Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) for Patients with Acute Myeloid Leukemia (AML): Long Term Results of a “Donor” Versus “No Donor” Comparison.
Authors: Mohty Mohamad , de Lavallade Hugues , El-Cheikh Jean , Ladaique Patrick , Faucher Catherine , Furst Sabine , Vey Norbert , Coso Diane , Stoppa Anne-Marie , Gastaut Jean-Albert , Chabannon Christian , Blaise Didier 
Published: October 2019

Abstract
RIC regimens have emerged as an attractive modality to decrease transplant-related toxicity (TRM). However, the potential higher relapse rate after RIC allo-SCT is still under considerable debate. This report describes the long term results of 95 consecutive AML patients, diagnosed between Nov. 1999 and Dec. 2003 in a single institution, and who were considered as potential candidates for RIC-allo-SCT. Using a genetic randomization through a “donor” versus “no donor” comparison, the aim was to assess the real benefit of RIC-allo-SCT for adult AML and its impact on outcome. In this series, 35 patients (37%; “donor” group) had an “identified” HLA-identical sibling donor, while the remaining 60 patients had no HLA-matched related donor (“no donor” group). As per institutional policy, HLA-matched unrelated donors were not considered during the study period. No significant differences in patients or AML features were found between the two groups. In the “donor” group, 25 patients (71%; median age, 51 (range, 26–60)) could actually proceed to the RIC-allo-SCT. The 10 remaining patients with an identified donor did not receive allo-SCT because of early relapse after CR (n=2), patient or donor refusal (n=6), and psychiatric disorders appearing before allo-SCT (n=2). The current median follow-up is 60 months. In an “intention-to-treat” analysis, the KM estimate of leukemia-free survival (LFS) was significantly higher in the “donor” group as compared to the “no donor” group (P=0.003; 60% versus 23% at 7 years). When restricting the analysis to patients who could actually receive the RIC-allo-SCT (median follow-up, 40 months from time of allo-SCT), the difference in LFS was also significant between this group of 25 patients (“transplant” group) and the remaining 70 patients (“no transplant” group) who did not receive allo-SCT (P=0.0002; 72% versus 24% at 7 years). In the “transplant” group, RIC-allo-SCT was performed at a median of 209 (range, 119–413) days after diagnosis. No major toxicities were encountered during RIC administration (fludarabine, busulfan and ATG), and only 3 patients died from TRM, for a cumulative incidence of 12% (95%CI, 3–32%) at last follow-up. This relatively low TRM translated towards a significantly higher overall survival (OS) in the “transplant” group as compared to the “no transplant” group (P=0.0003). In the “intention-to-treat” analysis, OS was still significantly higher in the “donor” group as compared to the “no donor” group (P=0.003; Figure below). After controlling for relevant factors, in the multivariate analysis, only actual performance of RIC-allo-SCT (P=0.0005; RR=4.1; 95%CI, 1.8–9.1), was significantly predictive of an improved LFS, further confirming the overall benefit of RIC-allo-SCT for adult AML patients. We conclude that if a matched related donor is identified, RIC-allo-SCT should be proposed since it represents a valid and potentially curative option for AML patients not eligible for standard myeloablative allo-SCT.
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