Hematopoietic Stem Cell Transplantation of Acute Lymphoblastic Leukemia

in TaiwanTran-Der Tan, Chair of Hematopoietic Stem Cell Transplantation Multidisciplinary Team, Koo Foundation Sun Yat-Sen Cancer Center, Taipei.

On Behalf of Taiwan Society of Blood and Marrow Transplantation (TSBMT)

I have no personal or financial interests to declare:

I have no financial support from an industry source at the current presentation.

Honorarium speaker of Amgen, Celgene, Janssen, Roche, and BMS.

대한혈액학회 Korean Society of Hematology

COI disclosureName of author ： Tran-Der Tan

Case 1

• 49-yearold woman hair stylist, acute lymphoblastic leukemia diagnosed in Mar 2015 in the presentation of fever, malaise, easy fatigue, and abdomen fullness, and then anemia and hyperleukocytosis WBC 270000/ul found, underwent Imatinib and then Dasatinib plus dexamthasone with complete remission achieved, however, she declined to undergo more intensive chemotherapy or allo-transplant at outside hospital.

• 6 months later leukemia relapsed and then try nilotinib with temporary remission, ie. triple TKIs failured then went to our hospital and CHR achieved after phase I GMALL induction chemotherapy then MMR achieved after phase II, s/p conditioning regimen TBI/Cy + ATG and stem cell infusion on 2016/01/29 and now post-transplant +2Y11M.

Case 2

• 44-year-old worker, Pre-B cell Acute lymphoblastic leukemia with normal cytogenetic and no specific gene mutation found, in the presentation of abdomen pain and hepatosplenomegaly found in late Mar 2018 and then went to prior hospital and then diagnosis made and anemia and thrombocytopenia found as well with WBC 53000/ul, Hgb 7.7gm/dl, and platelet 9000/ul; with packed cell and platelet transfusion, then 1st cycle of HyperCVAD chemotherapy started with CR achieved, followed by subsequent Hyper-CVAD/MA for totally 6 cycles at our hospital then prepared for allogeneic hematopoietic stem cell transplant.

• Continued CR with MRD(+) found in Sep 2018, just before the start of transplant, s/p blinatumumab with CR with MRD negative achieved in Oct 2018.

• s/p Haploidentical allogeneic stem cell transplantation from his daughter on Nov 13, 2018 with TBI 12Gy/Flu + PTCY conditioning and now post-transplant +121 days.

Incidence of myeloid malignancy in Taiwan, 2016

AML ALL CML, bcr-abl (+) CLL AML, Undifferentiated MPN MDS Others

Incidence of ALL in Taiwan, 2016

Incidence of cancer and mortality in Taiwan, 2016

Introduction

• This is a retrospective study with data base from registry of Taiwan Society of Blood and Marrow Transplantation (TSBMT).

• We want to know the real world outcome of patients of acute lymphoblastic leukemia whom underwent (allogeneic) hematopoietic stem cell transplantation after induction chemotherapy.esi

• Besides, after the introduction of targeted tyrosine kinase inhibitor and allogeneic hematopoietic stem cell transplantation the overall survival improved in historical comparison in Ph(+) ALL. We campared the outcome of Ph(+) versus Ph(-) patients.

• For relapsed patients, salvage chemotherapy could achieve less patients in remission and then 2nd transplant is an option for limited patients and we will see the overall survival.

Indcution therapy – pediatric inspired protocol

• GMALL protocol

• GRAALL protocol

• MDACC protocol, HyperCVAD/MA

• TPOG protocol

• *Tyrosine kinase inhibitor (imatinib or dasatinib) added if Ph(+).• **Rituximab added if CD20+.

Intensive consolidation therapy

• Allogeneic hematopoietic stem cell transplantation, with either myeloablative TBI/Cy, BUCY, FluBu4, or FluBu2, FluCy, or other RIC coditioning regimen as long as remission achieved for high risk patients.

• Autologous hematopoietic stem cell transplantation, with either TBI/Cy or BUCY conditioning regimen if complete remission achieved.

• Non-transplant regimen, to complete the various chemotherapy protocol.

Definition of high risk group

• > 30 yrs of age• WBC count > 30K in B-ALL, > 100K in T-ALL• Ph+ — t(9;22), BCR-ABL translocation• Ph-like lesions• Other chromosomal aberrations

• t(4;11), 11q23+, MLL rearrangement• Hypodiploidy (≤ 44 chromosomes)

• CNS involvement • MRD positive (> 10-4 or 0.01%) after induction

Total Patients Number Received Transplant = 526

Total Patients Number Received 2nd Transplant = 50

Histocompatability and Source of Stem Cells

26 patients received both bone marrow and peripheral blood stem cells.

Overall Survival of Total 526 Patients

Ph(+) versus other ALL Disease Status before HSCTTable 3. Ph(+) and Disease status

Total Alive Dead

All patients 526 281 245

BCR/ABL(+) subtotal 93 (100%) 56 37

CR1 77 (83%) 53 24

CR2 9 (10%) 2 7

CR3 1 (1%) . 1

induction failure 1 (1%) . 1

relapse 5 (5%) 1 4

Others subtotal 433 (100%) 225 208

CR1 218 (50%) 145 73

CR2 107 (25%) 48 59

CR3 18 (4%) 5 13

Unknown 7 (2%) 4 3

induction failure 28 (6%) 6 22

relapse 55 (13%) 17 38

Ph(+) vs other ALL

Overall Survival of different Disease Status before Transplant

Overall Survival of Patients received 2nd Transplant

Cause of Death

Relapse/progressive disease Infection GVHD

Unknown New malignancy VOD/SOS

Idiopathic pneumonitis Hemorrhage Rejection/graft failure

Cardiac toxicity Pulmonary toxicity Others

Take home message1. 294 ALL occurred in Taiwan in 2016, around 12~15% of all

myloid malignancies (AML, ALL, MDS, MPN); bimodal distribution in male but not in female.

2. Allo-HSCT for high risk patients and Auto-HSCT for limited patients after a variety of induction chemotherapy protocol.

3. Better outcome in CR1 > CR2 > induction failure and relapsed/refrctory.

4. No significant difference of survival between Ph(+) versus Ph(-), ie. Targeted therapy plus allo-HSCT can overcome the poor prognostic factor Ph(+).

5. Durable survival is worse but still to be considered for second transplant

• THANK YOU FOR YOUR LISTENING