Abstract 7886: Therapy-related clonal hematopoiesis in pediatric cancer survivors

Abstract Background: Clonal hematopoiesis of indeterminate potential (CHIP) refers to clonal expansion of hematopoietic stem cells due to somatic mutations and is associated with heightened risk of myeloid neoplasms and cardiovascular diseases. Genotoxic therapies such as chemotherapy and radiation therapy are well-recognized contributors to CHIP in adult cancer population. However, CHIP prevalence, mutational patterns, and treatment associations in pediatric populations remain poorly characterized. Methods: We conducted a retrospective analysis of pediatric patients (age ≤ 18) diagnosed with cancer with blood samples collected after cancer therapy. CHIP was defined as the presence of a pathogenic somatic mutation in an accepted driver gene with variant allele frequency (VAF) ≥2%. CHIP prevalence was estimated overall and stratified by histology and therapeutic exposure. Logistic regression with Firth correction and exposure adjustment was used for multivariable analyses. TP53 variants with known Li-Fraumeni syndrome association and VAF 40% were considered germline mutations and excluded from analyses. Results: CHIP mutations were identified in 23 of 1,052 (2.2%) patients in this cohort. Mutations occurred most frequently in the TET2 (26%), DNMT3A (22%), and KRAS (13%) genes. CHIP prevalence was numerically higher among patients who received chemotherapy (3.3% vs. 1.4%, p=0.055). Multivariable analysis showed a modest female predominance (OR 0.45, p=0.04) and a trend toward higher CHIP risk with chemotherapy (OR 1.9, p=0.16). Among drug classes, antimetabolite therapy showed the highest CHIP prevalence (OR 3.46, p = 0.048), driven by methotrexate exposure (OR 21.5, p = 0.001). No correlations were found with age, histology, or radiation. Conclusion: We identified a low overall prevalence of CHIP in pediatric cancer patients and an association with antimetabolite therapy. Further studies are needed to define the long-term clinical implications of clonal hematopoiesis in pediatric cancer survivors.‬‬‬‬ Citation Format: Michael R. Kessler, Yash Pershad, Robert W. Corty, Eric T. Shinohara, Debra Friedman, Alexander G. Bick, Ben H. Park, Leo Y. Luo. Therapy-related clonal hematopoiesis in pediatric cancer survivors abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7886.