Accelerated Clonal Hematopoiesis in Pediatric and Young Adult Survivors of Childhood Cancer

Clonal hematopoiesis of indeterminate potential(CHIP) is a recognized consequence of aging and a precursor to myelodysplastic syndrome and acute myeloid leukemia which independently increases all-cause mortality in adults. Childhood cancer survivors experience a phenomenon of accelerated aging with increased all-cause mortality; however, the mechanism of this is not known and the prevalence of CHIP not well defined. We prospectively studied 305 pediatric and young adult childhood cancer survivors to determine the prevalence of clonal hematopoiesis(CH). Targeted next-generation sequencing analysis of peripheral blood mononuclear cells elucidated the prevalence of CH (VAF >1%) at a rate of ∼6%, approaching that of adults >50-70 years and much higher than previously reported. This is the first prospective study of CH in pediatric and young adult survivors of childhood cancer and highlights the importance of further investigation to better understand how CH may contribute to treatment-related myeloid neoplasms and other late effects. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by a Hyundai Hope on Wheels Scholar Award granted to Dr. Kathryn E. Dickerson, MD, MSCS ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Full UT Southwestern/Children's Health IRBs gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors