Comparison of Outcomes for Non-Myeloablative (NMA) and Myeloablative (MA) Conditioning for Adults with Acute Lymphoblastic Leukaemia (ALL) in First and Second Complete Remission (CR): a Center for International Blood and Marrow Transplant Research (CIBMTR) Analyisis.
Authors: Marks David I. , Wang Tao , Peréz Waleska S. , Bunjes Donald W. , DiPersio John F. , Tallman Martin S. , Weisdorf Daniel J. 
Published: October 2019

Abstract
Abstract 872
The efficacy of reduced intensity or NMA conditioning for allogeneic hematopoietic stem cell transplantation (HCT) for adults with ALL is uncertain. Using CIBMTR data we compared the outcomes of 92 patients ≥16 years who had NMA conditioning with 1421 patients who had myeloablative conditioning (MC) for allografts using sibling and unrelated donors for ALL in CR1 or CR2. Conditioning in the NMA group included regimens containing busulfan ≤ 9 mg/kg (27), melphalan ≤ 150 mg/m2 (23) or low-dose total body irradiation (36) and others (7). The NMA conditioning group were older (median 45 vs. 28 years, p<0.001) and more received peripheral blood grafts (73% vs. 43%, p<0.001). Other major potential prognostic factors were similar in the two groups. After a median follow-up of 54 vs. 38 months respectively, the NMA vs. MA conditioning groups had slightly less acute grade 2-4 graft-vs-host-disease (GVHD), less chronic GVHD but similar transplant-related mortality (TRM). However the NMA conditioning group experienced slightly more relapse (35% vs. 26%, p=0.08) yet similar overall survival (OS) (Figure): Outcome:MANMAP-value Acute GVHD @ 100 days, grades (2-4)46 (43-49)39 (29-49)0.16 Chronic GVHD @ 3 years42 (39-44)34 (24-44)0.16 TRM @ 3 years, %33 (31-36)32 (23-43)0.86 Relapse @ 3 years, %26 (23-38)35 (25-46)0.08 Leukemia-free survival (LFS) @ 3 years, %41 (38-44)32 (22-43)0.12 OS @ 3 years, %43 (40-46)38 (28-49)0.39
Multivariate analysis showed that a low Karnofsky score (KPS) and T cell depletion were associated with higher TRM but conditioning intensity had no impact on TRM (RR with NMA 0.97, P=0.89). Relapse risk with NMA conditioning was slightly, but not significantly higher ( (RR)=1.34, p=0.15) as was a CR2, particularly with a short (<12 months) initial CR (RR=2.74; longer remission (12 months) RR1.51, P<0.0001). Multivariate analysis demonstrated significantly improved OS with: KPS>80, CR1, lower WBC, no extramedullary disease, a well matched unrelated or a sibling donor, transplant since 2001, in younger patients (<30y), conditioning without TBI and GVHD prophylaxis without T-cell depletion. However ATG use did not affect survival.. The most common cause of death was relapse; which was similar in MA and NMA HCT (46% vs. 35%). Despite the older age in the NMA group, OS and LFS at 3 years was similar to those receiving MA HCT. In comparing the outcomes of NMA and MA conditioning in sibling vs. unrelated donor transplant recipients we found that there was slightly, but not significantly more relapse with NMA [34 (18-52)% vs. 26 (23-30)%, p=NS and 36 (24-49)% vs. 25 (22-28)%, p=NS respectively]. This was associated with similar OS of 40 (23-59)% vs. 50 (45-54)% and 37 (25-50) vs. 38 (34-41)% in the sibling and unrelated donor groups.

Conclusions:
These data suggest that NMA conditioning is worthy of investigation in prospective clinical trials of adult ALL. These trials should include both well matched unrelated and related donors, but importantly, NMA conditioning may not fully overcome the adverse impact of poor pre-HCT KPS on outcome.

>Disclosures:
No relevant conflicts of interest to declare.