FLT3-ITD Allelic Ratio and NPM1 Mutation Do Not Impact Outcomes in Acute Myeloid Leukemia Patients with FLT3-ITD after Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Propensity Score- Matching Study

Abstract

FLT3-ITD mutation has consistently been correlated with poor outcomes in AML patients. Allo-HSCT (allogeneic hematopoietic stem cell transplantation) plays a major role in curing blood diseases. Whether allo-HSCT can eliminate the detrimental effects of FLT3-ITD mutation in AML patients remains debatable. In addition, studies showed that FLT3-ITD allelic ratio (AR) and NPM1 mutation appear to further influence the prognostic utility of FLT3-ITD in patients with FLT3-ITD-mutated AML. The influence of NPM1 mutation and AR on FLT3-ITDmut patients remains unclear in our database. To compare the survival outcomes following allo-HSCT between FLT3-ITDmut and FLT3-ITDwt patients and further analyze the influence of NPM1 and AR on outcomes. 118 FLT3-ITDmut patients and 497 FLT3-ITDwt patients with allo-HSCT were matched 1:3 on the propensity score using a nearest-neighbor matching with a caliper size of 0.2. 430 AML patients were considered, including 116 FLT3-ITDmut patients and 314 FLT3-ITDwt patients. OS (overall survival) and LFS (leukemia-free survival) of FLT3-ITDmut patients were similar to FLT3-ITDwt (2-year OS:78.5% vs 82.6%, P=0.374; 2-year LFS: 75.1% vs 80.8%, P= 0.215). A cut-off of 0.50 was applied to define subgroups with a low or high AR of FLT3-ITD, no significant CIR (cumulative incidence of relapse) and LFS differences were observed between the low AR and high AR groups (2-year CIR: P=0.617; 2-year LFS: P=0.563). CIR and LFS were comparable when patients were grouped according to the presence or absence of NPM1 and FLT3-ITD (2-year CIR: P=0.356; 2-year LFS: P=0.159). Additionally, the CIR and LFS of FLT3-ITDmut and FLT3-ITDwt patients tended to be different after MSD-HSCT (matched-sibling donor hematopoietic stem cell transplantation) (2-year CIR: P= 0.072; 2-year LFS: P= 0.084), however, the differences were not observed in patients with haplo-HSCT (2-year CIR: P= 0.59; 2-year LFS: P= 0.794). The presence of MRD before transplantation and non-CR1 were risk factors related to inferior outcomes in a multivariate analysis, regardless of FLT3-ITD or NPM1 status. Our results suggested that allo-HSCT, especially haplo-HSCT, may overcome the adverse effect of FLT3-ITD mutation, regardless of the NPM1 status or AR. Allo-HSCT could be an ideal option for AML patients with FLT3-ITD.