Reduced Intensity Conditioning (RIC) Allogeneic Stem Cell Transplantation (allo-SCT) for Patients with Acute Myeloid Leukemia (AML): A Donor Versus No Donor Comparison.
Authors: Mohty Mohamad , de Lavallade Hugues , Ladaique Patrick , Faucher Catherine , Vey Norbert , Coso Diane , Stoppa Anne-Marie , Gastaut Jean-Albert , Blaise Didier 
Published: April 2020

Abstract
Standard myeloablative allo-SCT is an established therapy for adult patients with AML. However, because of the high incidence of TRM, this procedure is often limited to younger patients. RIC regimens allow decreasing transplant-related toxicity. No randomized studies between RIC-allo-SCT for AML and chemotherapy alone are yet available. This report describes 95 consecutive AML patients from a single institution, who were considered as potential candidates for RIC-allo-SCT. Using a genetic randomization through a "donor" vs. "no donor" comparison, the aim of this analysis was to assess the real benefit of RIC-allo-SCT for adult AML. In this study, 35 patients (37%; "donor" group) had an "identified" HLA-identical sibling donor, while 60 had no related donor ("no donor" group). No significant differences in patients or AML features were found between the 2 groups. In the "donor" group, 25 patients (71%) 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). With a median overall follow-up of 31 months, the median LFS in the whole study population was 21 months. In an "intention-to-treat" analysis, the KM estimate of LFS was significantly higher in the "donor" group as compared to the "no donor" group (P=0.01; 54% versus 30% at 4 years). When restricting the analysis to patients who could actually receive the RIC-allo-SCT (median follow-up, 14 months from time of transplantation), 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=0.001; 62% versus 31% at 4 years). In the "transplant" group, RIC-allo-SCT was performed at a median of 209 (range, 119–413) days after diagnosis. No grade 3 or 4 toxicities were encountered during RIC administration, and only 3 patients died from transplant-related toxicity, for an overall cumulative incidence of TRM of 12% (95%CI, 3–32%). This relatively low TRM translated towards a significantly higher overall survival (OS) in the "transplant" group as compared to the "no transplant" group (P=0.01). In the "intention-to-treat" analysis, OS was still significantly higher in the "donor" group as compared to the "no donor" group (P=0.04). Overall, 41 patients (43%; 95%CI, 33–53%) had relapsed at a median of 295 (range, 116–823) days after diagnosis, with the 4-year cumulative incidence of relapse being significantly higher in the "no transplant" group as compared to the "transplant" group (P=0.0002; 54% vs. 12%). After controlling for all relevant factors, in the multivariate analysis, only an intermediate cytogenetic risk group (P=0.01; RR=1.2; 95%CI, 1.2–4.7), and performance of RIC-allo-SCT (P=0.001; RR=4.0; 95%CI, 1.7–9.6), were significantly predictive of an improved LFS, further confirming the overall benefit of RIC-allo-SCT for adult AML patients. Based on these results, and given the low overall TRM rate observed in this high risk population, we conclude that if a matched related donor is identified, RIC-allo-SCT should be proposed since it represents a valid option for AML patients not eligible for standard myeloablative allo-SCT.