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Published on: September 20, 2016
FLT3-ITD Allelic Ratio and NPM1 Mutation Do Not Impact Outcomes in Acute Myeloid Leukemia Patients with FLT3-ITD
Cuiyan Zhou1, Fengmei Zheng1, Lanping Xu1
1Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; National Clinical Research Center for Hematologic Disease, Beijing, China; Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing 100044, China.
Abstract:
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.
Insights
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may overcome negative outcomes associated with the FLT3-ITD mutation in acute myeloid leukemia (AML). This approach, particularly haplo-HSCT, offers a promising treatment option for AML patients with this mutation.
Area of Science:
- Hematology
- Oncology
- Transplantation Immunology
Background:
- The FLT3-ITD mutation is a known poor prognostic marker in acute myeloid leukemia (AML).
- Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for AML, but its efficacy in overcoming FLT3-ITD mutations is debated.
- The influence of FLT3-ITD allelic ratio (AR) and NPM1 mutation status on outcomes after allo-HSCT in AML patients requires further clarification.
Purpose of the Study:
- To compare survival outcomes between FLT3-ITD mutated (FLT3-ITDmut) and wild-type (FLT3-ITDwt) AML patients undergoing allo-HSCT.
- To investigate the impact of NPM1 mutation and FLT3-ITD AR on the prognostic value of FLT3-ITD in AML patients receiving allo-HSCT.
Main Methods:
- Propensity score matching was used to create comparable cohorts of FLT3-ITDmut (n=116) and FLT3-ITDwt (n=314) AML patients who underwent allo-HSCT.
- Overall survival (OS), leukemia-free survival (LFS), and cumulative incidence of relapse (CIR) were analyzed.
- Subgroup analyses were performed based on FLT3-ITD AR (high vs. low) and NPM1 mutation status.
Main Results:
- No significant differences in 2-year OS or LFS were observed between FLT3-ITDmut and FLT3-ITDwt AML patients post-allo-HSCT.
- FLT3-ITD AR and NPM1 mutation status did not significantly impact CIR or LFS.
- While a trend towards differing outcomes was noted after matched sibling donor HSCT, haploidentical (haplo-) HSCT showed comparable results irrespective of FLT3-ITD status.
- Minimal residual disease before transplantation and lack of first complete response were independent risk factors for inferior outcomes.
Conclusions:
- Allo-HSCT, especially haplo-HSCT, appears to mitigate the adverse prognostic impact of the FLT3-ITD mutation in AML, irrespective of NPM1 status or AR.
- Allo-HSCT represents a viable and potentially curative option for AML patients with FLT3-ITD mutations.
