IKZF1 Variants Predicted Poor Outcomes in Acute Myeloid Leukemia Patients with CEBPA bZIP In-Frame Mutations

IKZF1变异预示着伴有CEBPA bZIP框内突变的急性髓系白血病患者预后不良

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Abstract

Background: CCAAT/enhancer-binding protein alpha-basic leucine zipper in-frame (CEBPA(bZIP-inf)) mutations are associated with favorable outcomes in acute myeloid leukemia (AML). So far, there are limited data on integrating clinical and genomic features impacting the outcomes. Methods: Clinical and genomic data from consecutive patients with CEBPA(bZIP-inf) were reviewed. A Cox proportional hazards regression was used to identify the variables associated with event-free survival (EFS), relapse-free survival (RFS) and survival. Results: 224 CEBPA(bZIP-inf) patients were included in this study. In the 201 patients, except for the 19 receiving the transplant in the first complete remission with no events (the transplant cohort), multivariate analyses showed that IKZF1 mutations/deletions were significantly associated with poor EFS (p = 0.001) and RFS (p < 0.001); FLT3-ITD mutations, poor RFS (p = 0.048). In addition, increasing WBC count, lower hemoglobin concentration, non-intensive induction, and MRD positivity after first consolidation predicted poor outcomes. On the basis of the number of adverse prognostic covariates for RFS, the 201 patients were classified into low-, intermediate- or high-risk subgroups, and there were significant differences in the 3-year EFS, RFS and survival rates (all p < 0.001); however, except for survival in the low-risk group, these metrics were lower than those in the transplant cohort. Conclusions: We identified a potential high-risk population with adverse prognostic factors in CEBPA(bZIP-inf) AML patients for which transplantation should be considered.

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