Kuala Lumpur, Malaysia

[email protected]

Background: Central nervous system (CNS), excluding cranium osseous or osteodural plasmacytoma, is rare in multiple myeloma (MM) (MM-CNS) compared to other haematological neoplasms. MM-CNS could be in the form of leptomeningeal myelomatosis (usually with cerebral spinal fluid (CSF) plasmatocytosis) or, rarer, brain parenchyma plasmacytoma (usually without CSF plasmacytosis). It can present at diagnosis or relapse/progression of MM, rarer in the former, and post a diagnostic and therapeutic challenge.

Case report: A 62-year-old man with underlying hypertension and anxiety disorder was diagnosed to have MM with left paravertebral plasmacytoma in March 2021, R-ISS II with high suspicion of double hit MM (aberrant nuclear p53 protein expression in ~30% of the tumour cells, positivity for FISH TP53 deletion (nuc ish(DLEUx2,TP53x1)[200]) and FISH IGH rearrangement (nuc ish(IGHx3,BCLx2)[51/200])). Local radiotherapy and lenalidomide-bortezomib-dexamethasone for 4 cycles was given bringing very good partial response (VGPR). Treatment was changed to lenalidomide maintenance when anti-tuberculosis was started in August 2021. Patient developed depressive disorder since the diagnosis of MM on top of the pre-existing anxiety disorder needing treatment.

His backache and peripheral sensory neuropathy worsened in December 2021. Paraprotein remained undetectable. Treatment from Rehabilitation Physician, Orthopaedic Surgeon, Spine Orthopaedic Surgeon, and Acupuncture Physician and later withholding of lenalidomide did not improve the symptoms. Motor weakness at right wrist and fingers appeared, which later diagnosed as systemic relapse (paraprotein 1 g/L) and progression to MM-CNS in the form of leptomeningeal myelomatosis in February 2022, as supported by multiple leptomeningeal nodular lesions in MRI brain and whole spine and CSF cytology/immunophenotyping.He decided to take traditional treatment, but symptoms worsen. He agreed for chemotherapy at the end of March 2022, when he was wheelchair/bed bound. Finger-nose test was positive. He was delirious and had visual and auditory hallucination.

A modified treatment consisting of daratumumab, pomalidomide, vincristine, procarbazine, and dexamethasone (Dara-PVPD) brought a rapid clinical improvement. He completed six cycles at the end of June 2022. Assessment post-6th cycle showed VGPR (CR with CSF and other MRI lesions except stable external capsule lesion as compared to MRI post-4th cycle). He is scheduled for thiotepa-based autologous transplantation in July 2022.

Discussion & Conclusion: There is no standard treatment for MM-CNS. Given the poor reported median overall survival of 3.5 to 6.7 months when newer drugs were not used, Dara-PVPD, was built after consideration of myeloma-effective drugs with CNS penetration (2-weekly interval: daratumumab 16mg/kg day 1, pomalidomide 4mg every Monday/Wednesday/Friday, vincristine 1.4mg/m2 (maximum 2.8mg) day 1, dexamethasone 20mg day 1-2, 10mg day 3, 4mg day 4, and 2mg day 5, procarbazine 100mg/m2 day 2-8 during odd cycle, intrathecal thiotepa 12mg and dexamethasone 4mg day 8). Intrathecal was not given as planned because patient could not be cooperative for the procedure during the first two cycles and was waiting for import permit and arrival of thiotepa. The rapid response to Dara-PVPD in this patient demonstrates potential exploration of the regimen in a further study. Incorporation of intrathecal thiotepa into the regimen would likely increase the efficacy.


Ab

stract - C

S CR

Clin

ical

CC3

ACUTE PROMYELOCYTIC LEUKEMIA DURING PREGNANCY WITH DIFFERENTIATION SYNDROME

Sook Yee Ho, Kirubamoorthy Kamini²

¹Hospital Raja Permaisuri Bainun, Ipoh, Perak, Malaysia

[email protected]

Background: It is challenging in managing acute promyelocytic leukemia (APL) during pregnancy in view the possible teratogenicity to fetus and adverse maternal outcome.

Case Report: A 39-year-old Malay lady diagnosed with acute promyelocytic leukemia (APL) at 24-weeks of gestation with presentation of pancytopenia and easy bruising. She was treated with all-trans-retinoic acid (ATRA), Idarubicin and dexamethasone. She developed differentiation syndrome on the 11th day of ATRA and managed with dexamethasone. She delivered a healthy baby boy with no deformities at 36 weeks of gestation via spontaneous vaginal delivery complicated with primary postpartum haemorrhage secondary to uterine atony which given medical therapy and blood transfusion. After the delivery, she completed two courses of Idarubicin for consolidation and third course was stopped due to neutropenic sepsis. She has completed maintenance therapy for 18 months. At the time of this report, she is in remission and her child is doing well.

Discussion & Conclusion: There are several considerations in giving ATRA and Idarubicin in induction for pregnant patients in view of the potential teratogenecity risk to the fetus as well as the risk of differentiation syndrome to the mother. Discussion and explanation to the mother regarding such risks are important and fetal surveillance scans are required throughout the pregnancy. In this case, the patient had differentiation syndrome one week after started on ATRA with symptoms of pleuritic chest pain, dyspnea and desaturation. She was given diuretics, dexamethasone and supplementary oxygen and clinical resolution was seen after three days. Differentiation syndrome is one of the causes of induction death in APL and the mortality is as high as 9%. Hence it is important to have a high clinical suspicion when patient developing the symptoms in order to institute treatment promptly. Pregnancy is a prothrombotic state hence it is challenging to manage patient of APL during pregnancy. Although APL is commonly known for bleeding complications, thrombosis is also not uncommon with approximately of 5-20% risk of thrombotic events during induction therapy. The mechanism of bleeding is due to hyperfibrinolysis, which could be possibly explained by the expression of annexin II by promyeloblasts that results in abnormal activation of plasmin and degradation of fibrin and fibrinogen. On the other hand, the overexpression of various cytokines including interleukin -1β, interleukin -6 and tumour necrosis factor –α, augments the tissue factor and plasminogen activator inhibitor -1 activities. The balance of managing coagulopathy and maintaining reasonable platelet count more than 30 x 10 ^9/L with platelet, cryoprecipitate or fibrinogen transfusion in the context of thromboembolic risk during pregnancy requires discrete clinical judgement. The role of prophylactic heparin in managing pregnant patients with APL is unclear as little data to guide the clinicians. Strategies to reduce the bleeding and thrombotic risk in this group of patients remains the clinical challenge for the clinicians.


Ab

stract - C

S CR

Clin

ical

Ab

stract - C

S CR

Clin

ical

CC4

AN UNUSUAL CAUSE OF SPURIOUS HYPERLEUCOCYTOSIS

Jin Teng Wu1,4, TG Wong2, Anisah A3 Nor Ainiza M3,Wan Nazirah WAB3, Ahmad Kashfi HJ AR4, Siti Nor Suhailah S1, Nurfalahin A1 ,Muhammad Faqihuddin 1, Aslinda Kalthom A1, Afifi Syamil AR1, Che Ku Hafizah CKA1

1Hospital Setiu2Haematology Hosp Ampang3Pathology HSNZ 4 Infectious disease unit, Medical HSNZ

[email protected], [email protected]

Background: Malaria infection is a potentially lethal but treatable infectious disease. We reported an unusual hyperleukocytosis as initial presentation for severe Malaria.

Case Report: A 64-year-old inactive gentleman with underlying hypertension presented with intermittent fever, lethargy and reduced oral intake for 5 days. Upon arrival, he was lethargic, jaundiced, dehydrated, hypoperfused and mildly tachypnea. Higher mental function was preserved. He was afebrile, blood pressure 82/56mmHg, heart rate 119bpm, respiratory rate 40bpm, saturation 64% under room air, capillary blood glucose 5.0mmol/L. There was splenomegaly (3cm palpable spleen), no lymphadenopathy nor hepatomegaly. Blood gas pH 7.15, HCO3 unrecordable, lactate 13.1. FBC: haemoglobin 14.4g/dL, platelet 38 x 103/uL, WBC 292 x 103/uL with predominantly neutrophil (286.6 x 103). Coagulation profiles were normal. Urea47mmol/L, creatinine 648mmol/L, sodium 126mmol/L, potassium 4.2mmol/L, uric acid 746mmol/L, calcium 1.77mmol/L, phosphate 2.76mmol/L, total bilirubin 60umol/L (direct bilirubin 30umol/L), ALT 74U/L, AST 113U/L, CRP 185.2mg/L, LDH 1029U/L, CK 1172U/L. Leptospirosis rapid tests were negative. Chest radiograph was normal. Urine test revealed hematuria (3+). Initial impressions of highly suspicious acute leukaemia with hyperleukocytosis, spontaneous tumour lysis and occult sepsis were made. However prompt family conferences decided for conservative management. Repeated FBC haemoglobin 10.3g/dL, platelet 64 x 103/uL, WBC 263 x 103/uL with predominantly neutrophil (241.7 x 103). Urgent full blood picture was reported as inaccurate white cell count, presence of many malaria parasites at various stages of maturation, no blast cells or platelet clumping. BFMP returned as plasmodium knowlesi parasitemia: 166,400/272,000 per uL blood, this was confirmed later with Malaria PCR test. Antimalaria had been given promptly, however he deteriorated rapidly and demised within 24 hours after admission.

Discussion & Conclusion: Malaria is an infectious disease caused by protozoan parasites of the genus Plasmodium. The early symptoms of infection are non-specific. Classical manifestation of malaria is paroxysm: cyclical chills and rigor followed by high grade temperature. Diagnoses are mainly driven by clinical suspicion and confirmed with a parasitological test: BFMP or PCR.

We found hyperleukocytosis in repeated tested samples, using haematology analyzer SYSMEX XN 330. However manual FBP showed normal WBC analysis (neutrophil 79%, lymphocytes 17%, monocytes 4%). This pseudo-hyperleukocytosis phenomenon in malaria infection has never been illustrated before. We postulated that samples were poorly responded to the cell lysis buffer thus our haematology analyzer had mistakenly taken malaria infected RBC as WBC. However, we were unable to get more blood samples for further testing. We had revised our diagnosis and acted immediately thereafter. He somehow did not respond to our treatment.In summary, we illustrated a case of severe malaria with subtle symptoms but unusual hyperleukocytosis. Both conditions carry high mortality rates. High index clinical suspicion with early intervention are the keys to prevent mortality or morbidity. Collaboration with lab technicians, hematopathologists, haematologists are important when dealing with extremely abnormal blood results.


Ab

stract - C

S CR

Clin

ical

CC5

AUTOLOGOUS STEM CELL TRANSPLANTATION IN YOUNG ADULT WITH SOFT TISSUE AND BONE SARCOMA – SINGLE CENTRE EXPERIENCE

Mohd Yazid Zamri, Ping Chong Bee, Chin Sum Cheong, Fui Min Edmund Chin, Shasha Khairullah, Chee Chiat Liong, Gin Gin Gan

Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

Background: High dose Chemotherapy ( HDCT ) and Autologous Stem cell transplantation ( ASCT) is well established as an consolidative treatment in haematological malignancies such as Hodgkin’s and non-Hodgkin’s lymphoma. HDCT/ASCT is also used in solid tumors but it is mostly indicated as a salvage rather than a consolidative treatment for relapsed or refractory diseases. It is proven to improve the prognosis in germ cell tumor. However, the effectiveness of HDCT/ASCT in other types of solid tumors such as soft tissue or bone sarcoma is less known especially in our country.

Objective: To describe the outcome of HDCT/ASCT for solid tumor in University Malaya Medical Centre.

Methods: All patients with solid tumors who underwent HDCT/ASCT are included in the analysis. The data is retrieved retrospectively from our transplant registry.

Results: There is a total of 7 patients, 3 with Ewing sarcoma followed by 2 cases of osteosarcoma and 2 cases of Germ cell tumor. There are 5 males and 2 females. The median age is 22 years old (range from 15 to 28 years old). The overall survival is 42.8% (3 out 7 patients, 2 Ewing’s sarcoma and 1 osteosarcoma) and disease free survival is 28.5%. (2 out 7 patients) There is no transplant related mortality. Chemo-sensitive is the determinant of survival, 2 survivors achieved complete remission and 1 survivor had partial remission before underwent HDCT/ASCT. All mortality is due to disease progression. Median duration of survival of patients was 25 months, with longest duration of 137 months after HDCT/ ASCT. All patient received at least up to second line chemotherapy except 1 patient with refractory germ cell tumor. Majority of patients received combination of chemotherapy with adjunctive therapy including surgical resection and radiotherapy prior to HDCT/ASCT.

