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Updated: Sep 10, 2025
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Prognostic covariates associated with outcomes in patients with NPM1-mutated acute myeloid leukemia
Shunjie Yu1, Sen Yang1, Lijuan Hu1
1Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University, Beijing 100044, China.
Background:
NPM1 mutacute myeloid leukemia (AML) patients have greater heterogeneity. However, data on the comprehensive integration of clinical and genetic data in NPM1mutAML patients are limited, especially in the FLT3 inhibitor era.
Methods:
Data from consecutive AML patients with NPM1mut/FLT3-ITDwt (n = 203) and NPM1mut/FLT3-ITDmut (n = 115) were reviewed.
Results:
In NPM1mut/FLT3-ITDwt patients, in multivariate analyses male sex, WBC count ≥19 × 109/L, bone marrow blasts ≥ 70%, NPM1 non-A/B/D type mutation, TET2 mutation and measurable residual disease (MRD) positivity after the first cycle of consolidation were significantly-associated with poor relapse-free survival (RFS) and survival. Based on the adverse prognostic covariates, patients were classified into low-risk (score 0-2, n = 113, 64%), intermediate-risk (score 3, n = 43, 25%) and high-risk (score ≥4, n = 20, 11%) subgroups, with significant differences in 3-year probabilities of RFS and survival (all P values < .001). In NPM1mut/FLT3-ITDmut patients who did not undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) in CR1, single FLT3-ITD mutation, NPM1 non-A/B/D type mutation, TET2 mutation and MRD positivity after the first cycle of consolidation, poor RFS; platelet ≤60 × 109/L and albumin <40 g/L, poor survival. Patients were classified into low-risk (score 0-2) allo-HSCT (n = 9, 11%) or non-allo-HSCT (n = 26, 31%), and high-risk (score ≥ 3) allo-HSCT (n = 8, 10%) or non-allo-HSCT (n = 40, 48%). The first 3 subgroups had comparable outcomes, but were significantly superior to the high-risk non-allo-HSCT subgroup (all P values for trend = .001-.010).
Conclusions:
We identified high-risk AML patients with NPM1mut/FLT3-ITDwt or NPM1mut/FLT3-ITDmut who might consider more intensive therapy.
Insights
This study identifies risk factors for poor outcomes in acute myeloid leukemia (AML) with NPM1 mutations. High-risk patients may benefit from more intensive therapies, guiding personalized treatment strategies.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Acute myeloid leukemia (AML) with NPM1 mutations exhibits significant heterogeneity.
- Limited data exists on integrating clinical and genetic factors in NPM1-mutated AML, particularly with FLT3 inhibitors.
Purpose of the Study:
- To comprehensively integrate clinical and genetic data in NPM1-mutated AML patients.
- To identify prognostic factors and stratify patients based on risk.
- To guide treatment decisions in the era of FLT3 inhibitors.
Main Methods:
- Retrospective review of consecutive AML patients with NPM1 mutations and FLT3-ITD wild-type (n=203) or FLT3-ITD mutated (n=115) status.
- Multivariate analyses to identify factors associated with relapse-free survival (RFS) and overall survival.
- Risk stratification based on identified prognostic covariates.
Main Results:
- In NPM1-mutated/FLT3-ITD-wild-type AML, male sex, high WBC count, high bone marrow blasts, non-A/B/D NPM1 mutations, TET2 mutations, and MRD positivity were linked to poor RFS and survival.
- Patients were stratified into low, intermediate, and high-risk subgroups with significant survival differences (p < 0.001).
- In NPM1-mutated/FLT3-ITD-mutated AML, FLT3-ITD mutation, non-A/B/D NPM1 mutations, TET2 mutations, and MRD positivity predicted poor RFS; low platelets and albumin indicated poor survival. Risk stratification also showed significant outcome differences.
Conclusions:
- Identified high-risk subgroups within NPM1-mutated AML (both FLT3-ITD wild-type and mutated).
- These findings suggest that patients in high-risk groups may benefit from more intensive therapeutic approaches.
- This study provides a basis for personalized treatment strategies in NPM1-mutated AML.
