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.

Mutation of the TP53 gene in acute lymphoblastic leukemia does not affect survival outcomes after haploidentical hematopoietic stem cell transplantation.

Previous studies have demonstrated that TP53 mutation is correlated with insufficient therapy response and unfavorable prognosis in acute lymphoblastic leukemia (ALL). Few studies have investigated the impact of TP53 mutation in ALL patients after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). We completed a retrospective study of 65 ALL patients with available TP53 status who underwent haplo-HSCT. They were divided into a TP53 mutation group (TP53mut ) and a TP53 wild-type (TP53wt ) group. TP53mut showed comparable 2-year cumulative incidence of relapse (CIR) rates (13.1% vs 12.5%, P = .96) and 2-year leukemia-free survival (LFS) (74.2% vs 77.4%, P = .80) with TP53wt . No significant differences in 2-year overall survival (OS) rates (82.9% vs 87.3%, P = .61) or 2-year NRM rates (12.7% vs 10.2%, P = .69) were observed in TP53mut and TP53wt patients. Multivariate analysis suggested that white blood cell (WBC) count at initial diagnosis (>50 × 109 /L: hazard ratio [HR] = 3.860, P = .016) and age (>40 years old: HR = 4.120, P = .012) are independent risk factors for 2-year LFS. Our study showed that TP53 mutations may not be related to the unfavorable impact on survival in ALL patients after treatment with haplo-HSCT. The present results suggested that haplo-HSCT may eliminate the poor prognosis effect of TP53 mutation in ALL.