Clinical Outcomes of Acute Myeloid Leukemia Patients Harboring the RUNX1 Mutation: Is It Still an Unfavorable Prognosis? A Cohort Study and Meta-Analysis

SIMPLE SUMMARY: Acute myeloid leukemia (AML) with mutated RUNX1 (RUNX1(mut)) has an adverse prognosis based on the 2022 European LeukemiaNet risk stratification. However, the WHO classifications of 2022 removed RUNX1 mutations from the unique entity because of various prognoses and treatment outcomes. Intriguingly, the overall survival (OS) and relapse-free survival (RFS) outcomes were similar in patients who had de novo AML with intermediate-risk cytogenetics with and without RUNX1(mut). Our study endorsed an unfavorable prognosis of this entity. ABSTRACT: Acute myeloid leukemia (AML) with mutated RUNX1 (RUNX1(mut)) is considered to have an unfavorable prognosis. However, recent studies have reported comparable survival outcomes with wild-type RUNX1 (RUNX1(wt)). To assess the clinical outcomes of AML with and without RUNX1(mut), we performed a prospective cohort study and systematic review and meta-analysis. The study enrolled 135 patients (27 with RUNX1(mut); 108 with RUNX1(w)(t)). There were no significant differences in the median OS and RFS of the RUNX1(mut) and RUNX1(wt) groups (9.1 vs. 12.2 months; p = 0.268 and 7.8 vs. 14.6 months; p = 0.481, respectively). A subgroup analysis of de novo AML patients with intermediate-risk cytogenetics showed similar outcomes. Our meta-analysis pooled data from 23 studies and our study. The complete remission rate was significantly lower in the RUNX1(mut) group (pooled odds ratio: 0.42). The OS, RFS, and event-free survival rates also favored the RUNX1(wt) group (pooled risk ratios: 1.36, 1.37, and 1.37, respectively). A subgroup analysis of de novo AML patients with intermediate-risk cytogenetics demonstrated nearly identical OS and RFS outcomes. This study confirms that patients with AML and RUNX1(mut) had poor prognoses. Nonetheless, in de novo AML with intermediate-risk cytogenetics, the survival outcomes of both groups were comparable.