Discussion: HDCT/ASCT as a consolidative therapy is potentially curative for soft tissue and bone sarcoma in our series. Chemo-sensitive is the strong predictor for excellent outcome. Chemo-sensitive relapsed diseases should be referred early for HDCT/ASCT.


Ab

stract - C

S CR

Clin

ical

Ab

stract - C

S CR

Clin

ical

CC6

CASE REPORT: USE OF ARSENIC TRIOXIDE PLUS MANNITOL IN AN ACUTE PROMYELOCYTIC LEUKEMIA PATIENT WITH CENTRAL NERVOUS SYSTEM RELAPSE

Tiong Chiong Seng1,3, Ko Ching Tiong1, Leong Tze Shin2, Tang Andy Sing Ong2, Lee Grace Wan Chieng, Chew Lee Ping2

1Department of Pharmacy, Sarawak General Hospital, Sarawak, Malaysia;2Department of Internal Medicine, Hematology Unit, Sarawak General Hospital, Sarawak, Malaysia.

[email protected]

Background: Central nervous system (CNS) relapse occurs rarely in acute promyelocytic leukemia (APML). Patients with CNS APML have poor prognosis. Standard treatment of APML often includes arsenic trioxide (ATO). However, ATO have poor permeability to cross blood brain barrier (BBB) due to its high water-solubility. Several studies had purposed to utilize mannitol 20% to improve the BBB permeability of ATO and the results are promising.

Case study: We had a 24-year-old male, diagnosed as APML. He was treated with standard APML protocol (idarubicin and ATRA) as induction followed by three courses of consolidation using idarubicin and maintenance therapy for 11 months. Investigations during maintenance revealed that he had molecular relapse of APML with morphological remission with CNS infiltration. Treatment was started with ATO plus ATRA, and later changed to ATO with mannitol and intrathecal treatment. Arsenic trioxide was diluted with 125mL of mannitol 25% in a total of 500mL NS. For the administration, 125mL of mannitol 20% was given as intravenous bolus over 10 minutes using chamber, followed by arsenic trioxide plus mannitol administered as intravenous infusion over 4 hours. Intrathecal therapy was given via Ommaya shunt. The patient completed chemotherapy for total of 60 days and went for autologous stem cell transplant.

Discussion/Conclusion: Mannitol facilitates ATO to cross BBB by reversibly widening the intracellular gaps of BBB. This allows more arsenic trioxide to cross into CNS and act on the leukemic cells. Arsenic trioxide plus mannitol 20% is a feasible non-invasive option for treatment of APML with CNS infiltration with minimal side effects.


Ab

stract - C

S CR

Clin

ical

CC7

FACTOR VII DEFICIENCY: A RARE DISEASE WITH EVEN “RARER” TREATMENT

Andy Sing Ong Tang1, Ching Tiong Ko1, Tze Shin Leong1, Betty Sue Ho Lee2, Lee Ping Chew1

1Haematology Unit, Department of Medicine, Sarawak General Hospital, Sarawak, Malaysia;2Haemato-oncology Unit, Department of Paediatrics, Sarawak General Hospital, Sarawak, Malaysia

[email protected]

Background: Factor VII (FVII) deficiency, a rare autosomal recessive bleeding disorder, is characterized by a deficiency or reduced activity of FVII. While plasma-derived FVII concentrate is unavailable in Malaysia, recombinant activated FVII (rFVIIa) can be expensive and limited in stock. We aim to report two cases of FVII deficiency with severe bleeding phenotype, treated using 4-factor prothrombin complex concentrate (PCC).

Case Series:Case (1) A 15-year-old Malay boy, product of non-consanguineous marriage, was diagnosed with FVII deficiency (<1%) when he presented with intraventricular bleed at 3-month-old. Despite 15ml/kg weekly fresh-frozen plasma (FFP) prophylaxis, he had monthly joint and mucosal bleed since 3-year-old. Due to an anaphylactic episode to FFP, rFVIIa was used until 2017 when it was stopped due to economic reasons. He was then started on 4-factor PCC at 24units/kg twice-weekly, with no breakthrough bleeding or thrombotic events since then. He is currently attending special school with independent activity of daily living (ADL).

Case (2) A 32-year-old Iban boy, from non-consanguineous parents, presented with intracranial bleed at 6-month-old when a diagnosis of FVII deficiency (<1%) was made. FFP was administered for recurrent haemarthrosis and muscular bleeds, followed by 10ml/kg twice-weekly prophylaxis. He was then put on rFVIIa prophylaxis between 2014 and to early 2021, but again was stopped due to economic reasons. Subsequently he was started on 4-factor PCC 1000IU twice-weekly (weight 87 kg) prophylaxis with no breakthrough bleeding or thrombotic events. He is employed full-time now with good quality-of-life.

Discussion & Conclusion: We reported two cases of FVII deficiency treated successfully with 4-factor PCC with no adverse events and safety concerns. An average saving of RM25,000-RM40,000/year is estimated comparing equivalent FVII dosage between rFVIIa and PCC prophylaxis.


Ab

stract - C

S CR

Clin

ical

Ab

stract - C

S CR

Clin

ical

CC8

FORGOTTEN BUT NOT DISAPPEARED: ERYTHROPOIESIS STIMULATING AGENT INDUCED PURE RED CELL APLASIA

Jerome Tan Tsen Chuen1, Andy Tang Sing Ong1, Yip Kam Hoo1, Ganesh Kasinathan1, Norazinizah Ahmad Mizwan2, Kong Su Shan3

1 Department of Haematology, Hospital Ampang Selangor;2Nephrology Unit, Hospital Ampang Selangor;3Department of Pharmacy, Hospital Ampang Selangor

[email protected]

Background: Erythropoiesis Stimulating Agent (ESA) induced pure red cell aplasia (PRCA) is caused by the development of neutralizing antibodies against exogenous ESA, cross-reacting with endogenous erythropoietin resulting in PRCA. Introduction of recombinant human ESA in the late 1980s for chronic kidney disease patients resulted in increased reports of PRCA in the late 1990s. However, changes in the manufacturing and storage of ESAs have reduced the incidence of this potential serious adverse effect.

Case Report: Here we report a case of a 45 years old gentleman who was initially referred to the Nephrology Unit in 2019 for chronic kidney disease (CKD) Stage 4 with an estimated EGFR of 24ml/min. He is a known diabetic and hypertensive. Within a year he progressed to CKD stage 5 with EGFR of 12ml/min. At that time his Hb was 9.5g/dL without any ESA support. He was subsequently counselled for CAPD and in Jan 2021 his Hb deteriorated to 6.6g/dL. OGDS and colonoscopy did not show any evidence of overt gastrointestinal bleeding. He was then commenced on s/c Epoeitin α 2000 IU 2x a week from Aug 2021 till Nov 2021. In Dec 2021, his Hb further deteriorated to 3.0g/dL despite Epoeitin α support. Repeated scopes did not reveal any evidence of gastrointestinal bleeding. His ESA was then switched to s/c Epoetin β 4000 IU 3x a week. His serum erythropoietin (EPO) level in Jan 2022 was undetected (normal range 3.22-31.9 mIU/mL). He continued to receive packed cell transfusions 2-3 weekly with pre-transfusion Hb ranging from 3.5 - 7.5g/dL. A repeated serum EPO level after 3 months of Epoetin β therapy was performed and level was still undetected. Subsequently a bone marrow examination was done and the results were consistent with the diagnosis of pure red cell aplasia. The patient was not on any medications known to cause marrow aplasia but had detected IgG antibodies to B-19 parvovirus and EBV. Further Epoetin β therapy was ceased. His serum was sent for anti-EPO ELISA assay to a reference laboratory in Germany courtesy of Roche (Malaysia) and the result confirms the presence of anti-EPO antibody with a titre of 7648.

Discussion & Conclusion: ESA induced PRCA is a rare complication of ESA therapy and is reportedly more common in subcutaneous compared to intravenous administration. Host cell contamination, protein modifications in the manufacturing or leaching of compounds from prefilled syringes of rHuEPO have previously been implicated. With the increasing use of ESA with intravenous iron as therapy for iron deficiency anaemia, clinicians need to be aware of this potential rare serious adverse event. Currently there is limited access to EPO antibody testing which hinders a confirmatory diagnosis. Post marketing surveillance for PRCA needs to be continued especially with the differing manufacturing practices of rHuEPO of many generics.


Ab

stract - C

S CR

Clin

ical

CC9

HAEMOPHAGOCYTIC SYNDROME SECONDARY TO DISSEMINATED TUBERCULOSIS MASQUERADING AS DIFFERENTIATION SYNDROME IN A CASE OF APML POST ATRA-IDARUBICIN INDUCTION

Zhao Sheng Bong1, Kam Hoo Yip1, Soo Min Lim1

1 Department of Haematology, Hospital Sultanah Aminah, Johor Bahru, Johor, Malaysia.

[email protected]

Background: Acute Promyelocytic Leukaemia (APML) is notorious for having a stormy clinical course at diagnosis and induction. Haemophagocytic syndrome has been reported in cases of APML and the diagnosis and treatment can be challenging.

Case Report: A 30-year-old man presented with a 4-day history of fever and bleeding tendencies. A full blood count revealed pancytopenia (Hb 9.9g/dL, TWC 3.4, Plt 8) and his peripheral blood film demonstrated the presence of 84% abnormal promyelocytes, faggot cells and absence of neutrophils. ATRA was started immediately with blood product support and the diagnosis of APML was later confirmed by the presence of PML-RARA transcript in rt-PCR assay from his bone marrow studies. A rising TWC count to a high of 59.9 post ATRA prompted the use of oral dexamethasone 8mg BD for 12 days as prophylaxis against differentiation syndrome while Idarubicin induction was initiated at day 4 (D4) post ATRA. The patient had persistent fever which failed to abate with a battery of antibacterial and antifungal agents with serial negative blood cultures. Serial chest x-rays showed a worsening bilateral lung field heterogenous opacity and a CECT TAP reported the presence of bilateral ground glass appearance in the lungs with necrotic left perihilar node. Multiple sputum AFB was negative and a bronchoscopy with bronchoalveolar lavage also returned negative for AFB smear, GeneXpert MTB PCR and MTB culture. An empirical treatment for Pneumocystis jirovecii pneumonia (PJP) with high dose Bactrim and Prednisolone seemed to resolve the fever with clinical improvement of the patient and he was discharged 4 days later at D39 with Hb 8.4, TWC 4.9, ANC 3.0, Plt 115. He unfortunately turned for the worse a week later (D46) with fever, breathlessness, fluid retention, transaminitis (ALT 170, AST 168), AKI (Creat 136, Urea 7.9) and worsening cytopenia (Hb 7.5, TWC 1.8, ANC 1.7, Plt 36). CXR also showed bilateral pulmonary infiltrate. Bactrim was withdrawn and IV Dexamethasone was started for the treatment of late onset differentiation syndrome along with antibiotics for sepsis. His condition did not improve. A spiking temperature with worsening cell counts, rising bilirubin (90umol/L), hepatomegaly, and worsening creatinine raised the suspicion of malignancy associated haemophagocytic syndrome (MAHS). This was supported by a ferritin of >100,000ug/L, triglyceride of 4.2mmol/L, and a bone marrow aspirate showing haemophagocytic activity with no residual abnormal promyelocytes giving a HScore of 292 (>99% probability). The patient by then had been intubated and ventilated with worsening multiorgan failure and was on inotropic support. A dose of Etoposide at 75mg/m2 was given with dexamethasone but he continued to deteriorate and passed away at D58 from pulmonary haemorrhage. It was only after his death that his trephine biopsy was reported to have acid-fast bacilli seen which was later confirmed with a positive MTB culture.

Discussion & Conclusion: Secondary haemophagocytic syndrome can occur with APML and may also happen concurrently with differentiation syndrome as have been reported in some case studies. Tuberculosis as a cause should be looked for actively in our locality and more so in an immunosuppressed patient.


Ab

stract - C

S CR

Clin

ical

Ab

stract - C

S CR

Clin

ical

CC10

HEPATIC LYMPHOMA CAMOUFLAGE AS LIVER ABSCESS

Guang Yong Chong1, Sivakumar Palaniappan1, Nor Rafeah Tumian1

1 Department of Medicine, Hospital Canselor Tuanku Muhriz Universiti Kebangsaan Malaysia (HCTM UKM), Kuala Lumpur, Malaysia

[email protected]

Background: Clinical suspicious of hepatic lymphoma in liver abscess patient is diagnostic importance, as it affects the outcome of treatment and prognosis.

