Increased Prevalence of Clonal Hematopoiesis in Children with Sickle Cell Disease

Recent studies have reached opposing conclusions about whether clonal hematopoiesis (CH) is increased or decreased in patients with sickle cell disease (SCD). Given that CH is typically age-related, its presence in children with SCD could offer unique insights into early-life mutagenesis and disease-related stressors. We tested the primary and secondary hypotheses, that children with SCD would have a higher prevalence of CH when compared to age, sex, and race matched children without SCD; and children with hydroxyurea would have a higher CH prevalence than children not treated with hydroxyurea. To address this, we conducted a cross-sectional study in two independent cohorts of children, ages 0-18 years, with SCD (n=1,025 and n=1,293, respectively) and a 2,957-person matched comparison group. Using a highly sensitive, error-corrected sequencing assay capable of detecting CH at a variant allele frequency ≥ 0.5%, we found that children with SCD have a significantly higher prevalence of CH in relation to the comparison group (odds ratio (OR)=4.2, p=7.4x10-13). Additionally, CH was not associated with exposure to hydroxyurea therapy (OR=0.76, p=0.44).