A RECENT study examining long-term effects of allogeneic hematopoietic cell transplantation (HCT) has provided new insights into the behaviour of clonal haematopoiesis (CH) following transplantation. Researchers analysed blood samples from 16 donor-recipient pairs, including the longest surviving HCT recipients in the world, at a median of 33.8 years after the procedure.
The study aimed to determine whether the replicative stress experienced by donor stem cells in the recipient’s body could lead to the disproportionate expansion of CH variants—mutations commonly associated with myeloid malignancies. Using ultrasensitive duplex sequencing, the team investigated mutations in genes recurrently mutated in CH and myeloid cancers, as well as neutral genomic regions.
The results showed that CH variants were present in all donors, including those as young as 12. While the mutation rate was similar between donors and recipients post-HCT (2.0% versus 2.6% per year), the study found that 5.6% of the shared variants showed significantly higher variant allele frequencies (VAF) in the recipients. Notably, the expansion of these variants correlated with the time since the transplant, with older recipients showing more pronounced clonal expansion.
Despite the presence of CH variants, the study concluded that there is no widespread accelerated clonal expansion in transplanted cells even decades after HCT, highlighting the remarkable regenerative capacity of the human hematopoietic system and offering valuable insights for future research into transplant biology and hematologic disease.
Reference
Oshima MU et al. Characterization of clonal dynamics using duplex sequencing in donor-recipient pairs decades after hematopoietic cell transplantation. Science Translational Medicine. 2024;16:770.
