Il trapianto allogenico: quando e per chi? Daniela Cilloni (Torino)
Number of allogeneic HCTs for MDS paAents 65 years of age in the United States, 2005-2012.
Biology of blood and marrow transplanta3on 2017
HSCT in MDS : for whom, when and how? • SelecAon of paAents • Type of transplant (HSC source) • Treatment before transplant • InducAon regimens/intensity • Timing of transplant
For whom? • Intermediate 2 and high IPSS risk • Intermediate, high and very high R-IPSS • Therapy related MDS • High transfusion requirement
2015
HematopoieAc cell transplantaAon (HCT)- specific comorbidity index Blood 2005;106:2912-9
Comorbidity and Disease Status–Based Risk StraAficaAon of Outcomes Among PaAents With AML or MDS Receiving Allogeneic HematopoieAc Cell TransplantaAon J Clin Oncol 2007;25:4246-54
Effect of comorbidity on survival of MDS paAents Overall Survival Risk of Non-Leukemic Death Blood 2007;110:#2453
AML HSCT: URD, Sibling Donor, and UCB Survival Minnesota, Paris, and Nantes Peffault de la Tour, 2013
What about low/intermediate-1 IPSS? • Life expectancy of paAents with Intermediate-1 or low IPSS risk at diagnosis was higher when transplanaAon was delayed but performed before progression to AML. Cutler et al., Blood 2004; 104:579-585
No SCT SCT
Low and Intermediate-1 risk IPSS pa5ents survival benefit of the nontransplantaAon strategy in low/intermediate-1 IPSS MDS Adapted from Koreth et al. JCO 2013
Intermediate-2 and high risk IPSS pa5ents survival benefit of the early RIC transplantaAon strategy in intermediate-2 and high risk IPSS MDS Adapted from Koreth et al. JCO 2013
When? Timing of transplantation � immediate transplantation for Int-2/high-risk pts � delayed transplantation for Int1/low risk pts until progression ( but before transformation to AML)
Early HSCT is associated with improved outcome Bone marrow transplantation from HLA-identical siblings as first-line treatment in patients with myelodysplastic syndromes: early transplantation is associated with improved outcome 100 V Runde 1 , T de Witte 2 , R Arnold 3 , A Gratwohl 4 , J Hermans 5 , A van Biezen 5 , D Niederwieser 6 , M Labopin 7 , MP Walter-Noel 8 , A Bacigalupo 9 , N Jacobsen 10 , P Ljungman 11 , E Carreras 12 , HJ Kolb 13 , C Aul 14 and J Apperley 15 on behalf of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT) ´, University Hospital of Essen, Germany; University Hospital St Radboud, Nijmegen, The Netherlands; University Hospital Charite 75 <4 mon t hs ( n = 36 ) Surv i va l 50 >12 mon t hs ( n = 39 ) 4 – 12 mon t hs ( n = 53 ) 25 P = 0 . 03 0 0 12 24 36 48 60 Mon t hs Bone Marrow Transplanta3on 1998
HSCT in MDS : for whom, when and how? • SelecAon of paAents • Type of transplant (HSC source) • Treatment before transplant • InducAon regimens/intensity • Timing of transplant
Stem cell source (PBSC or BM?) PBSC compared to BM as SC source : • faster engraftment • more cGVHD • lower NRM • better 2-yrs EFS Guardiola et al., Blood 2002 Maris et al. Blood 2003 Deeg et al., Blood 2002
Stem cell donor • match related donor (MRD) • match unrelated donor (MUD) 8/8 • match unrelated donor (MUD) 7/8 • Alterna5ve donors? • Cord blood • HaploidenAcal donor
Adjusted probability of transplant-related mortality in adult MDS paAents by donor source. MUD= match unrelated donor Blood 2013;122:1974 MRD= match related donor
Adjusted probability of relapse in adult MDS paAents by donor source MUD= match unrelated donor Blood 2013;122:1974 MRD= match related donor
Adjusted probability of DFS in 694 adult MDS paAents by donor source. MUD= match unrelated donor Blood 2013;122:1974 MRD= match related donor
Adjusted probability of overall survival in 701 adult MDS paAents by donor source. MUD= match unrelated donor Blood 2013;122:1974 MRD= match related donor
Bone Marrow TransplantaAon (2013), 1–6
American Journal of Hematology 2017
Pre transplant induc5on therapy: really needed? • Chemotherapy for those with high blast count ?(>10%) • Hypomethylating agents before transplant ?
