Impact of FLT3 internal tandem duplication and NPM1 mutations in acute myeloid leukemia treated with allogeneic hematopoietic cell transplantation

Background aims: The internal tandem duplication of FLT3 (FLT3(ITD)) and NPM1 mutations (NPM1(mut)) are well-established prognostic factors in cytogenetically intermediate-risk acute myeloid leukemia (AML) when treated with chemotherapy alone. However, their prognostic value in the setting of allogeneic hematopoietic cell transplantation (HCT) is controversial. Methods: FLT3 and NPM1 mutational status was determined at diagnosis using single-gene polymerase chain reaction or next-generation sequencing in 247 adult patients with cytogenetically intermediate-risk AML who underwent myeloablative HCT. Multivariate Fine-Gray and Cox regression was used to analyze the cumulative incidence of relapse (CIR), relapse-free survival (RFS) and overall survival (OS). Results: FLT3(ITD) and NPM1(mut) were present in 74 of 247 (30%) and 79 of 247 (32%) patients, respectively. There was no significant difference between patients without a FLT3(ITD) or NPM1(mut) (FLT3(NONITD)/NPM1(WT)) and patients with a FLT3(ITD) mutation alone (FLT3(ITD)/NPM1(WT)) with regard to CIR (P = 0.60), RFS (P = 0.91) or OS (P = 0.66). Similarly, there was no significant difference between FLT3(NONITD)/NPM1(WT) and FLT3(NONITD)/NPM1(mut) patients with regard to CIR (P = 0.70), RFS (P = 0.75) or OS (P = 0.95). The presence of a concurrent mutation in NPM1 did not appear to modify the impact of having a FLT3(ITD) mutation. Conclusions: In contrast to chemotherapy-only treatment, FLT3 and NPM1 mutational status does not appear to predict outcomes in patients with cytogenetically intermediate-risk AML following HCT. These results suggest that HCT may ameliorate the poor prognostic effect of FLT3(ITD) mutation and that HCT should be considered over chemotherapy-only treatment in FLT3(ITD)-mutated AML. (C) 2021 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.