Increased Clonal Hematopoiesis in Long-term Survivors of Pediatric Hematopoietic Cell Transplantation

Abstract

In pediatric hematopoietic cell transplantation (HCT) recipients, transplanted donor cells may need to function far beyond normal human lifespan. In this study, we investigated the risk of clonal hematopoiesis (CH) in 144 pediatric long-term HCT survivors and 258 nontransplanted controls. CH was detected in 16% of HCT recipients and 8% of controls at variant allele frequencies of 0.01 to 0.31. Mutations were predominantly in DNMT3A (80%) and TET2 (20%). Older hematopoietic age (OR: 1.07; P < 0.001) and the HCT procedure (OR: 2.53; P = 0.02) independently increased the risk of CH, indicating both aging- and transplantation-induced effects. Large clones (variant allele frequency >0.10) were found exclusively in HCT recipients. Notably, CH was also detected within 15 years after a cord blood HCT. Inflammatory processes around graft infusion were associated with CH presence. Future studies are required to track the evolution of posttransplant CH and its impact on future cardiovascular diseases, second malignancies, and overall survival. SIgnIfICAnCe: As survival of HCT recipients continues to improve, late treatment effects gain importance. We demonstrate that pediatric HCT recipients show increased risk of CH compared with age-matched controls. Prospective studies are crucial to understand the clinical implications of posttransplant CH in this young population.