Case series Case (1) A 23-year-old gentleman with previous history of immune thrombocytopenia presented with intermittent fever, lethargy, loss of appetite and weight for 4 months. Liver function test and lactate dehydrogenase within normal range. Abdomen ultrasound shown multiple liver and splenic abscesses with intraabdominal lymphadenopathies. He was empirically treated for extrapulmonary tuberculosis in view of non-resolved fever however subsequent CT imaging follow up shown persistent lesions. Liver biopsy was done and consistent with Hodgkin Lymphoma. He received 6 cycles of ABVD and current disease status in complete remission.

Case (2) A 40-year-old gentleman with newly diagnosed retroviral disease presented with epigastric and right hypochondrium pain for 3 months associated with abdominal distension and jaundice. Lab investigations noted hyperbilirubinemia and transaminitis. Ultrasound abdomen shown multiple liver and splenic lesions suggestive of metastatic lesion or abscesses. Peritoneal fluid flowcytometry shown lymphomatous infiltration of B-cell lymphoma and liver biopsy consistent with diffuse large B-cell lymphoma. He was given 6 cycles of R-CHOP chemotherapy and end of treatment PET-CT in complete remission.

Case (3) A 28-year-old gentleman with underlying retroviral disease on antiretroviral therapy with stable CD4 count and undetectable viral load. He presented with systemic symptoms for 3 months. PET-CT shown widespread metastatic disease with liver and spleen involvement but no obvious primary lesion. Liver biopsy taken as it showed lesion with highest uptake at segment VII. Histopathology reported as Hodgkin Lymphoma and he is currently on ABVD chemotherapy.

Discussion & Conclusion: Hepatic involvement with lymphoma is common and can be divided into primary or secondary involvement. Most common hepatic lymphoma is Non-Hodgkin Lymphoma. Risk factors for developing hepatic lymphoma are HIV/AIDS, hepatitis C infection and immunosuppression. Right upper quadrant pain, hepatomegaly, jaundice, and hepatic failure are the main presenting features. Imaging modalities are helpful in defining a hypoechoic mass on ultrasonography and hypoattenuating lesion on computed tomography scan. Clinical recognition of these lesions at the time of initial staging is difficult because hepatic infiltration by lymphoma is usually diffuse rather than focal. Biopsy of the lesion is the next step in diagnostic chain if clinical suspicious arise and help to avoid confusion with hepatocellular carcinoma, metastasis, or abscess. Chemotherapy is the mainstay of treatment with complete remission can be achieved in more than 80% of the patients.


Ab

stract - C

S CR

Clin

ical

CC11

HEPATOSPLENIC T-CELL LYMPHOMA : A RARE BUT AGGRESSIVE DISEASE

Tham Yea Bing1, Sharifah Shahnaz Syed Abd Kadir1

1Hospital Ampang, Ampang Jaya, Selangor, Malaysia

[email protected]

Background: Hepatosplenic T-cell lymphoma(HSTCL) is rare T cell neoplasm with a rapidly progressive clinical course and poor outcome due to its refractoriness to conventional chemotherapy. We reported 5 cases of HSCTL treated in Hospital Ampang from 2010 to 2020.

Case ReportCase (1) 14-year-old girl, presented with constitutional symptoms for 1 week. There were hepatomegaly(25cm), splenomegaly(24cm) and pancytopenia with haemoglobin 6g/dL, white blood cell(WBC) 3.6x109/L(absolute neutrophil count(ANC) 1.8) and platelet 23x109/L. Bone marrow aspiration and trephine biopsy(BMAT) showed HSTCL. She was started on German Multicenter Acute Lymphoblastic Leukemia(GMALL) induction chemotherapy(containing vincristine, daunorubicin, dexamethasone, L-asparaginase with intrathecal methotrexate). However, her condition deteriorated and passed away due to neutropenic sepsis.

Case (2) 40-year-old lady, underlying Diabetes Mellitus and Hypertension, presented with abdominal distension and constitutional symptoms for 2 weeks. There were hepatomegaly(18cm), splenomegaly(30cm) and pancytopenia with haemoglobin 5g/dL, WBC 1.6x109/L(ANC 0.9) and platelet 24x109/L. BMAT showed HSTCL. She was given MACOP-B(methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisolone, bleomycin). She developed neutropenic sepsis with Pseudomonas aeruginosa and Staphylococcus aerus bacteraemia and succumbed to death.

Case (3) 55-year-old gentleman, underlying hypertension, presented with constitutional symptoms for 1 month. There were hepatomegaly(18cm), splenomegaly(18cm) and pancytopenia with haemoglobin 8g/dL, WBC 2.5x109/L(ANC 2.1), and platelet 8x109/L. BMAT showed HSTCL. He was given 2 cycles of Half-CHOP(cyclophosphamide, doxorubicin, vincristine, prednisolone) and 3 cycles of CHOEP(cyclophosphamide, doxorubicin, vincristine, etoposide, prednisolone). However, his disease was refractory to chemotherapy with persistent pancytopenia. Patient was not keen for salvage chemotherapy and passed away due to progression of disease.

Case (4) 41-year-old gentleman presented with constitutional symptoms for 1 month. There was hepatomegaly(22cm), splenomegaly(16cm) and pancytopenia with haemoglobin 8g/dL, WBC 1.2x109/L(ANC 0.6) and platelet 60x109/L. BMAT showed HSTCL. He completed 1 cycle of CHOP and 3 cycles of hyperCVAD-A(cyclophosphamide, vincristine, doxorubicin, dexamethasone with intrathecal methotrexate and cytarabine) alternating with 2 cycles of hyperCVAD-B(methotrexate, cytarabine, methylprednisolone with intrathecal methotrexate and cytarabine). He achieved remission but did not agree for allogeneic stem cell transplant(AlloSCT). His disease relapsed 6 months after completion of chemotherapy. He was not keen for salvage chemotherapy. Subsequently, he was lost to follow up.

Case (5) 65-year-old lady, underlying Meningioma in remission post-radiotherapy, hypertension and dyslipidaemia, presented with reduced effort tolerance for 3 months. There were hepatomegaly(22cm), splenomegaly(25cm) and pancytopenia with haemoglobin 7g/dL, WBC 1.7x109/L(ANC 0.9) and platelet 74x109/L. BMAT and splenic biopsy showed HSTCL. She completed 2 cycles of ICE(ifosfamide, carboplatin) and 4 cycles of DHAP(dexamethasone, cytarabine, cisplatin). She achieved remission. She underwent matched unrelated donor AlloSCT. 3 months post-AlloSCT, she had Cytomegalovirus(CMV) reactivation with CMV meningoencephalitis and Candida pneumonia. She passed away on Day+130 post-AlloSCT due to infectious complications from AlloSCT.

Discussion / ConclusionThe clinical presentation in our patients is similar to that described in literature, with hepatosplenomegaly, constitutional symptoms, pancytopenia and infiltration of bone marrow. There is no standard treatment regime for HSTCL. Generally, there is poor outcome of our patients with chemotherapy alone. In conclusion, patients with this rare, aggressive lymphoma need to be managed aggressively with early consideration of AlloSCT.


Ab

stract - C

S CR

Clin

ical

Ab

stract - C

S CR

Clin

ical

CC12

HYPEREOSINOPHILIC SYNDROME WITH CRADIAC INVOLVEMENT: A CASE REPORT

Jeevakanthi Rajendran, Gan Ee Leng and Toh See Guan

Haematology Unit, Departnment of Medicine,Hospital Tuanku Jaafar, Seremban (HTJS)

Background : Hypereosinophilic Syndrome (HES) is define as eosinophil count of more than 1.5 x 10^9 /l or greater persisting for at least 6 months, for which no underlying cause can be found and which is associated with signs of organ involvement and dysfunction. The causes are divided into three main categories secondary (reactive), primary and idiopathic. HES predominantly affects males, with an estimated male-to-female ratio ranging up to 9:1 (Weller & Bubley, 1994). This is largely explained by the fact that the FIP1L1-PDGFRA fusion gene occurs almost exclusively in males.

Case Report : Here, we describe a rare cardiac presentation of HES. Mr.V is a 37 years old Indian gentleman who has no known medical illness previously. He presented initially to private hospital complaining of palpitations and chest discomfort. He was treated for fast atrial fibrillation, in which the rhythm reverted succesfully with amiodarone. His initial ECHO dated 21/5/2021 showed mid-range heart failure with moderate pericardial effusion, largest pool at lateral left ventricle measuring 2.0cm. Interestingly, his full blood count revealed high eosinophils count of 3.24 x 10^3/ul. Clinically, he was not anemic, no purpuric rashes and no splenomegaly noted. There were no history of angioedema in the past as well. He was then started on Tab Hydroxyurea 1g OD and Tab Prednisolone 15mg OD in view of persistent eosinophilia and referred to Hematology Unit of HTJS subsequently. The full blood picture shows evidence of leukocytosis with eosinophilia and mild basophilia. No blast or abnormal lymphoid cells. Fluorescence in situ hybridization (FISH) for FIPILI-PDGFRA rearrangement was sent and was not detected. His bone marrow aspirate and trephine biopsy shows eosinophilia with no evidence of acute leukemia or marrow infiltration. Patient has been well treated with Tab Hydroxyurea and after 1 year of treatment, his eosinophilic count has been normalized to 0.45 x 10^3/ul. He has not developed any atrial fibrillation after initiation of treatment for eosinophilia. The ECHO post treatment at 6 months revealed normal (preserved) ejection fraction and completely resolved pericardial effusion.

Conclusion & Discussion : In short, this case highlights the importance of being able to recognize eosinophilia as one of the cause of cardiac dysfunction. The basic pathology of HES is the infiltration of eosinophils in organ tissues. Eosinophil cationic proteins are enzymes released by eosinophils that cause tissue damage and promote fibrosis and thrombosis. The cardiac manifestation of HES include pericarditis, myocarditis, cardiac arrhythmias, cardiac failure, ventricular thrombus, endomyocardial fibrosis and restrictive cardiomyopathy. Early intervention/normalization of eosinophilia will help to prevent further cardiac damage and potentially reverse cardiac morbidity as well as mortality, as what happened in this case.


Ab

stract - C

S CR

Clin

ical

CC13

IT IS NOT ALWAYS THALASSEMIA - A CASE REPORT OF AUTOIMMUNE HAEMOLYTIC ANAEMIA IN A PATIENT WITH HAEMOGLOBIN LEPORE

Swee Looi Tan1 , CH Goh2

Hospital Tengku Ampuan Rahimah Klang, Selangor, Malaysia

[email protected]

Background: Hb Lepore is a structurally abnormal haemoglobin resulting from fusion of the δ and β globin gene. A rare form of Thalassemia in Malaysia, it was first discovered in 1958 with 3 variants i.e. Hb Lepore Washington Boston, Hb Lepore Hollandia and Hb Lepore Baltimore. Autoimmune hemolytic anaemia is a form of decompensated acquired hemolysis caused by the host immune system acting against its own red cell antigens. We wish to report a female patient with Hb Lepore who was later diagnosed with autoimmune haemolytic anaemia.

Case Report: A 30 year-old lady with Hb Lepore Hollandia first presented at age 13 with history of anaemia and jaundice for 1 year. Family history revealed that she is the second child of a non-consanguineous union. Her elder brother is a known case of thalassaemia major and is transfusion dependent. Her three younger siblings were asymptomatic with no transfusion history. Clinical examination revealed pallor and jaundice with hepatosplenomegaly.

Baseline FBC showed microcytic hypochromic anaemia. Hb electrophoresis showed Hb F= 90.1% and Hb A2=13.5%. No H inclusion detected. This was suggestive of either homozygosity with variant Hb or double heterozygosity for variant Hb and β-thalassaemia.

2005-2012: Patient was on regular follow-up, with nil blood transfusion. However there was a brief default from treatment until May 2010; when she was admitted for symptomatic anaemia, which was attributed to iron deficiency. No blood was transfused.

2012-2017: Patient continued to have persistent mildly symptomatic anaemia. She eventually required irregular blood transfusion of 1-3 packed red cells monthly. Her ferritin level ranged from 500-700 μg/l. Homozygous state of Hb Lepore Hollandia was confirmed via DNA analysis in 2014.

