Prospective Evaluation of KIT Mutations and Long-Term Outcomes in Pediatric Core Binding Factor Acute Myeloid Leukemia: A Single Institutional Study in China

The overall incidence of core binding factor acute myeloid leukemia (CBF-AML) in pediatric patients has been reported to be 19%–44.3%. However, the prognostic role of KIT mutations in pediatric CBF-AML remains controversial. This study aimed to investigate whether incorporating KIT mutation status into risk stratification improves long-term outcomes. A total of 114 pediatric CBF-AML patients treated under BCH-AML 2005 protocol and CCLG-AML 2015 protocol were enrolled. KIT mutations were identified using Sanger sequencing, classified as high-risk in CCLG-AML 2015. Relationships between clinical and biological features, outcomes and KIT mutations were evaluated across genetic subgroups. KIT mutations were identified in 25.4% pediatric CBF-AML, with comparable mutation rates in RUNX1::RUNX1T1 and CBFβ::MYH11 subgroups. Patients with KIT mutations showed higher leukemia burdens, including increased bone marrow blasts and white blood cell (WBC) indices. RUNX1::RUNX1T1 subgroup showed poorer 5-year OS than CBFβ::MYH11. Patients with KITmut17+ exhibited significantly lower OS, EFS compared to those with KITmut8+ and KITwt. Notably, RUNX1::RUNX1T1+KITmut17+ patients exhibited significantly worse OS among genetic subgroups but achieved improved OS under CCLG-AML 2015. KIT exon 17 mutational status and treatment protocol was identified as independent prognostic factors for OS and EFS in CBF-AML and RUNX1::RUNX1T1-AML. Our study found that prospective evaluation of KIT mutations is crucial in pediatric CBF-AML, particularly in RUNX1::RUNX1T1 patients, where the survival can be significantly improved by high-risk chemotherapy and hematopoietic stem cell transplantation.