Optimizing the Timing of Allogeneic Blood or Marrow Transplantation (BMT) in a Prospective Cohort of Relapsed or Refractory Acute Myeloid Leukemia (AML)
Authors: Liu Hong , Zhang Yali , Hahn Theresa , Thomas Julie , Wetzler Meir , Wang Eunice S. , Hernandez Lise , Ross Maureen , Chen George L. , McCarthy Philip L. 
Published: October 2019

Abstract
Abstract 3096
Relapsed or refractory AML is difficult to treat even with allogeneic BMT. In an attempt to reduce leukemia burden and limit toxicities from multiple re-induction attempts, we initiated a treatment strategy to offer allogeneic BMT prior to count recovery, within 3 to 4 weeks after re-induction. Among 156 consecutive AML patients referred to our BMT program between 01/2003 and 03/2008, 84 (54%) patients did not receive an allogeneic BMT due to: death (n=25, 30%), patient refusal (n=13, 16%), disease progression (n=13, 16%), autologous BMT (n=11, 13%) and other (n= 22, 26%). Seventy-two (46%) patients received an allogeneic BMT: 21 (29%) patients were prospectively identified with very high risk features (primary induction failure (PIF) or refractory relapse (RR)) and received re-induction with the intent-to-induce hypoplasia and transplant prior to count recovery. The remaining 51 patients received re-induction with the goal of inducing complete remission (CR) prior to BMT (the intent-to-induce remission group). Patient and BMT-related characteristics, as well as BMT outcomes are summarized in Table 1. Patients were prospectively accrued to myeloablative or reduced intensity BMT protocols depending on their age, KPS, co-morbidities, disease risk and the degree of HLA match. The intent-to-induce hypoplasia group had a lower 2-year PFS and OS (reflecting their very high risk disease characteristics). In subgroup analysis in patients with PIF or RR, there was no difference in 2-year PFS (15% vs. 22%, p=0.39) or 2-year OS (20% vs. 33%, p=0.32) between the intent-to-induce hypoplasia and the intent-to-induce remission groups. The overall and day 100 TRM was similar in both groups of patients with PIF or RR. Using this prospective strategy of identifying patients with very high risk disease with the intent to transplant them during hypoplasia after re-induction therapy, 46% of all the referred AML patients were able to undergo allogeneic BMT. This is higher than other published series where < 30% of patients proceeded to transplant where the goal of re-induction was to induce and achieve CR prior to transplant. Our data show that it is safe to transplant advanced AML patients early (within 3 to 4 weeks) after re-induction with acceptable mortality in patients with very high risk AML who otherwise might not be transplant candidates.Table.Patient Characteristics and OutcomesFactorIntent-to-induce remission (N=51)Intent-to-induce hypoplasia (N=21)PN(%)N(%)Patient and Disease CharacteristicsAge at BMT18-4016 (31)4 (19)NS41-6028 (55)13 (62)61+7 (14)4 (19)KPS at BMT≥9023 (45)1 (5)<0.01≤8028 (55)20 (95)WBC at diagnosis≥30 x 109/L12 (24)9 (43)NS<30 x 109/L39 (76)12 (57)Cytogenetics at diagnosisFavorable2 (4)1 (5)NSIntermediate25 (49)14 (67)Adverse24 (47)6 (29)De novo vs. Secondary AMLDe novo39 (76)17 (81)NSSecondary12 (24)4 (19)Disease status at BMTFirst CR38 (75)0 (0)<0.01Second or greater CR4 (8)1 (5)PIF/RR9 (18)20 (95)BMT-Related CharacteristicsDonor sourceRelated24 (47)8 (38)NSUnrelated27 (53)13 (62)Stem cell typeBM±PB10 (20)1 (5)NSPB41 (80)20 (95)HLA 10/10 matchMatched46 (90)16 (76)NSMismatched5 (10)5 (24)Gender matchMatched30 (59)13 (62)NSMismatched21 (41)8 (38)Myeloablative conditioningCT±V15 (29)0 (0)<0.01BuCy5 (10)1 (5)Reduced intensity conditioningFluMel27 (53)15 (71)<0.01FluCy4 (8)5 (24)Prior BMTPrior auto BMT2 (4)3 (14)NSNo prior auto BMT49 (96)18 (86)BMT-Related Outcomes2-yr PFS53%18%<0.0012-yr OS56%23%<0.001Day 100 TRM10%33%0.03NS: not significant, P>0.1

Disclosures:
Hahn: Novartis: stock.