Similar outcomes using myeloablative vs reduced-intensity allogeneic transplant preparative regimens for AML or MDS

Abstract

Although reduced intensity (RIC) and nonmyeloablative (NMA) conditioning regimens have been used for over a decade, their relative efficacy versus myeloablative (MA) approaches to allogeneic hematopoietic cell transplantation (HCT) in patients with acute myelogenous leukemia (AML) and myelodysplasia (MDS) is unknown. We compared disease status, donor, graft and recipient characteristics with outcomes of 3731 MA with 1448 RIC/NMA procedures performed at 217 centers between 1997 and 2004. Five year univariate probabilities and multivariate relative risk (RR) outcomes of relapse, transplant related mortality (TRM), disease free survival (DFS) and overall survival (OS) are reported. Adjusted OS at 5 years was 34%, 33%, and 26% for MA, RIC and NMA transplants, respectively. NMA conditioning resulted in inferior DFS and OS but there was no difference in DFS and OS between RIC and MA regimens. Late TRM negates early decreases in toxicity with RIC and NMA regimens. Our data suggest higher regimen intensity may contribute to optimal survival in patients with AML/MDS, suggesting roles for both regimen intensity and graft vs. leukemia in these diseases. Prospective studies comparing regimens are needed to confirm this finding and determine the optimal approach to patients who are eligible for either MA or RIC/NMA conditioning.

Outcome of conditioning intensity in acute myeloid leukemia with monosomal karyotype in patients over 45 year‐old: A study from the acute leukemia working party (ALWP) of the European group of blood and marrow transplantation (EBMT)

“…It is then not surprising that even with age being significantly higher in the RIC group, this was not translated into worse outcomes. Other retrospective studies comparing RIC with MAC in AML have shown similar DFS and OS as in our analysis, but the increased relapse incidence usually associated with RIC was not found in the present report [16,30]. We also found that in-vivo T-cell depletion with ATG was not associated with an increased risk of relapse as it has been recently described [31].…”

“…Cytogenetics affects similarly RIC and MAC with increased NRM and relapse incidence [30]. In our cohort restricted to very bad-risk leukemia, we observed a reasonable long-term survival, with a relapse incidence of 50%.…”

Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European group for blood and marrow transplantation

“…This study also identified poor risk cytogenetics, being in second versus in first CR, and conditioning with low-dose TBI-based RIC as being associated with worse LFS or OS, confirming previous reports. 18,31,32 Finally, our study demonstrated higher mortality in patients above 56 years of age at transplantation in comparison with younger patients, in contrast to what has been observed in a recent report from the CIBMTR analyzing data from 545 patients with AML given RIC allo-SCT, 18 perhaps because analyses were not adjusted for comorbidities at transplantation (more likely to be more frequent in older patients) in current study.…”

The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach

“…(86)(87)(88)(89)(90)(91)(92)(93)(94)(95). During the prospective German-Austrian study (76), a growing number of patients received RIC-regimens.…”