Comparative value of post-remission treatment in cytogenetically normal AML subclassified by NPM1 and FLT3 -ITD allelic ratio

Post-remission treatment (PRT) in patients with cytogenetically normal (CN) acute myeloid leukemia (AML) in first complete remission (CR1) is debated. We studied 521 patients with CN-AML in CR1, for whom mutational status of NPM1 and FLT3 -ITD was available, including the FLT3 -ITD allelic ratio. PRT consisted of reduced intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (alloHSCT) ( n =68), myeloablative conditioning (MAC) alloHSCT ( n =137), autologous hematopoietic stem cell transplantation (autoHSCT) ( n =168) or chemotherapy ( n =148). Favorable overall survival (OS) was found for patients with mutated NPM1 without FLT3 -ITD (71±4%). Outcome in patients with a high FLT3 -ITD allelic ratio appeared to be very poor with OS and relapse-free survival (RFS) of 23±8% and 12±6%, respectively. Patients with wild-type NPM1 without FLT3 -ITD or with a low allelic burden of FLT3 -ITD were considered as intermediate-risk group because of similar OS and RFS at 5 years, in which PRT by RIC alloHSCT resulted in better OS and RFS as compared with chemotherapy (hazard ratio (HR) 0.56, P =0.022 and HR 0.50, P =0.004, respectively) or autoHSCT (HR 0.60, P =0.046 and HR 0.60, P =0.043, respectively). The lowest cumulative incidence of relapse (23±4%) was observed following MAC alloHSCT. These results suggest that alloHSCT may be preferred in patients with molecularly intermediate-risk CN-AML, while the choice of conditioning type may be personalized according to risk for non-relapse mortality.