bone marrow transplant in paediatric haematology rob wynn consultant paediatric haematologist...
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Bone marrow Transplant in Paediatric Haematology
Rob Wynn
Consultant Paediatric Haematologist
Director Paediatric BMT Programme
Understanding BMT
• Two competing immune systems– Donor vs Recipient
• Recipient wins– Rejection– Relapse– Transplant fails
• Donor wins– Graft versus host disease– Remission of malignant disease– Transplant is a succes
Donor immunity recipient immunity
Supporting engraftment
• Recipient ablation
Donor bone marrow
Myeloablative chemo-radiotherapy
Time after BMT
Indications for HSCT
• Malignant diseases– Chronic leukaemias– Acute leukaemias – Myelodysplasia– Myeloma– Lymphoma
• Mode of Action of SCT in Malignant Disease– Graft versus Leukaemia– Intensity of Conditioning Therapy
Non malignant indications for BMT
• Haematological Indications– Disorders of HSC number – aplastic
anaemia, Fanconi anaemia– Red cell disorders – thalassaemia, sickle cell
anaemia, Diamond Blackfan Anaemia– White cell disorders – congenital
neutropenia, Schwachman Diamond– Lymphocyte disorders – immunodeficiency
(SCID), Haemophagocytic syndromes– Platelet disorders – Glanzmann’s
Non malignant indications for BMT
• Non haematological indications for HSCT
– Enzyme deficiency• Mucopolysaccharide disorders (MPS)• Adrenoleucodystrophy
– Disorders of Osteoclast function• Malignant Infantile Osteopetrosis (MIOP)
– Others (experimental)• Osteogenesis imperfecta (delivering MSC)
– Autoimmune disorders (delivering IS, resetting IS)• Systemic sclerosis,
Sources of HSC• Sibling
– 1:4 chance of matching where same parents• Other family members
– Only where consanguinity• Haplo-identical
– Parent, when desperate and need it quickly• Matched Unrelated Donor
– From donor registry– Largely caucasian donors– Unrelated UCB donor pools reflect ethnic mix of population better
• Autologous– Use and freeze patients own cells– +/- purging
Sources of stem cells
• Bone marrrow– Perhaps 1% of marrow MNC are CD34+
• Umbilical cord blood – Perhaps 1% of CB MNC are CD34+
• Mobilised peripheral blood– Can mobilise vast quantities of CD34+ cells– G-CSF to recipient– Leukapheresis of MNC fraction
Outcomes
• This is a risk balance question• Risk of disease
– Natural history etc• Risk of Transplant
– How well is the patient?– How well matched is the donor?
• Consent will include risk of death or serious morbidity balance against risk of no transplant
• Process and consent in transplant is more surgical than medical in type
Complications of transplant (1)
• Complications of High Dose chemotherapy– Acute
• Mucositis• Liver – VOD – weight gain, jaundice,
hepatomegaly
– Chronic• Infertility• Growth • Second malignancy
Complications of Transplant (2)
• Infection– Early – Neutropenic
• Bacterial – prophylaxis and treatment• Fungal – prophylaxis and treatment
– Late • Viral• Usually fatal infection is preceded by period of
asymptomatic viraemia• Screening – PCR – of blood urine stool weekly so as to
intervene with antivirals in this window period• Adenovirus, CMV, EBV
Complications of Transplant (3)
• Graft versus Host Disease• With HLA mismatch• Donor T cells against recipient tissue antigens
– Acute• SKIN, GUT, LIVER• Grade 0 - IV
– Chronic• ALL ORGANS (except brain)
• Will include Graft Versus Tumour• Prophylaxis with match and ciclosporin• Treat with steroids and other immune suppression