Genetic abnormalities predict outcomes in patients with core binding factor acute myeloid leukemia

Research on the comprehensive integration of clinical and genomic characteristics in patients with core binding factor acute myeloid leukemia (CBF-AML) is limited. Clinical and genomic data from consecutive patients with CBF-AML were reviewed. A Cox regression model was used to identify the variables associated with event-free survival (EFS), relapse-free survival (RFS) and overall survival (OS). A total of 346 CBF-AML patients (211 with RUNX1::RUNX1T1 and 135 with CBFB::MYH11) were included in this study. In the RUNX1::RUNX1T1 cohort, multivariate analyses revealed that KDM6A mutations were significantly associated with poor RFS (hazard ratio = 3.1 [1.4, 7.1], p = 0.007) and OS (HR = 11.5 [3.6, 37.0], p < 0.001); FLT3-TKD mutations, poor OS (HR = 4.9 [1.7, 14.3], p = 0.004); KIT mutation VAF > 25%, poor RFS (KITwt as ref, HR = 2.5 [1.1, 5.3], p = 0.022); ASXL1 mutations, favorable EFS (HR = 0.4 [0.2, 0.9], p = 0.016) and OS (HR = 0.2 [0.03, 0.8], p = 0.028). In the CBFB::MYH11 cohort, multivariate analyses revealed that a high mutation burden was significantly associated with inferior OS (HR = 1.4 [1.1, 1.8], p = 0.018); FLT3-ITD mutations, inferior OS (HR = 6.8 [1.3, 36.0], p = 0.024). In addition, increasing age, nonintensive chemotherapy, and high MRD levels predict poor outcomes in the RUNX1::RUNX1T1 cohort. In addition to the adverse impact of high KIT mutation burden and FLT3-ITD or FLT3-TKD mutations on prognosis in CBF-AML, KDM6A mutations predicted poor outcomes in patients with RUNX1::RUXN1T1; however, ASXL1 mutations, favourable outcomes; high mutation burden, poor outcomes in those with CBFB::MYH11.