Hypomethylating agents and transplant Patients who discontinue 5AC for various reasons have a median survival of only 5.6 months When 5AC is discontinued because of progressive disease the median survival is 17 months even after HSCT In the study by Prébet et al the median survival was not reached in patients transplanted with stable disease at the time when 5AC was stopped CONCLUSION : for patients who are transplant candidates HCT should be considered while still responding to hypomethylating therapy
Pretransplantation Induction Chemotherapy and Posttransplantation Relapse in Patients with Advanced Myelodysplastic Syndrome Bart L. Scott, 1,2 Barry Storer, 1,2 Michael R. Loken, 3 Rainer Storb, 1,2 Frederick R. Appelbaum, 1,2 H. Joachim Deeg 1,2 1 Fred Hutchinson Cancer Research Center; 2 University of Washington School of Medicine; and 3 Hematologics Inc., Seattle, Washington 32 S-AML 24 CHT 8 no CHT 93 RAEB/RAEB-T 125 MDS pa5ents 9 CHT 33 chemotherapy 62 no CHT 92 no chemotherapy . Biology of Blood and Marrow TransplantaAon 11:65-73 (2005)
Pretransplantation Induction Chemotherapy and Posttransplantation Relapse in Patients with Advanced Myelodysplastic Syndrome Bart L. Scott, 1,2 Barry Storer, 1,2 Michael R. Loken, 3 Rainer Storb, 1,2 Frederick R. Appelbaum, 1,2 H. Joachim Deeg 1,2 1 Fred Hutchinson Cancer Research Center; 2 University of Washington School of Medicine; and 3 Hematologics Inc., Seattle, Washington 32 S-AML 24 CHT 8 no CHT 93 RAEB/RAEB-T 125 MDS pa5ents 9 CHT 33 chemtorapy 62 no CHT 92 no chemotherapy . Biology of Blood and Marrow TransplantaAon 11:65-73 (2005)
Damaj et al. Biol Blood and Marrow Transpl 2014
5-Azacitidine for myelodysplasia before allogeneic hematopoietic cell transplantation T Field 1 , J Perkins 1 , Y Huang 2 , MA Kharfan-Dabaja 1 , M Alsina 1 , E Ayala 1 , HF Fernandez 1 , W Janssen 1 , J Lancet 3 , L Perez 1 , D Sullivan 1 , A List 3 and C Anasetti 1 1 1 0.9 0.9 Relapse-free Survival 54 paAents 0.8 0.8 Overall Survival 30 AZA 0.7 0.7 0.6 0.6 24 no AZA 0.5 0.5 0.4 0.4 0.3 0.3 p -value = 0.25 p -value = 0.30 0.2 0.2 Vidaza = N Vidaza = N 0.1 0.1 Vidaza = Y Vidaza = Y 0 0 0 200 400 600 800 1000 1200 0 200 400 600 800 1000 1200 Days Days 1 1 Cumulative Incidence of Vidaza = N 0.9 0.9 Cumulative Incidence Vidaza = N non-relapse Mortality Vidaza = Y 0.8 0.8 Vidaza = Y p -value = 0.16 0.7 p -value = 0.66 0.7 of Relapse 0.6 0.6 0.5 0.5 0.4 0.4 0.3 0.3 0.2 0.2 0.1 0.1 0 0 0 200 400 600 800 1000 1200 0 200 400 600 800 1000 1200 Days Days Bone Marrow Transplanta3on (2010) 45, 255–260
Multicenter study evaluating the impact of hypomethylating agents as bridging therapy to hematopoietic stem cell transplantation in myelodysplastic syndromes A B 109 paAents 81 HMA 28 no HMA A B Kim et al . Int J Hemtol 2014
OS and RFS according to HMA treatment group C D E F Kim et al . Int J Hemtol 2014
Azaci5dine vs induc5on chemotherapy before HSCT: SeaSle retrospec5ve data in 68 pa5ents (35 pts AZA, 33 IC) Gerds A.T.et al. Biol Blood Marrow Transpl. 2012
Biol Blood Marrow Transplant 22 (2016)
Biology of Blood and Marrow Transplantation journal homepage: www.bbmt.org 2014 Cytogenetics, Donor Type, and Use of Hypomethylating Agents in Myelodysplastic Syndrome with Allogeneic Stem Cell Transplantation Betul Oran 1 , * , Piyanuch Kongtim 1 , Uday Popat 1 , Marcos de Lima 1 , Elias Jabbour 2 , Xinyan Lu 3 , Julien Chen 1 , Gabriella Rondon 1 , Partow Kebriaei 1 , Sairah Ahmed 1 , Borje Andersson 1 , Amin Alousi 1 , Stefan Ciurea 1 , Elizabeth Shpall 1 , Richard E. Champlin 1 256 MDS paAents at the MD Anderson Cancer Centres 40 (15.6%) chemotherapy 122 ( 47.7%) HMA 16 (6.2%) Chemo+HMA
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