From November 2017, we noted a sudden increase in her transfusion requirement, up to biweekly. Pretransfusion Hb had worsened to 5-6g%. In addition to lethargy, she complained of abdominal pains and worsening jaundice. She was admitted for further investigation and subsequently referred to Surgery for splenectomy. However looking back at past records, we noted a positive ANA screen in 2011. Hence, the splenectomy was delayed to consider an autoimmune cause for the patient’s condition. Repeated screening was done and confirmed significant ANA and dsDNA titres.

A Direct Coombs test performed was positive. Meanwhile, the patient was promptly commenced on oral Prednisolone which was tapered over a period of 6 months to maintenance. She responded well. Her Hb trend improved tremendously and maintained at a range of 9-10g%.

Splenectomy was called off and after seeking rheumatology opinion, she was eventually diagnosed with systemic lupus erythematosus with AIHA. Blood transfusion became only as per required needs.

Discussion & Conclusion: This report highlights the importance of considering other diagnoses for anaemia in a patient with Thalassaemia. The patient’s Direct Coombs test was found to be positive just in time to avoid splenectomy and its associated life-threatening complications including the risk of acquiring opportunistic infections. When managing Thalassemia patients, we must bear in mind that they are vulnerable to other forms of diseases that afflict humankind.


Ab

stract - C

S CR

Clin

ical

Ab

stract - C

S CR

Clin

ical

CC14

CASE REPORT : LONGITUDINAL EXTENSIVE TRANVERSE MYELITIS ; A RARE PRESENTATION OF DIFFUSE LARGE B-CELL LYMPHOMA

Darshyini R, El Gan, Sg Toh

Haematology Unit, Department of Medicine, Hospital Tuanku Jaafar Seremban

Background: Lymphomas are a malignancy of lymphoid cells, broadly categorised into Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of NHL worldwide.

Here we report a 62 year old malay man with a rare manifestation of transverse myelitis as a presenting finding in a case of DLBCL. It is diagnostically challenging as the chief complaint will prompt clinician to look in neurological aspect first.

Case report: A 62-year-old gentleman, presented with bilateral lower limb weakness for three days, sudden onset and progressively worsening. He complained of back pain , urinary incontinence and unable to open bowels for three days .On further history, he also lost weight.

On examination, power over bilateral lower limbs were 0/5 with a sensory level at T10. Blood investigation revealed hemoglobin level of 105g/L, white cell count of 7.5 109/ and platelet of 49 109 /L. Magnetic resonance imaging of whole spine done on 1/1/2021 showed diffuse myelitis changes at cervical and lumbar with nerve root impingement. Cerebrospinal(CSF) fluid analysis showed raised protein 0.45g/L , cytology showed acellular smears. Peripheral blood film was also done in view of anemia and thrombocytopenia , revealed 8% blast cell. Bone marrow aspirate and trephine showed evidence of DLBCL present in blood circulation and marrow. Computerized tomography thorax, abdomen, pelvis(CTTAP) showed paraspinal soft tissue mass/thickening at T9-T11.

He was initially diagnosed with transverse myelitis secondary to paraneoplastic syndrome. For the initial treatment patient was commenced on Intravenous Methylprednisolone .When the patient was confirmed to have DLBCL, he was treated with chemotherapy consisted of cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) with intrathecal Methotrexate initially, followed later by Methotrexate based chemotherapy regimen. Post 2 cycles of chemotherapy, his lower limb powers improved to 3/5.

6 months later, upon completing chemotherapy on 30th June 2021 ,CT TAP showed the previously seen right T9-T11 paraspinal mass resolved. Clinically patient no longer depends on CBD and his lower limb power improved to 4/5. Unfortunately his disease relapsed shortly after completion of chemotherapy and he succumbed to progressive DLBCL in October 2021.

DiscussionLymphoma can present with neurological involvement in two ways : direct invasion of tumor into spinal cord or immunogenic paraneoplastic syndrome which can appear as myelopathy. In this case initial MRI showed diffuse myelitis changes which was thought to be transverse myelitis. The follow up CT showed paraspinal mass invading spinal cord. Significant neurological improvement were seen post chemotherapy. This case highlights the importance of pursuing specific cause of myelopathy.


Ab

stract - C

S CR

Clin

ical

CC15

METHOTREXATE ACUTE ENCEPAHLOPATHY IN B LINEAGE ACUTE LYMPHOBLASTIC LEUKEMIA

Kam Hoo Yip1, Zhao Sheng Bong1, Yang Liang Boo1, Christopher Chin Keong Liam1, Azizan Sharif1, Soo Min Lim1

1 Hospital Sultanah Aminah (HSA) Johor Bahru, Malaysia

[email protected]

Background: Methotrexate (MTX) acute encephalopathy is rare clinical condition which usually presented with various clinical neurological manifestation. Some of the symptoms are headache, confusion, seizures, disorientation and focal neurological deficits. This condition is highly associated with the use of high dose methotrexate (HD-MTX). HD-MTX is a folate antimetabolite used as back bone in the treatment of B-lineage Acute Lymphoblastic Leukemia (ALL). It is known to cause toxicity in 2 to 12% of cases. MTX acute encephalopathy has been reported in 0.8% of cases in HD-MTX.

Case Report: A case of 18 year old young gentleman with Philadelphia negative B-lineage ALL (Ph negative B-ALL) diagnosed in early June 2021. He has underlying Ankylosing Spondylitis with HLA-B27 positivity on oral Sulfasalazine 1 gram BD. He first presented with few episodes of haematemesis and malaenic stools. Bleeding tendency is associated with lethargy, dizziness and reduced effort tolerance. Routine blood test showed pancytopenia with Hb 5.5, WCC 3.7, Plt 35 with elevated serum LDH 2189 and uric acid 896. Coagulation profile was normal and no signs of coagulopathy. Upper gastrointestinal scope showed multiple gastric polyposis and antral gastritis without obvious bleeding source. Diagnosis of B-ALL confirmed with peripheral blood film and diagnostic bone marrow assessment. Peripheral blood showed 19% moderate in size blast with open chromatin and inconspicuous nucleoli. Bone marrow immunophenotyping showed 26% abnormal blast. Trephine biopsy showed hypercellular marrow with prominent homogenous population of mononuclear cells, majority cells are blast cells. He started on intermediate risk (IR) Malaysian-Singapore Leukaemia Study Group 2020 (MASPORE) chemotherapy protocol which consist of HD-MTX at 5g/m2 and IT MTX. He had a desired response to induction chemotherapy evidence by a negative minimal residual disease (MRD) (<0.01%). He then received MASPORE (IR) M#2 which comprising of HD-MTX 5g/m2. Upon day 5 of HD-MTX, he presented with progressive altered mental state and inability to obey command. No fitting was witnessed. Upon arrival to our centre at day 7 of HD-MTX, Glasgow Coma Scale was E4V2M5 with blank stare. Neurological examination of upper and lower limbs revealed generalised hypotonia with normal reflex, absent clonus jerk as well as a negative Babinski sign. Cerebral spinal fluid did not show malignant cells nor any positive culture to suggest meningitis. Non contrasted CT brain showed foci of white matter hypodensity at right frontal and left parietal lobe which suggest MTX related encephalopathy. Patient received IV aminophylline as well as IV folinic acid for total of 5 days. MTX level was never above toxicity level prior and during this admission. MRI brain was unable to proceed during this admission as patient was restless.

Discussion & Conclusion: The onset of MTX encephalopathy usually takes place within 2 weeks of exposure to MTX. It could happen when MTX given via intravenous or intrathecal. The pathophysiology of this condition is not clearly understood. Mainstay treatment of MTX acute encephalopathy is to discontinue MTX. Agents such as corticosteroid, folinic acid and aminophylline are shown to be beneficial in treating this condition.


Ab

stract - C

S CR

Clin

ical

Ab

stract - C

S CR

Clin

ical

CC16

PARANEOPLASTIC DEGENERATION IN HODGKIN LYMPHOMA

Azhreen F Mohamad Azudin1, Toh See Guan1

1Department of Medicine Hospital Tuanku Jaafar Seremban (HTJS), Seremban, Negeri Sembilan, Malaysia

[email protected]

Background: Hodgkin Lymphoma is a lymphoproliferative disorder which typically presentes with lymphadenopathy, fever, weight loss and night sweats. Paraneoplastic syndrome is a group of symptoms that occur at a site distant from the tumour or site of metastases. It is believed to be an abnormal response of the immune system in relation to the cancer cells. Paraneoplastic cerebellar degeneration (PCD) is an uncommon presentation for Hodgkin Lymphoma. PCD has been reported to occur in malignancy of the lungs, ovaries and lymphomas. We describe a case of Nodular Sclerosing Hodgkin Lymphoma which was complicated with PCD.

Case Report: 37-year-old gentleman with no known medical history presented with multiple neck swellings, fever and weight loss for 3 months. He underwent lymph node biopsy in November 2021 in a private hospital which confirmed Classical Hodgkin Lymphom Nodular Sclerosing subtype. After a period of defaulting he re-presented in April 2022. During the second encounter he complained of progressive unsteadiness, giddiness and syncope in the past five months. Central nervous system (CNS) examination showed positive cerebellar signs alone with mild dysarthria, bilateral nystagmus, dysdiadochokinesis and past pointing. A brain contrasted computed tomography (CT) scan was negative for brain parenchymal lesion or leptomeningeal enhancement. A magnetic resonance imaging, angiography and venography (MRI/MRA/MRV) of the brain with Gadovist contrast showed no evidence of thrombosis. Echocardiogram excluded cardiac thrombus or vegetation. He was seen by Neurologist and was treated with intravenous immunoglobulin (IVIG) 0.4g/kg/day for 5 days. He was empirically treated for meningoencephalitis with intravenous Acyclovir 500mg tds for 14 days. Cerebral spinal fluid (CSF) analysis showed glucose 2.91mmol/L, protein 0.3g/L, lactate 1.46mmol/L, acellular cytology smear with no malignant cells and negative for Cryptococcal antigen, Indian ink and acid fast bacilli. Concurrent random blood glucose was 5.9mmol/L. CSF paraneoplastic panel was sent to Institute Molecular Research Kuala Lumpur (IMR) but not run due to temporary suspension of the test. His initial counts was Hb 9.6 g/L TWC 10.5 x10^9/L Platelet 424 x10^9/L. Upon completion of his IVIG he underwent first cycle of doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy. He is planned for total 6 cycles of chemotherapy with an interim CT to monitor his progress.

Discussion & Conclusion: CNS involvement of Hodgkin Lymphoma is very rare occuring less than 0.02%. It can occur via direct metastases or indirect spread as a result of paraneoplastic syndrome or treatment related neuropathies. Diagnostically one can test for anti-Tr and anti-mGluR1 antibodies which are directed towards Purkinje cells which cause irreversible cerebellum atrophy. Cerebellar syndromes mostly precedes the diagnosis of Hodgkin Lymphoma which is the opposite in our case. We expect PCD to either improve with chemotherapy, resolve spontaneously or become progressively fatal. Although it would be beneficial if the CSF paraneoplastic panel were available to diagnose PCD, the absence of positive imaging excludes the possibility of a direct metastases. Considering the ABVD regime is not intended for diseases affecting the CNS and the improvement in the patient’s clinical response during follow up supports the diagnosis of PCD in Hodgkin Lymphoma.


Ab

stract - C

S CR

Clin

ical

CC17

PARAPLEGIA IN ACUTE LYMPHOID LEUKEMIA: A CASE SERIES

Tien Gen Wong , Kim Wah Ho, Jerome Tan, Sharifah Shahnaz SAK, Sen Mui Tan

Hematology Department, Hospital Ampang, Selangor, Malaysia

[email protected]

Background: Acute lymphoblastic leukemia (ALL) accounts for 20% of all adult acute leukemias. CNS prophylaxis is always incorporated in ALL treatment protocol, as intrathecal (IT) chemotherapy, cranial irradiation or high dose systemic chemotherapy, which significantly reduced CNS recurrence. IT methotrexate treatment rarely causes myelopathy, a complication that is potentially fatal.

Case Report / Case Series: Case(1) 26-year-old man with Ph+ B-ALL, treated with GMALL induction with imatinib, followed by MIDAC, 2 cycles of HyperCVAD regime. He received a total of 10 IT methotrexate (MTX). 1 month after his last treatment, he developed progressive ascending lower limb numbness and weakness with a sensory level at T10. MRI spine urgent shows normal spinal cord, however repeated MRI 3 weeks later shows dorsal column hyperintense signal. CSF examination for paraneoplastic antigen autoimmune profile, flowcytometry and viral panel, shows normal result. Treatment with methylprednisolone, IVIG and high dose vitamin B12 were not effective. His disease relapsed later, and he passed away.

