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

Abstract

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.