Prospective Evaluation of <i>KIT</i> 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 <i>KIT</i> mutations in pediatric CBF-AML remains controversial. This study aimed to investigate whether incorporating <i>KIT</i> 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. <i>KIT</i> mutations were identified using Sanger sequencing, classified as high-risk in CCLG-AML 2015. Relationships between clinical and biological features, outcomes and <i>KIT</i> mutations were evaluated across genetic subgroups. <i>KIT</i> mutations were identified in 25.4% pediatric CBF-AML, with comparable mutation rates in <i>RUNX1::RUNX1T1</i> and <i>CBFβ::MYH11</i> subgroups. Patients with <i>KIT</i> mutations showed higher leukemia burdens, including increased bone marrow blasts and white blood cell (WBC) indices. <i>RUNX1::RUNX1T1</i> subgroup showed poorer 5-year OS than <i>CBFβ::MYH11</i>. Patients with <i>KIT</i>^mut17+ exhibited significantly lower OS, EFS compared to those with <i>KIT</i>^mut8+ and <i>KIT</i>^wt. Notably, <i>RUNX1::RUNX1T1⁺KIT</i>^mut17<i>⁺</i> patients exhibited significantly worse OS among genetic subgroups but achieved improved OS under CCLG-AML 2015. <i>KIT</i> exon 17 mutational status and treatment protocol was identified as independent prognostic factors for OS and EFS in CBF-AML and <i>RUNX1::RUNX1T1</i>-AML. Our study found that prospective evaluation of <i>KIT</i> mutations is crucial in pediatric CBF-AML, particularly in <i>RUNX1::RUNX1T1</i> patients, where the survival can be significantly improved by high-risk chemotherapy and hematopoietic stem cell transplantation.