Risk Stratification of Cytogenetically Normal Acute Myeloid Leukemia With Biallelic CEBPA Mutations Based on a...

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Approximately 30% of Chinese patients with cytogenetically normal acute myeloid leukemia (CN-AML) harbor biallelic CEBPA (biCEBPA) mutations.
• The prognostic implications and optimal treatment strategies for biCEBPA-mutated CN-AML remain subjects of clinical debate.

Purpose of the Study:

• To develop a risk stratification model for biCEBPA-mutated CN-AML patients.
• To evaluate the efficacy of risk-adapted post-remission therapy, including allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Main Methods:

• Targeted sequencing of 236 genes in 158 biCEBPA-mutated CN-AML patients.
• Construction and validation of a nomogram model based on leukemia-free survival (LFS).
• Kaplan-Meier analysis for risk stratification and comparison of treatment outcomes.

Main Results:

• Mutation number correlated with LFS, overall survival, and cumulative incidence of relapse (CIR).
• A nomogram incorporating white blood cell count, mutations in CFS3R, KMT2A, and DNA methylation genes differentiated low-risk and high-risk subgroups.
• High-risk patients demonstrated significantly poorer LFS compared to low-risk patients in both training and validation cohorts.
• Allo-HSCT markedly improved LFS, survival, and CIR in high-risk patients, but not in low-risk patients.

Conclusions:

• BiCEBPA-mutated CN-AML patients can be stratified into distinct risk groups using four key factors.
• Allogeneic hematopoietic stem cell transplantation is recommended as a post-remission therapy for high-risk patients.
• This risk stratification aids in refining treatment decisions for biCEBPA-mutated CN-AML.