After an allogeneic stem cell transplant, recipients face the challenge of rebuilding their blood-forming and immune systems from a small number of donor cells. This process requires the donated cells to replicate extensively, raising concerns about the potential for harmful mutations. Researchers from Fred Hutch Cancer Center conducted a study to explore these concerns, with findings published in Science Translational Medicine.
The study, led by Masumi Ueda Oshima, MD, MA, focused on whether the increased replication of stem cells in recipients leads to more DNA mutations than in donors, especially over long periods. The research involved 16 recipient-donor pairs, with some participants up to 46 years post-transplant. Blood samples were analyzed for genetic mutations, comparing recipients and their donors.
Contrary to expectations, the study found no significant difference in mutation rates between donors and recipients, including in genes linked to blood diseases like myelodysplastic syndrome (MDS) or leukemia. The average mutation rate was 2% per year in donors versus 2.6% per year in recipients. Additionally, mutations passed from donors to recipients did not expand greatly in recipients, with only 5.6% of shared mutations showing a greater-than-10-fold growth advantage in recipients.
These findings have important implications for the use of older donors in stem cell transplants, suggesting that mutations present in older donors do not proliferate significantly in recipients. This offers reassurance about the safety of using older donors when younger ones are not available. The study also has implications for gene therapies, indicating that the replication of transplanted stem cells over many years does not result in the expansion of existing mutations.
Future research directions include studying a larger cohort of transplant recipients to correlate DNA changes with clinical outcomes and exploring the behavior of donor cells over time in the context of current transplantation practices. The study underscores the importance of long-term follow-up in understanding the impacts of stem cell transplantation and gene therapies on recipients' health and longevity.
