Engrafted donor-derived clonal hematopoiesis after allogenic hematopoietic cell transplantation is associated with chronic GVHD requiring immunosuppressive therapy, but no adverse impact on OS or relapse.

Clonal hematopoiesis of indeterminate potential (CHIP) is an age-associated condition defined by the presence of a somatic mutation in a leukemia-associated gene in individuals who otherwise have no evidence of a hematologic malignancy. In the allogeneic hematopoietic cell transplant (HCT) setting, clonal hematopoiesis (CH) mutations present in donor stem cells can be transferred to recipients at the time of HCT. As the consequences of donor-derived CH in HCT recipients are not entirely clear, we sought to investigate clinical outcomes in patients with engrafted donor-derived CH using a matched cohort analysis of both related and unrelated donors. Of 209 patients with next-generation sequencing performed before and after HCT, donor-derived CH mutations were detected in 15 transplant recipients (5.2%). DNMT3A was the most commonly mutated gene (9/15, 60%). Mutations in SF3B1, CSF3R, STAT3, CBLB, TET2, and ASXL1 were also identified. Donor-derived CH was not associated with delayed neutrophil or platelet engraftment, and there was no impact on conversion to full donor chimerism. No patients with donor-derived CH experienced relapse, in contrast to 15.6% (7/45) in the matched control cohort without CH (p=0.176). Donor-derived CH was not associated with worse overall survival; however, patients with donor-derived CH were more likely to develop chronic GVHD requiring systemic immunosuppressive therapy (IST) (p=0.045), and were less likely to discontinue IST (p=0.03), compared to controls without donor-derived CH. We conclude that donor-derived CH does not have an adverse impact on relapse, survival, or engraftment outcomes, but may potentiate a graft versus leukemia effect reflected by increased chronic GVHD requiring IST.