TY - JOUR
T1 - Increased Clonal Hematopoiesis in Long-term Survivors of Pediatric Hematopoietic Cell Transplantation
AU - Müskens, Konradin F.
AU - Wieringa, Nienke
AU - van Bergen, Maaike G.J.M.
AU - Bense, Joëll E.
AU - Te Pas, Brigit M.
AU - de Pagter, Anne P.J.
AU - Lankester, Arjan C.
AU - Bierings, Marc B.
AU - Neuberg, Donna S.
AU - Haitjema, Saskia
AU - Kremer, Leontien C.M.
AU - Huls, Gerwin A.
AU - Nierkens, Stefan
AU - Jansen, Joop H.
AU - Lindemans, Caroline A.
AU - de Graaf, Aniek O.
AU - Belderbos, Mirjam E.
N1 - Publisher Copyright:
©2025 The Authors; Published by the American Association for Cancer Research.
PY - 2025/3/4
Y1 - 2025/3/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=86000673951&partnerID=8YFLogxK
U2 - 10.1158/2643-3230.BCD-24-0136
DO - 10.1158/2643-3230.BCD-24-0136
M3 - Article
C2 - 39804695
AN - SCOPUS:86000673951
SN - 2643-3230
VL - 6
SP - 110
EP - 118
JO - Blood cancer discovery
JF - Blood cancer discovery
IS - 2
ER -