Case (2) 33-year-old man, with T-lymphoblastic lymphoma and leptomeningeal involvement. He was treated with 3 cycles of BFM block A and B chemotherapy, with 2 weekly triple IT chemotherapy, with clearance of CSF blast after 3 IT chemotherapies. He received total of 10 IT chemotherapy .1 month after his last chemotherapy, he developed ascending sensory motor neuropathy. MRI spine urgent shows normal spinal cord and nerve conduction study shows asymmetrical motor polyneuropathy. He was given another triple IT chemotherapy, and since then his lower limbs power became 0/5. Treatment with methylprednisolone, IVIG, high dose folinic acid and Vitamin B12 were not effective. He subsequently passed away due to pneumonia.

Case(3) 31-year-old man, with T-ALL, he was treated with 2 cycles of HyperCVAD and subsequently achieve remission. Further treatment was delayed due to covid infection, thus he relapsed. He was salvage with nelarabine, cyclophosphamide and etoposide, with triple IT chemotherapy. He received 8 times of intrathecal chemotherapy. He subsequently developed ascending sensorimotor neuropathy, with sensory level at L1. MRI spine shows normal spinal cord. Treatment with methylprednisolone, IVIG, high dose folinic acid and Vitamin B12 were not effective. Repeated CSF examination shows no evidence of leukemic blast. He is still under evaluation by neuro-medical team.

Discussion & Conclusion: MTX induced myelopathy is a rare but serious subacute complication from MTX based treatment, especially given through intrathecal route. MRI can be normal or resemble findings of subacute combined degeneration of cord. MTX can interfere with the folate-methionine cycle, leading to reduced production of S-adenosylmethionine (SAM), thus causing demyelination of spinal cord. There is no effective treatment for MTX induced myelopathy, in fact, supplementation with methionine and SAM and resulting in clinical improvement was reported in a few case reports. Genetic polymorphism in methylene-tetrafhydrofolate reductase (MTHR) or thymidylate synthase (TYMS) gene might be the reason of occurrence of IT MTX induced myelopathy in certain patients. MTX induced myelopathy following IT MTX is a diagnosis of exclusion for our patients. Patients’ outcome is poor due to the delayed in recognition, as CNS leukemia is usually the first diagnosis and patient will receive further IT chemotherapy.


Ab

stract - C

S CR

Clin

ical

Ab

stract - C

S CR

Clin

ical

CC18

PITFALLS IN THE DIAGNOSIS OF A RELAPSED LYMPHOMA

Bee Sun Lee1, Siew Lian Chong2, Noraidah Masir3, Sen Mui Tan2

1 Universiti Tunku Abdul Rahman, Selangor, Malaysia;2Hematology Department, Hospital Ampang, Selangor, Malaysia;3Prince Court Medical Centre, Kuala Lumpur, Malaysia

[email protected]

Background: Lymphoma pathology remains a challenging field. Following case illustrates the possible pitfalls that could have led to the inaccurate diagnosis of a lymphoma.

Case Report: A 33-year-old gentleman presented with bilateral cervical swelling associated with B symptoms. Clinically, he had painless bilateral cervical lymphadenopathy. A CT scan showed a stage II disease. Excisional biopsy of cervical node showed infiltration by atypical large lymphoid cells, which immunohistochemistry (IHC) demonstrated positivity for CD20, CD30, BCL6 and MUM1, and negative for CD3 and CD10, consistent with diffuse large B-cell lymphoma (DLBCL), ABC-subtype. Patient underwent 6 cycles of dose-adjusted R-EPOCH followed by 2 cycles of high-dose methotrexate. End-of-treatment CT showed complete remission. However, patient returned after 2.5 years complaining of a right-sided chest wall swelling associated with breathlessness on lying. A repeat CT revealed an anterior right chest wall intramuscular mass measuring 6.2 x 6.1 x 7.9cm extending to the right pleura with multiple enlarged nodes at the left and anterior cardiophrenic angle. A clinical diagnosis of relapsed DLBCL was made. As patient was symptomatic, he was immediately commenced on salvage chemotherapy. After his first chemotherapy, unfortunately the mass has increased in size. Hence the mass was biopsied. There were areas of medium to large atypical cells with prominent central nucleoli and minimal cytoplasm, which stained positively for CD45 and BCL6, and were negative for CD20, CD79a and CD10. Ki67 was 60%. It was concluded that the pan B-cell markers were not recognized in the large cells due to previous chemoimmunotherapy. It was reported as relapsed DLBCL. However the response remained poor even after his 2nd chemotherapy, hence the mass was re-biopsied. It again showed atypical moderate-sized lymphoid cells arranged in a diffuse pattern, IHC staining showed BCL6+, MUM-1+ and CD20-, CD79a-, PAX5-, CD34-. Ki67 was 50-60%. It was concluded as relapsed DLBCL. Patient eventually underwent 4 cycles of chemotherapy followed by radiotherapy to the mass. However, a repeat assessment showed a less than partial response. Hence, another histopathologist’s opinion on the case was consulted. The histopathologist re-looked at all the samples with additional IHC staining. It was discovered that the large atypical cells are infact PAX5+, CD30+, CD15+ (focal) and MUM-1+ with accompanying surrounding small lymphocytes and occasional histiocytes. The findings were suggestive of a classical Hodgkin Lymphoma (cHL). With the revised diagnosis, treatment was re-strategized followed by an autologous stem cell transplantation. Since then, patient has remained well.

Discussion & Conclusion: This could be a case of Large B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and cHL. The first cervical node biopsy could have been taken from the DLBCL component and after chemotherapy, the DLBCL component has disappeared leaving behind the cHL component, which was picked up during the relapse. This case highlights that insufficient use of immunostains could have lead to the inadequate diagnostic precision in the relapsed samples. Awareness of common situations leading to diagnostic error in the field of lymphoma pathology is important besides a regular discussion between the clinicians and pathologists.


Ab

stract - C

S CR

Clin

ical

CC19

SUCCESS SERIES OF A RARE LEUKEMIC VARIANT- BPDCN (BLASTIC PLASMACYTOID DENDRITIC CELL NEOPLASM) - A SINGLE CENTRE EXPERIENCE

Khaiteri R1, Shan Shan Tan1 , Wilfred Gilbert1, Lee Lee Wong Lily1

1 Hematology Unit, Medical department , Hospital Queen Elizabeth, Sabah

[email protected]

Background: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive and rare hematopoietic malignancy derived from precursor plasmacytoid dendritic cells. Most BPDCN patients present typically with skins lesion which later involve the bone marrow , lymph nodes and other organs.

Case series: We report 2 cases of BPDCN treated at our centre using ALL type chemotherapy regime- MASPORE (Malaysia- Singapore) protocol.

Case( 1) A 15 year old male presented with a 2 weeks history of purplish lesions over his chest and back and pancytopenia in February 2020. A Bone marrow aspiration and trephine biopsy confirmed the diagnosis of BPDCN with a concomitant similar skin biopsy finding. He had multiple cervical lymphadenopathy as well. He was started on MASPORE Intermediate risk B-ALL protocol whereby he achieved a complete morphological remission and disappearance of skin lesions after first cycle of chemotherapy. He was then further consolidated with continuation of the MASPORE protocol and referred for fully matched sibling donor allogeneic stem cell transplant in October 2020. His transplant was uneventful. He is currently 20 months post transplant and is in complete remission with the latest BMAT showing 99.7% donor chimerism.

Case (2) A 44 year old lady presented with a 2 months history of purplish grey nodular swelling over her face, arms and upper back. In July 2021 she was referred to the dermatology team for a biopsy which confirmed BPDCN after which she was referred to haematology.Her blood counts were fairly normal at presentation however a BMAT was consistent with a diagnosis of BPDCN. She was started on MASPORE protocol after which she went into remission after the first cycle of chemotherapy. She has been in remission as of date and is planned for allogeneic stem cell transplant soon.

Discussion: BPDCN is a rather rare entity and challenging to diagnose and treat. With newer diagnostic criteria’s and more information into the immunophenotypic characteristic and cell morphology this diagnosis is gaining popularity. The classical presentation of cutaneous lesions and pancytopenia coupled with typical immunophenotype finding of CD123, CD4, CD56 (123456) is in accordance with this diagnosis. As evidenced by the two cases treated at our centre ALL- like regime using MASPORE protocol followed by allogenic stem cell transplantation seems to be a promising treatment regime for this condition and it has shown to give a high response rate and associated with low toxicity profile.

Conclusion: Induction with MASPORE protocol followed by consolidation with allogenic hematopoietic stem cell transplant is associated with a high success rate in treating this rare condition.


Ab

stract - C

S CR

Clin

ical

Ab

stract - C

S CR

Clin

ical

Ab

stract - C

S CR

Lab

ora

tory

SUCCESSFUL TREATMENT OF DISSEMINATED FUSARIUM INFECTION WITH ENDOPHTHALMITIS IN A PATIENT WITH ACUTE MYELOID LEUKEMIA

Zhi Yuan Lee1, Tze Shin Leong1, Grace Wan Chieng Lee1, Sin Yeh Li1, Hock Hin Chua2, Aiful bin Ahmad3, Ruzanna Dayanna Zawawi3, Pee Xu Kent4, Lee Ping Chew1

1Hematology Unit, Medical Department, Sarawak General Hospital, Kuching, Malaysia;2Infectious Disease Unit, Medical Department, Sarawak General Hospital, Kuching, Malaysia;3Pathology Department, Sarawak General Hospital, Kuching, Malaysia;4Ophthalmology Department, Sarawak General Hospital, Kuching, Malaysia

[email protected]

Background: Fusarium spp. are the second leading cause of disseminated fungal infections in human. Fusarium spp., a group of filamentous fungi which are predominantly found in soil and plant, produce fumonisins and trichothecene toxins. It may cause fatal infection in immunocompromised patients especially those with occupational risk factors. This case report illustrates a patient with newly diagnosed acute myeloid leukemia (AML) who had undergone induction chemotherapy but complicated with disseminated Fusarium solani infection.

Case Report / Case Series: A 47 years old lady, working as a farmer, was diagnosed with acute myeloid leukemia and started on induction chemotherapy DA (3+7). She developed neutropenia on day 10 of chemotherapy. On day 12 of chemotherapy, she experienced fever, myalgia and bilateral lower limbs swelling followed by eruption of generalized skin lesions, resembling fungal spots. The skin lesions started from both upper and lower extremities sparing the palms and soles, spread rapidly to the trunk and face, involving the soft palate and tongue. Blood culture yielded Fusarium solani and patient was started on intravenous amphotericin B. Skin biopsy culture grew the same organism while histopathology examination showed moderate to marked neutrophilic infiltrates forming abscess in dermis. Patient started to develop left eye redness with blurring of vision on day 14 of chemotherapy (after started on intravenous amphotericin B). Slit lamp examination revealed hypopyon with filamentous appearance and aggregate of fibrin over the anterior chamber at the peripheral iris suggestive of fungal endophthalmitis. Intravitreal sample sent was negative for potassium hydroxide staining and culture. Intravitreal amphotericin B was administered for 5 days together with intravenous amphotericin B. The mucocutaneous and eye lesions resolved while her visual acuity improved after 2 weeks treatment of intravenous amphotericin B and 4 weeks of tablet voriconazole.

Discussion & Conclusion: Disseminated Fusarium infection may complicate chemotherapy treatment and can be life threatening in immunocompromised patients. It is usually associated with poor outcome due to treatment failure. To the best of our knowledge, this is a rare case of disseminated Fusarium solani infection with endogenous endophthalmitis which is successfully treated with combination of intravenous amphotericin B and tablet voriconazole. Mucocutaneous manifestation is frequently the initial presenting feature even in the absence of fever. High index of suspicion and early identification is required in order to institute prompt and appropriate treatment especially in patients with occupational risk factors such as farming.

