BACKGROUND: Core-binding factor acute myeloid leukemia (CBF-AML) is characterized by t(8
21) or inv(16)/t(16
16) chromosomal rearrangements. METHODS: In this retrospective study of 71 CBF-AML cases from Qatar's National Center for Cancer Care &
Research (2013-2022), we analyzed clinicopathological characteristics and survival outcomes. RESULTS: The cohort was predominantly male (76%) with a median age of 40 years, and 96% were de novo AML. The t(8
21) translocation was more frequent (69%) than inv(16)/t(16
16). Patients under 40 years showed higher white blood cell counts and blast percentages. Standard "3+7" induction chemotherapy (used in 69% of cases) achieved remission in 67% of patients. Median overall survival was 81% at 37 months, with median progression-free survival of 34 months. No significant survival differences were observed based on FLT3-ITD status, translocation type, complex karyotype, KIT mutation status, or allogeneic stem cell transplantation (performed in 19% of patients), though patients under 60 years demonstrated better survival outcomes. CONCLUSIONS: This study highlights CBF-AML heterogeneity and challenges established prognostic markers, suggesting a need for risk stratification reassessment, treatment strategy optimization, ELN guidelines implementation, and continuous molecular monitoring.