Clonal Dynamics After Allogeneic Hematopoietic Stem Cell Transplantation from Related Donors: A Case Series
TL;DR
The study showed that the re-emergence of recipient-derived clones, particularly oncogenic DNMT3A mutations, frequently preceded graft failure or disease relapse, and suggested that comprehensive molecular screening of donors and longitudinal molecular monitoring of recipients may be essential to optimize transplant outcomes and personalize post-HSCT management.
Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) serves as a critical model for investigating clonal dynamics, as hematopoietic reconstitution occurs amidst significant proliferative stress and immune-mediated pressures. This study utilized longitudinal next-generation sequencing of a 30-gene panel to track clonal evolution in 20 patients and their matched-related or haploidentical donors. The findings revealed that post-transplant hematopoiesis is frequently driven by donor-derived clones, with DNMT3A being the most prevalent mutation in the study population. A key finding was the significant association between the presence of the donor TET2 Leu1721Trp variant and reduced overall survival in recipients (median 14.3 months compared with 50.8 months for wild type; p = 0.0100). Additionally, the study showed that the re-emergence of recipient-derived clones, particularly oncogenic DNMT3A mutations, frequently preceded graft failure or disease relapse. These findings suggest that, although donor clonal hematopoiesis is generally considered clinically neutral, specific genetic variants can profoundly influence clinical outcomes, suggesting that comprehensive molecular screening of donors and longitudinal molecular monitoring of recipients may be essential to optimize transplant outcomes and personalize post-HSCT management.