CC20

Ab

stract - C

S CR

Clin

ical


Ab

stract - C

S CR

Lab

ora

tory

cl1

A RARE CASE OF CO-INHERITANCE HAEMOGLOBIN CHARLIEU [α106(G13) Leu →Pro (α2)] WITH SOUTH EAST ASIAN OVALOCYTOSIS

Nurul Hidayah Musa1, Norafiza Mohd Yasin1, Yuslina Mat Yusoff1, Ermi Neiza Mohd Sahid1, Azian Naila Md Nor1, Faidatul Syazlin Abdul Hamid1, Syahzuwan Hassan1, Aisyah Aziz1, Haifa Hanani Mohd Zaki1, Liew Chuin Hen2, Noor Amalia Bakri3, Ezalia Esa1

1Haematology Unit, Cancer Research Centre (CaRC), Institute for Medical Research (IMR), National Institute for Health (NIH) Setia Alam, Selangor, Malaysia;2Department of Paediatric, Hospital Tuanku Ampuan Najihah, Kuala Pilah, Negeri Sembilan, Malaysia; 3Department of Pathology, Hospital Tuanku Ampuan Najihah, Kuala Pilah, Negeri Sembilan, Malaysia

[email protected]

Background: As per date, only two publications were found to describe this rare alpha variant, Hb Charlieu [α106(G13) Leu →Pro (α2)]. Therefore, we would like to support their findings and highlight this unique variant. Heterozygous Hb Charlieu was previously reported to be phenotypically silent with only a slightly lowered MCV and MCH with no detection of abnormal haemoglobin (Hb) variant from Hb analysis. However, this study presents a new-born with a moderate to severe haemolytic anaemia requiring blood transfusion. To the best of our knowledge, this is the first case report of co-inheritance Haemoglobin Charlieu with South East Asian Ovalocytosis (SAO) in the Malaysian population.

Case report: 2-month-old Malay boy, presented with neonatal onset of anaemia with Hb of 5.8g/dL. His full blood count (FBC) showed hypochromic microcytic anaemia, with RBC, MCV, MCH, RDW, and retics were 1.89x1012/L, 100.0fL, 30.7pg, 24.8% and 7.81% respectively. Physical examinations showed moderate hepatosplenomegaly. Peripheral blood film (PBF) showed RBCs morphology features of SAO with underlying thalassaemia picture. Haemoglobin analysis by using capillary electrophoresis (CE) revealed normal findings with no apparent abnormal peak. No H or Bart’s peaks were found. Molecular analysis for common deletional and non-deletional alpha thalassaemia showed negative findings. Direct sequencing for the alpha globin gene confirmed the presence of Heterozygous state of α2 Codon 106 (CTG>CCG) Hb Charlieu mutation. Molecular analysis for beta -thalassaemia mutation showed no abnormality detected.

Discussion & Conclusion: Co-inheritance of Hb Charlieu with SAO has never been described before. This variant was reported as hyper-unstable variant that led to assemble defect to form stable tetramers. Even in homozygous state, no abnormal peak was detected in Hb analysis. Even though this variant is phenotypically silent in heterozygous, it was reported as a severe phenotype in homozygous state or co-inheritance with beta thalassaemia variant. The presence of membranous disorder in this case could potentially aggravate the haemolytic features. The detection of this variant is important to prevent potentially severe α-thalassaemia in future generations.


Ab

stract - C

S CR

Lab

ora

tory

Ab

stract - C

S CR

Lab

ora

tory

CL2

A RARE CASE OF PARA-BOMBAY A ASSOCIATED WITH ANTI-H, ANTI-MIA AND POSSIBLE ANTI-M1 IN AN UNIVERSITY HOSPITAL

Evelyn Teng Mei Yuong1, Rabeya Yousof2, Nor Fadzliana2, Nur Afifah Suhemi2, Tang Yee Loong1,2

1Department of Pathology, Universiti Kebangsaan Malaysia Medical Centre, Cheras, Kuala Lumpur;2Blood Bank unit, Department of Diagnostic and Laboratory Services, Universiti Kebangsaan Malaysia Medical Centre, Cheras, Kuala Lumpur

[email protected]

Background: Para-Bombay blood phenotype is a rare blood group among all populations. This blood group is characterized by either completely lack of H antigen or having small amounts of H antigen on the red blood cells but presence of ABH secretor substances in the body secretion and plasma. When there is a demand for blood transfusion, para-Bombay may be misinterpreted as group O and the transfusion of group O packed cells may cause fatal haemolytic transfusion reaction (HTR). We report a rare case of para-Bombay A (Ah) phenotype with multiple red cells’ antibodies.

Case report: A 37-year-old lady with underlying end-stage renal failure was electively admitted for surgical excision of left giant fistula. She was diagnosed as Ah in 2016 at Seremban hospital and was transfused with red cells. She has 4 siblings in the family and one of her sisters is known to have a Bombay phenotype. On examination, she was haemodynamically stable. Full blood count showed mild normocytic normochromic anaemia with Hb of 11g/dL. A blood sample was sent for group, screen & hold (GSH). Forward grouping with antisera A showed 1+ reaction, no reaction at antisera B while reverse grouping with known B cells showed 4+ reaction, w+ reaction at known O cells and no reaction at A1 cells. H lectin test was negative. Lewis phenotyping was done and the Le(a-b+) result confirmed that she was an ABH secretor. RhD typing showed 4+ reaction. Rhesus phenotyping showed that her likely genotype was R1r (DCe/dce). The direct antiglobulin test (DAT) was negative. Antibody screening was positive and antibody identification revealed anti-Mia and possible anti-M1. One unit of Mia-, Bombay (Oh) phenotype, RhD+, crossmatch compatible blood was obtained from National Blood Centre. The surgery was uneventful. No blood transfusion was given and she was discharged with a Hb of 10.2 g/dL.

Discussion & Conclusion: This case exhibits a rare phenotype blood group associated with multiple red cells’ antibodies. Para-Bombay is a rare phenotype and only limited cases were reported worldwide. The para-Bombay individuals can develop anti-H and/ or anti-IH in addition to naturally occurring anti-A and/or anti-B. The two antibodies may display wide thermal amplitude reactivity (4°C to 37°C) with all red cells except Oh or para-Bombay red cells. This patient was sensitized and developed anti-Mia and anti-M1 antibodies due to the previous transfusion. Anti-H is a clinically significant antibody that capable of fixing complement and leading to acute HTR. Anti-Mia is also reported to cause HTR and haemolytic disease of foetus and newborn. Ideally, Mia-, Ah or Oh, RhD+, crossmatch compatible red cells should be selected for this patient. Unfortunately, H-deficient red cells unit are not readily available in most circumstances. Nevertheless, in the case of emergency situation and absence of H-deficient red cells, ABO specific/compatible, crossmatched compatible blood may be used with caution provided the patient’s anti-H or anti-IH showed no reactivity at 37°C.


Ab

stract - C

S CR

Lab

ora

tory

CL3

A RARE CASE OF T ACUTE LYMPHOBLASTIC LEUKAEMIA (T-ALL) WITH MINOR BCR::ABL1

Siti Shahrum Muhamed Said, Shenaz Banu Said Khan, Norazlina Azman, Nurimatussolehah Sarijan, Suzana Zainol, Mimi Azura Aziz

1Pathology Department, Hospital Tunku Azizah, Kuala Lumpur

[email protected]

Background: Acute lymphoblastic leukemia represents 25% of all pediatric malignancy with T-ALL accounts for approximately 12-15% of all newly diagnosed ALL cases. T-ALL is an aggressive disease and patients often present with a high tumor burden with hyperleukocytosis, and/or bulky mediastinal mass. The Philadelphia chromosome, the hallmark of Chronic Myeloid Leukaemia (CML) results from a reciprocal translocation between the long arms of chromosomes 9 and 22. This translocation involves the transfer of the ABL1 gene on chromosome 9 to the breakpoint cluster region (BCR) of chromosome 22, resulting in fused BCR::ABL1 gene. BCR::ABL1 fusion gene is also present in a subset of ALL and rare cases of AML, B-cell lymphoma, and T-cell lymphoma. We report a rare case of de-novo minor BCR::ABL1-positive T-ALL in a pediatric patient.

Case report: A 16-year-old girl presented with low-grade fever, hepatosplenomegaly, and multiple cervical lymphadenopathies. Full Blood Count showed leukocytosis with bicytopaenia - white blood cell count 54.5x109/L, hemoglobin 9.5 g/dl and platelet 68x109/L. Full blood picture revealed presence of 86% blasts. Anterior mediastinal mass was noted on CXR. Bone marrow aspirate (BMA) and immunophenotyping (IPT) were consistent with T-ALL. Molecular cytogenetics by Fluorescence in situ hybridization (FISH) identified BCR::ABL1 rearrangement. She was started on dexamethasone and referred to our center for further management. Repeat BMA and IPT at our center showed similar findings. Cerebrospinal fluid IPT showed numerous T lymphoblasts. Conventional cytogenetics showed a complex karyotype with no Philadelphia chromosome detected. Interphase FISH identified BCR::ABL1 fusion gene and molecular analysis showed minor BCR::ABL1 (p190, e1a2). She was treated with chemotherapy and Dasatinib. She underwent Matched Unrelated Donor stem cell transplantation, however, she succumbed post transplantation.

Discussion: BCR::ABL1-positive T-lineage acute leukemia is extremely rare; the differential diagnosis includes de-novo BCR::ABL1-positive T-ALL or T cell lymphoblastic crises of CML. Due to the rarity of the disease, the incidence, clinical behavior, prognosis, and therapeutic implications of the BCR::ABL1 in T-cell lymphoid leukaemia are not well defined. Distinguishing de novo BCR-ABL1-positive T-ALL from T-cell lymphoblastic crisis of CML can be challenging. Previous history of CML, older age, marked extra-medullary involvement, massive splenomegaly, presence of increased number of residuals circulating granulocytic precursors, eosinophils, and basophils, presence of major BCR::ABL1 breakpoint transcript and excellent response to tyrosine kinase inhibitors (TKIs) favors a T cell lymphoblastic crisis of CML. Presentation at younger age with bone marrow involvement by numerous blasts and presence of minor BCR::ABL1 transcript favors de-novo BCR::ABL1-positive T-ALL. Correlation between clinical, morphological, cytogenetics, FISH and molecular findings are essential in distinguishing between these two entities. Our patient does not have a previous history of CML. She presented with numerous blasts in the bone marrow and CSF. Molecular analysis by RT-PCR confirmed the presence of minor BCR::ABL1 transcripts. These findings support the diagnosis of de-novo BCR::ABL1-positive T-ALL in our patient.


Ab

stract - C

S CR

Lab

ora

tory

Ab

stract - C

S CR

Lab

ora

tory

CL4

CASE SERIES: THE MOLECULAR LANDSCAPE OF CHRONIC MYELOID LEUKAEMIA PATIENTS EXPERIENCING TREATMENT-FREE REMISSION FAILURE

Siew Lian Chong1, Asral Wirda Ahmad Asnawi1, 2, Tien Gen Wong1, Pek Kuen Liew1, Sharifah Shahnaz Syed Abd Kadir1, Tee Chuan Ong1, Jerome Tan1, Kim Wah Ho1, Veena Selvaratnam1, Sen Mui Tan1

1Department of Hematology, Hospital Ampang, Selangor, Malaysia; 2Faculty of Medicine and Health Sciences, Universiti Sains Islam Malaysia, Negeri Sembilan, Malaysia.

[email protected]

Background: The practice of indefinite tyrosine kinase inhibitors (TKIs) provision for Chronic Myeloid Leukemia (CML) has remained unchallenged. TKI cessation has been practised in many major haematological centres with patients achieving deep molecular remission for >2 years being suitable candidates. However, failure to sustain treatment-free remission (TFR) status is still a problem. Therefore, we aimed to investigate the molecular evolution to explain the loss of molecular remission in a small subset of patients with TFR failure by using next generation sequencing.

Case series: Patient A and patient B diagnosed to have CML for at least 4 years and in deep molecular response for at least 2 years were recruited for TFR trial and were closely monitored by monthly BCR-ABL molecular quantification. However they failed after TKI cessation. Three time points of PCR taken for both patient, which screening, first visit and relapsed. An RNA sequencing analysis was performed using DNBSeq G400 sequencer. The library to analyse the coding transcriptome was prepared using MGIEasy RNA Directional Library Prep Set. An average of 233 million reads were generated for each sample, mapped to the reference genome and analysed. Based on principal component analysis, the three time points were clustered with each other and did not show any significant genes associated to oncogenes in Patient A. However, for Patient B the time points were distinct with few significant genes related to oncogenes identified. CAMP, DEFA1B, DEFA3, LCN2 and DEFA1B were downregulated in the first visit and second visit in comparison to screening.

Discussion & Conclusion: DEFA3 and DEFA1B are known to affect transcriptional misregulation in cancer, while LCN2 is known to have interaction in IL-17 signalling pathway. This preliminary observation identified oncogenes that may play a role in TFR failure. More time points and replicates are required for further verification.


