Characteristics of Donor and Recipient Clonal Hematopoiesis in Nonmyeloablative Transplant for Sickle Cell Disease.

We used error-corrected DNA sequencing to detect clonal hematopoiesis variants at a variant allele fraction > 0.0005 in blood samples from 98 individuals with sickle cell disease and 72 non-sickle cell disease donor controls who underwent HCT at the NIH between July 2004 and June 2023.

Following HCT, the proportion of sickle cell disease recipients with clonal hematopoiesis increased, driven primarily by mutations in DNMT3A/TET2 and TP53.

All cases of donor-derived clonal hematopoiesis involved DNMT3A/TET2 mutations, while persistent-recipient clonal hematopoiesis involved DNA Damage Response mutations.