Restratifying the prognosis of acute myeloid leukemia patients with CEBPA double mutations based on CSF3R mutations and measurable residual disease

Abstract

Objective: This investigation aims to assess the impact of CSF3R mutations and the presence of measurable residual disease (MRD) on the prognosis of patients with CEBPA double mutations who have acute myeloid leukemia (AML) . Methods: The prognostic significance of these two factors was examined in the present study, which included 66 patients with complete genetic mutations and sequential MRD information. Results: Following the second course of chemotherapy, the MRD status and CSF3R mutations of these patients were linked to their long-term prognosis. CSF3R mutated patients showed inferior relapse-free survival (RFS) (5-year RFS: 15.2% vs 38.7% , P=0.006) and overall survival (OS) (5-year OS: 18.2% vs 60.6% , P=0.038) compared with those with wild-type CSF3R. After the second course of chemotherapy, patients with negative MRD had an RFS of 64 months and an OS of not reaching, which was significantly longer than that of patients with positive MRD (15 and 48 months, and the P value were 0.004 and 0.050, respectively) . CSF3R mutations (HR=0.317, 95% CI 0.129-0.779, P=0.012) , WT1 mutations (HR=0.304, 95% CI 0.115-0.804, P=0.016) , and NRAS mutations (HR=0.153, 95% CI 0.061-0.385, P<0.001) were all independently associated with a poor prognosis for RFS, and CSF3R mutations and positive MRD tended to be independently associated with a poor prognosis for OS, according to the results of a Cox proportional-hazards model analysis (P values were 0.071 and 0.088, respectively) . The patients were divided into three groups based on their CSF3R mutation status and MRD status following treatment: wide-type CSF3R and negative MRD, mutated CSF3R or positive MRD, and mutated CSF3R and positive MRD, which showed significantly different RFS (P<0.001) and OS (P=0.006) . Conclusion: Both CSF3R mutations and positive MRD were associated with poor outcome in AML patients with CEBPA double mutations. An integrity model based on these two factors may be beneficial for accurately evaluating the prognosis of these patients.