Ab

stract - C

S CR

Lab

ora

tory

CL5

COLD AGGLUTININ (CA) - ASSOCIATED LYMPHOPROLIFERATIVE DISEASE (LPD), A NEW DISEASE ENTITY

Fatin Adlia Arifin1, Kim Yan Poh1

1Department of Pathology, University of Malaya Medical Centre, Kuala Lumpur, Malaysia.

[email protected]

Background: Primary cold agglutinin disease (CAD) has been traditionally used to refer to cold autoimmune haemolytic anaemia (CAIHA) in the absence of underlying disease (infection, autoimmune, lymphoma and malignancy). Despite the lack of overt clinical and radiological evidence of underlying lymphoma, this group of patient has been shown to harbour B-LPD in the marrow with homogeneous features to suggest a disease entity that is different from hitherto well described non Hodgkin B-lymphoma in the World Health Organization classification.

Case report: A 81-year-old gentleman presented with CAIHA since 2016. He had symptomatic anaemia and required frequent transfusions. Clinically, he appeared pale and jaundiced, with no palpable lymph nodes or hepatosplenomegaly. Initial blood investigation showed severe anaemia (Hb 4.1g/L) with positive haemolytic markers (reticulocytosis, raised unconjugated bilirubin, raised lactate dehydrogenase, low serum haptoglobin) and positive direct antiglobulin test with C3d only. There was presence of CA with no detectable activity at 37°C (CA titre not done). Peripheral blood film showed marked red cell agglutination without lymphocytosis or abnormal lymphoid cells observed. Serum protein electrophoresis showed paraprotein (3g/L) of IgM Kappa. Computerized tomography of thorax abdomen and pelvis showed only a mildly enlarged spleen of 14.1cm with no evidence of lymphadenopathy.

Bone marrow aspirate showed erythroid hyperplasia. Despite no lymphocytosis, flow cytometry was carried out with the hope to catch a small population of clonal B cell and indeed, 3% were identified with the following antigen expression: CD19+/CD20+/CD5-/CD10-/CD23-/CD200-/sIgM+/sIgD+/FMC7+/CD43-/Kappa restriction. On trephine biopsy, multiple interstitial lymphoid follicles were found. These follicles were composed of B cells and T cells (T>B), with remarkable rimming of plasma cells surrounding the lymphoid nodules. Monoclonal immunoglobulin heavy chain gene (IGH) rearrangement was detected while T-cell receptor (TCR) rearrangement study showed polyclonal.

Discussion & Conclusion: The concept of CA-associated LPD emerged after systematic histopathology study published by Randen et al in 2014. This case displayed many immunophenotypic and histological findings that are classical to this provisional entity: no overt clinical or radiological findings of lymphoma/malignancy, absence of lymphocytosis, nodular infiltration of small B-cells, and rimming of plasma cells around these follicles. Of note, the follicles in this case composed of more T cells than B cells. This finding was perplexing at the beginning, however clonality of an apparent B cell had been well demonstrated by flow cytometry together with IGH and TCR rearrangement. KMT2D mutation, gain of chromosomes 3, 12 and 18 are found frequently in CA-associated LPD (not available in this case). However, marginal zone lymphoma (MZL) also shared similar findings, apart from exclusive disease in the bone marrow. Hence the possibility of this arguably new entity being related to MZL has also been raised. Clinician and pathologist need to be aware of this disease entity in search of the ‘primary’ cause of CAD, despite lack of lymphocytosis or clinical and radiological evidence of overt lymphoma. Lastly, the terminology of primary CAD is preferably reserved to describe CAIHAs that are “idiopathic” but in most (if not all) associated with this well-recognized entity of B-LPD.


Ab

stract - C

S CR

Lab

ora

tory

Ab

stract - C

S CR

Lab

ora

tory

CL6

EBV POSITIVE DLBCL-A RARITY

Hari Priya Raghvan1, Alia Suzana Asri1, Nurasyikin Yusof1, Tang Yee Loong1, Noraidah Masir1, Nor Rafeah Tumian2, Sivakumar Palaniappan2

1Department of Pathology, Universiti Kebangsaan Malaysia;2Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Cheras, Kuala Lumpur

[email protected]

Background: Epstein Barr Virus (EBV) positive Diffuse Large B-Cell Lymphoma (DLBCL) accounts for <5% of DLBCLs of the worlds’ population. They are mainly seen in the elderly and are believed to be related to immunosenescence and chronic inflammation. The morphological features consist of variable numbers of large cells, immunoblasts and Reed-Sternberg like cells. We report a rare case of EBV positive DLBCL highlighting on the morphological features.

Case report: An 82-year-old lady with underlying hypertension presented with fever, shortness of breath and left iliac fossa pain for 1 week with cough for 1-month. On examination, GCS was full. Patient was pale with bilateral periorbital ecchymosis and bruises over bilateral dorsal aspect of hands. No lymphadenopathy or organomegaly. Blood investigations revealed pancytopenia with leucoerythroblastic picture. No abnormal lymphoid or blast cell seen. Serum LDH and ferritin were markedly elevated. A CT abdomen showed multiple enlarged abdominal lymph nodes. Bone marrow aspiration were hypercellular with occasional abnormal mononuclear cells and presence of macrophages that engulf erythroblasts, leucocytes and platelets. Trephine biopsy showed pleomorphic cells with mostly large cells and Reed-Sternberg like cells. No increase in background inflammatory cell. They were confirmed as EBV positive DLBCL which shows positivity for CD30 and EBER-ISH among others. She was commenced on Rituximab and prednisolone, however, succumbed after one cycle of chemotherapy. Discussion & Conclusion: This case exhibits a rare case of EBV-positive DLBCL. A high degree of suspicions is needed in a case of elderly with lymphadenopathies. The morphological characteristics of pleomorphic cells and Reed-Sternberg like cells with no increase in non-neoplastic inflammatory background should raise a concern on this possible diagnosis. This should prompt us to proceed for EBER-ISH confirmation. The EBV-positive DLBCL is an aggressive disease hence early recognition is important for initiation of therapy.


Ab

stract - C

S CR

Lab

ora

tory

CL7

FANCONI ANEMIA FROM A NOVEL MUTATION DETECTED BY WHOLE EXOME SEQUENCING: A CASE REPORT

Rungrote Natesirinilkul1,2, Pimlak Charoenkwan1,2, Prapai Dejkhamron1, Maliwan Tengsujaritkul1,4, Siripong Tongjai3,4

1Department of Pediatrics;2Research Cluster of Thalassemia and Red Blood Cell Disorders;3Deaprtment of Microbiology;4Center of Multidisciplinary Technology for Advance Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand

[email protected]

Background: Fanconi anemia is one of inherited bone marrow failure syndromes (IBMFS). Although the phenotypes of the patients with anemia are pathognomonic, around half of the patients presents with the typical syndrome. In addition, to confirm the diagnosis, the chromosomal breakage study is required. However, that test is sophisticated and required the experienced specialists to perform. Currently, whole exome sequencing is widely used for diagnosing several inherited disorders including IBMFS which could provide more details than chromosomal breakage study and be more beneficial for genetic counselling.

Case report: A 2-year-girl, a preterm twin B, was referred to our hospital due to congenital hypothyroidism regarding the diagnosis of twin A who had been diagnosed with congenital hypothyroidism since birth on the neonatal screening tests. The physical examinations showed poor weight and height gain (< 3rd percentile), café-au-lait spots on left side of abdomen, left thigh and right side of back, hypotelorism, relative skin hyperpigmentation as compared to her parents, hypoplastic, floating and triphalangeal thumbs both sides which had been found since birth and microcephaly. The initial complete blood count at the age of 2 years showed normal Hb at 12 g/dL, WBC at 9,800/mm3 with absolute neutrophil count at 3,038 /mm3 and platelet count at 150,000/mm3. However, her MCV was high at 100 fL. She finally was diagnosed with hypothyroidism and received the treatment. During her course of treatment her CBC became thrombocytopenic, neutropenic and anemic at the age of 4, 6 and 8 years, respectively. The chromosomal breakage study showed 19% of abnormal cells with metaphases and the genetic study was confirmed subsequently by whole exome sequencing which revealed a novel mutation in FANCA gene at c.3629del, p.(Phe1210Serfs*37). Unfortunately, both her twin A and she died at age 10 and 12 years old, respectively due to recurrent bleeding manifestations and febrile neutropenia.

Discussion & Conclusion: Laboratory diagnosis of Fanconi anemia is crucial for suspicious children as it is required to be tested in the sibling who may be a donor for hematopoietic stem cell transplantation. However, the conventional genetic testing has several limitations to detect the mutations in a large gene like FANC gene with 80 kb and 43 exons. Even though common mutations of Fanconi anemia are usually found in FANCA, FANCC and FANCG, there is some ethnic predominance such as FANCA and FANCG which were commonly reported in Asian population such as Japanese and Korean population. This patient and likely her twin sister have the frameshift mutation in FANCA gene which correlates with their severe clinical manifestations at young age. Early diagnosis and intervention are the key to improve the outcomes of children with Fanconi anemia.


Ab

stract - C

S CR

Lab

ora

tory

Ab

stract - C

S CR

Lab

ora

tory

CL8

LOW PULSE OXIMETER READINGS IN A GIRL WITH UNSTABLE HAEMOGLOBIN KÖLN [GTG→ ATG, Val→ Met]: A CASE REPORT

Ruzanaz Syafira Ruzman Azlee1, Norafiza Mohd Yasin1, Sri Rahayu Sabtu2, Faidatul Syazlin Abdul Hamid1, Yuslina Mat Yusoff1, Ermi Neiza Mohd Sahid1, Azian Naila Md Noor1, Syahzuwan Hassan1, Nur Aisyah Aziz1, Ezalia Esa1

1Haematology Unit, Cancer Research Centre, Institute for Medical Research, National Institutes of Health, Setia Alam, Selangor; 2 Hospital Pakar Sultanah Fatimah, Muar, Johor

[email protected]

Background: Haemoglobin Köln is the most common unstable haemoglobin (Hb) variant involving the substitution of amino acid valine to methionine located at Codon 98 of the beta globin gene (HBB). It is reported in various ethnic backgrounds worldwide but rarely found in Malaysia. To the best of our knowledge, this was our second case of Hb Köln reported among Malays that presented with unexpectedly low SpO2 level with features of chronic haemolytic anaemia.

Case report: We report a 1 years-old Malay girl who was admitted for acute bronchiolitis with oxygen saturation of 88% under room air. She responded well with antibiotics and the symptoms subsided. However, oxygen saturation remained low at 91% under room air. There was no history of blood transfusion and no hepatosplenomegaly. Full blood count showed moderate anaemia with haemoglobin (Hb), MCV, MCH, RBC, RDW-CV and reticulocyte of 10.4g/dl, 86fL, 24.8pg, 4.20 106/μL, 16.5% and 8.96% respectively. Peripheral blood film (PBF) showed features of oxidative haemolysis with background of hypochromic microcytic red blood cells (RBC) with polychromasia, bite cells, keratocytes and spherocytes seen. G6PD status was normal. The biochemical tests were done to support the diagnosis of haemolysis. High performance liquid chromatography (HPLC) revealed high HbF level (17.5%), normal HbA2 with multiple small peaks at C window at RT 4.95s and 4.65s with the level of 3.7% and 1.3% respectively. Based on capillary electrophoresis (CE), the abnormal peak located at zone 4 (2.4%) with raised HbF level (18.5%). Further family history unravels; the older sibling and his father have similar symptoms and PBF features. In view of persistent low Spo2 level with abnormal PBF features, underlying methaemoglobinaemia or haemoglobin variant was suspected. Sanger sequencing of the HBB gene identified a heterozygous state of codon 98 [GTG>ATG] Haemoglobin Köln mutation.

Discussion & Conclusion: Hb Köln is the most common unstable Hb, classically presented with chronic haemolytic anaemia, but their clinical course is generally quite benign. This variant is often observed as a de novo mutation. Interestingly our case showed autosomal dominant inheritance pattern. This haemoglobin variant also led to unexpectedly low SpO2 level in asymptomatic cases as the result of methaemoglobinaemia produced by autoxidation of unstable hemoglobin variants. Molecular analysis is pivotal in providing information for the diagnosis and subsequently translated to clinical decision making, genetic counselling and family screening.


