Increased clonal hematopoiesis in long-term survivors of pediatric hematopoietic cell transplantation
Müskens KF, Wieringa N, van Bergen MGJM, Bense JE, Te Pas BM, de Pagter APJ, Lankester AC, Bierings MB, Neuberg DS, Haitjema S, Kremer LCM, Huls GA, Nierkens S, Jansen JH, Lindemans CA, de Graaf AO, Belderbos ME
In pediatric hematopoietic cell transplantation (HCT) recipients, transplanted donor cells may need to function far beyond normal human lifespan. Here, we investigated the risk of clonal hematopoiesis (CH) in 144 pediatric long-term HCT survivors and 258 non-transplanted controls. CH was detected in 16% of HCT recipients and 8% of controls, at variant allele frequencies (VAFs) of 0.01-0.31. Mutations were predominantly in DNMT3A (80%) and TET2 (20%). Older hematopoietic age (odds ratio: 1.07, p<0.001) and the HCT procedure (odds ratio: 2.53, p=0.02) independently increased the risk of CH, indicating both aging- and transplantation-induced effects. Large clones (VAF >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 post-transplant CH and its impact on future cardiovascular disease, second malignancies and overall survival.
Blood cancer discovery, 2025-01-15