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

FLT3-ITD mutation has consistently been correlated with poor outcomes in patients with acute myeloid leukemia (AML). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) 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 have shown that the 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 in our database remains unclear. We aimed to compare survival outcomes following allo-HSCT between patients with FLT3-ITDmut and those with wild-type FLT3-ITD and to further analyze the influence of NPM1 and AR on outcomes. A total of 118 FLT3-ITDmut patients and 497 FLT3-ITDwt patients who underwent allo-HSCT were propensity score-matched 1:3 using nearest-neighbor matching with a caliper size of .2. The study cohort comprised 430 patients with AML, including 116 with FLT3-ITDmut and 314 with FLT3-ITDwt. Overall survival (OS) and leukemia-free survival (LFS) were similar in the FLT3-ITDmut patients and the FLT3-ITDwt patients (2-year OS,78.5% versus 82.6% [P = .374]; 2-year LFS, 75.1% versus 80.8% [P = .215]). A cutoff of .50 was applied to define subgroups with low and high FLT3-ITD AR. No significant differences in the cumulative incidence of relapse (CIR) or LFS were observed between the low AR and high AR groups (2-year CIR, P = .617; 2-year LFS, P = .563). CIR and LFS also were comparable when patients were grouped according to the presence or absence of NPM1 and FLT3-ITD (2-year CIR, P = .356; 2-year LFS, P = .159). Additionally, the CIR and LFS of FLT3-ITDmut and FLT3-ITDwt patients tended to differ after matched sibling donor HSCT (2-year CIR, P = .072; 2-year LFS, P = .084); however, these differences were not seen in recipients of haploidentical (haplo-) HSCT (2-year CIR, P = .59; 2-year LFS, P = .794). The presence of minimal residual disease before transplantation and lack of first complete response were identified as risk factors related to inferior outcomes in a multivariate analysis regardless of FLT3-ITD or NPM1 status. Our results suggest that allo-HSCT, especially haplo-HSCT, may overcome the adverse effect of FLT3-ITD mutation irrespective of NPM1 status or AR. Allo-HSCT could be an ideal option for AML patients with FLT3-ITD.