Ab

stract - C

S CR

Lab

ora

tory

CL9

MAST CELL LEUKEMIA

Annie Souti1, Nizmah Mahani Mokhri2, Tiffany Yap3, Nur Hidayah Muhammad Yasin4, Kimberly Fe Joibi5, Kathleen Zunica Jidokson6, Fenny Rozalia Dausy7, Laura Barintang8, Ahmad Nasirudin Mustafa9

1Department of Pathology, Hospital Queen Elizabeth, Kota Kinabalu, Sabah;2Hospital Wanita dan Kanak-kanak Sabah, Likas, Sabah

[email protected]

Background: Mast cell leukemia (MCL) is the leukemic manifestation of systemic mastocytosis (SM), and it is a very rare form of leukemia. It may be do novo or secondary to an underlying mastocytosis. MCL diagnosis requires the presence of SM criteria with additional features including leukemic infiltration in the bone marrow (BM) and/or blood by at least 20% abnormal mast cells. KIT D816V mutation is commonly found. Patient often present with symptoms of mast cell activation syndrome and this disease is known to be extremely aggressive with a grave prognosis.

Case report: We report a case of MCL in a 13-year-old boy, whom presented with 2 months history of recurrent urticaria, fever, rash over the trunk, and huge hepatosplenomegaly. His condition worsened and progressed to ascites, pleural effusion and pedal edema. Laboratory investigations showed mild anemia (Hb 9.9-11.4g/dL), leucocytosis (TWBC 40.5-78.3 x 103/uL), and thrombocytopenia (12-22 x 103/uL). Initial peripheral blood film showed presence of 20-32% blast and 60-69% moderate to large abnormal cells with dark-purple granulated cytoplasm, having bilobed and multilobed condensed nuclei. Bone marrow aspirate was not done as patient was not clinically fit for the procedure. Peripheral blood immunophenotyping was performed with BD FACS Canto II 8-colours flow cytometry using an extensive Acute Myeloid Leukemia panels, and analyzed with Cytonogs Infinicyt 2.0 software. The immunophenotyping showed presence of 9.7-14.7% myeloblast and 62.0-65.8% abnormal mast cells. These mast cells expressed CD45 intermediate, low to high SSC, CD117+(bright), CD11bdim, CD13+, CD33+, CD25+, CD123+, CD203+. They are negative for cyMPO, CD34, HLADR, other monocytic and lymphoid markers. Immunohistochemical staining of a cell block prepared from peripheral blood buffy coat using plasma-thrombin method also showed immunoreactivity to CD117 and CD25, with negative CD2 expression. Serum tryptase level was >200ug/L. Molecular study confirmed the presence of KIT D816V mutation. Management was initiated with corticosteroid and antihistamine (chlorphenamine, cimetidine) prior to induction chemotherapy protocol ADE (AML BFM 2004 Modified), with added Imatinib. Unfortunately, there was no clinical improvement despite the intensive treatment and patient eventually succumbed.

Discussion & Conclusion: The rarity of the condition poses great challenge to both pathologist and the clinician. High level of suspicion is required in order to prompt for extensive investigations and expedite molecular analysis for diagnostic confirmation. The mediator-related signs and symptoms had initially raised the suspicion of possible basophilic leukemia as the main differential diagnosis. The utilization of extensive immunophenotyping panel had made it possible to make a presumptive diagnosis of MCL while waiting for molecular study confirmation. Sadly, the available treatment options were limited and earlier studies showed that therapy usually fails. The reported median survival time of patient with MCL is less than 6 months.


Ab

stract - C

S CR

Lab

ora

tory

Ab

stract - C

S CR

Lab

ora

tory

CL10

PSEUDOTHROMBOCYTOSIS DUE TO RED CELL FRAGMENTATIONS IN A PREGNANT LADY WITH HBH DISEASE MASQUERADING AS MYELOPROLIFERATIVE NEOPLASMS: A CASE REPORT

Tan Jie En1, Chang Wei Xuan2, Lau Hui Bing2, Yong Kar Ying3

1Medical Department, Miri Hospital, Sarawak, Malaysia;’2Pathology Department, Miri Hospital, Sarawak, Malaysia;3Haematology Unit, Medical Department, Miri Hospital, Sarawak, Malaysia

[email protected]

Background: Modern automated blood analyser using different technologies such as electrical impedance, optical method and fluorescent flowcytometry have revolutionised haematology analysis providing rapid and precise measurement of high volume of blood samples, hence reducing the time and cost of blood examination. However, certain medical conditions can cause spuriously high platelet count (pseudothrombocytosis) as demonstrated in our case report.

Case report: We report a case of a 33-year-old pregnant lady gravida 2 para 1 with underlying non-transfusion dependent, Haemoglobin H disease who presented to the combined medical clinic at 20 weeks of gestation with persistent thrombocytosis. Her medical records showed platelet ranging from 616 to 1477 x 109/L since 2019. She was clinically well with no symptoms of hyperviscosity and bleeding tendency. Physical examination showed she was pale with mild splenomegaly. Her baseline haemoglobin level ranged from 7.7 to 9g/dL from past clinic visits. She was not iron-deficient, with serum ferritin of 1408 ng/ml and transferrin saturation of 36.5%. Full blood count with Sysmex XN1000 with impedance mode showed persistent high platelet counts of 2300 x 109/L, haemoglobin (Hb) 7.2g/dL (red blood cells (RBC) 4.19 x 1012/L, mean corpuscular volume (MCV) 55.4 fL, mean corpuscular haemoglobin (MCH) 17.2 pg) and white blood cells (WBC) of 14.53 x 109/L. Peripheral blood film showed marked anisopoikilocytosis with hypochromic microcytic RBCs and numerous fragmented RBCs. Manual calculation of platelet count was adequate at 70-80/ high power field with large platelet seen. It was concluded that she has pseudothrombocytosis secondary to fragmented red cells due to her underlying HbH disease. She was well throughout the pregnancy with normal fetal assessment.

Discussion & Conclusion: Red cell fragmentation is not infrequently associated with erroneously high platelet count giving rise to pseudothrombocytosis. Other conditions associated with pseudothrombocytosis are also seen in cryoglobulinemia, microangiopathic haemolysis, in the presence of fragmented leukocytes, lipid droplets and in samples with fungal or bacteria contaminations. Our case demonstrated microerythrocytes and fragmented red blood cells which were misinterpreted as platelets by the automated haematology analyser on the impedance mode. In such conditions, the platelet count should be confirmed by alternative methods such as manual counting on peripheral blood films or running the sample on automated blood analyser with optical or flowcytometry mode to avoid misdiagnosis and overtreatment.


Ab

stract - C

S CR

Lab

ora

tory

CL11

SYSTEMIC MASTOCYTOSIS IN A CASE OF ACUTE MYELOID LEUKEMIA ASSOCIATED WITH t(8;21)

Fatin Adlia Arifin1, Hana Shafinaz binti Jamaluddin1

1Department of Pathology, University of Malaya Medical Centre

[email protected]

Background: Systemic Mastocytosis Associated with Hematological Neoplasm (SM-AHN) is a variant of Systemic Mastocytosis. The associated hematological neoplasm is widely variable and reported cases of associated Myelodysplastic syndrome, Myelopoliferative neoplasm, Acute Myeloid Leukaemia and lymphoid neoplasms have been previously described. Nevertheless, this condition remains a rarity in this diagnostic field. We would like to present a case of systemic mastocytosis diagnosed concurrently with AML with t(8;21) encountered at our centre.

Case report: A 19 year old man presents with lethargy, palpitation and loss of weight for 2 months duration. He was pale, with no palpable hepatosplenomegaly or lymphadenopathy.He was noted to have pancytopaenia ( Hb:4.6, WBC:27.3, platelet: 26, blast:48%). Initial bone marrow study reveals infiltration of marrow by Acute Myeloid Leukaemia with blasts exhibiting following immunophenotyping properties (CD34het/CD117+/ MPO+/ CD13+/CD56+). Cytogenetic and molecular studies show t(8;21) with presence of RUNXI-RUNXIT1 fusion transcript. Patient is subjected to 2 cycles of induction chemotherapy due to molecular persistence of fusion transcript RUNX1-RUNX1T1 after 1st cycle of induction, followed by another 2 cycles of HIDAC consolidation chemotherapy. During end of therapy marrow assessment, we discovered the presence of mast cells aggregates (10-20 cells aggregates) at the intratrabecular and perivascular areas, occupying 10-15% of the total marrow spaces. These mast cells are positive for aberrant marker CD 2/CD30 and CD34/CD117 which indicate clonality. We have advised for KIT mutation study and serum tryptase level to be sent at another centre for confirmation as these tests are not offered at our centre. We performed a retrospective assessment at the diagnostic marrow examination and confirmed the persistent of an increased mast cells. Due to the background of hypercellular marrow and diffused blasts infiltration at diagnosis, the cells was masked and thus not captured on immunophenotyping and trephine assessment.

Discussion/ Conclusion: AML with t(8;21) carries a good prognosis and are sufficiently treated with standard chemotherapy, with good response rate and overall survival. However, concurrent diagnosis of systemic mastocytosis and KIT mutation will alter the prognosis of this AML subtype and thus patient usually requires intensified chemotherapy with subsequent allogenic HSCT to improve survival ability. However, this condition is often missed during diagnosis of AML as the symptoms are usually non specific and patient will usually presents with diarrhoea, urticaria and abdominal pain due to the mediator release. Therefore diagnosis are often missed by attending physician that were not suspecting. Diagnosis of systemic mastocytosis associated with hematological neoplasm require fulfilment of the diagnostic criteria of multifocal dense aggregates of mast cells infiltration in tissue biopsy, with clonality of mast cells proven with KIT D816V mutation and expression of aberrant marker CD25 with or without CD2 and elevation of tryptase level. However, the lack of CD25 IHC renders us for using another marker (CD30) for confirmation of aberrant phenotype of the mast cells. Echoing other studies and case reports on similar findings, concurrent systemic mastocytosis is often missed during initial biopsy due to the hypercellularity of marrow during diagnosis and this disease is often picked up during follow up marrow analysis. Therefore, it is pertinent for attending pathologist to be vigilant and explore all possibilities which may further refine the definitive diagnosis.


Ab

stract - C

S CR

Lab

ora

tory

Ab

stract - C

S CR

Lab

ora

tory

CL12

UNUSUAL CASES OF HAEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (HLH) COMPLICATING APLASTIC ANAEMIA (AA), A POSSIBLE ASSOCIATION?

Weng Yan Sabrina Chee, Hana Jamaluddin, Mardziah Mohamad

Haematology Unit, Department of Pathology, University Malaya Medical Centre

[email protected]

Background: Haemophagocytic Lymphohistiocytosis (HLH) and Aplastic Anaemia (AA) represent two distinct disease entities, but they may have similar immune-mediated pathological aspects involving the activation of T-lymphocytes. The diagnosis of HLH is difficult unless there is suspicion and often masquerades as infection. However, it has been reported to cause bone marrow aplasia if left untreated. Cases with simultaneous occurrence of both conditions although rare, have also been reported.

Case series: We present our experience with two similar cases from a wide spectrum of age. The first patient is a 14 years old boy who presented with easy bruising and symptomatic anaemia for one month, complicated with an acute intracranial bleed. Bone marrow examination performed for the investigation of pancytopenia showed hypoplastic marrow with abnormal haemophagocytic activity. Clinical improvement was observed with the commencement of steroids. The second patient is a 65 year old man who was diagnosed with severe aplastic anaemia when he presented with pancytopenia and neutropenic sepsis. No evidence of HLH noted at the initial diagnostic marrow. He responded to Cyclosporin and Elthrombopeg initially, however losing response with worsening cytopenias two years later. A repeat bone marrow examination showed evidence of abnormal haemophagocytic activity in a hypoplastic marrow. Cytogenetic analysis revealed monosomy 7 which have been reported in 4-10% cases of AA which is associated with a more aggressive clinical course. Patient was started on steroids with transient improvement before succumbing to severe neutropenic sepsis. Both our patients exhibit hyperferritinaemia with low fibrinogen without clinical hepatosplenomegaly or positive family history of congenital HLH. The cause of secondary HLH was not apparent in both patients.

Discussion & Conclusion: Cases of AA associated with HLH were rarely reported. Both cases illustrate the importance of a high index of suspicion during diagnostic evaluation as the condition is potentially lethal if treatment is delayed.


Ab

stract - C

S CR

Lab

ora

tory

www.mshaema.com


V i r t u a l C o n f e r e n c eV i r t u a l C o n f e r e n c eth


souvenir programme

Documents