A recent study from Japan involving more than 7,400 patients has found that a specific genetic mismatch significantly raises the risk of severe acute graft-versus-host disease (GVHD) after umbilical cord blood transplantation. The research, conducted by scientists at Fujita Health University and published in Transplantation and Cellular Therapy, shows that a particular human leukocyte antigen (HLA) mismatch between donor and recipient triples the likelihood of life-threatening immune complications.
Umbilical cord blood transplantation is often used for treating blood cancers and other serious hematological disorders when matched donors are not available. Although cord blood can usually tolerate genetic mismatches better than other sources, severe immune reactions remain a concern. The study led by Associate Professor Takakazu Kawase from the Department of Immune Regenerative Medicine at Fujita Health University analyzed data from 7,462 Japanese patients aged 16 and older who underwent their first unrelated cord blood transplant.
The researchers focused on how different HLA mismatch combinations influence patient outcomes. They found that when the donor had HLA-C*03:04 and the recipient had HLA-C*14:02, there was a threefold increase in the risk of developing severe (grade III–IV) acute GVHD. This result remained significant even after accounting for multiple variables such as age, disease status, conditioning regimen, cell dose, and overall number of mismatches.
Dr. Kawase stated, "This study shows that even in cord blood transplantation, where HLA mismatches are generally better tolerated, specific HLA combinations can provoke very strong immune reactions." He added, "Identifying these high-risk mismatches gives us an opportunity to improve donor selection and reduce life-threatening complications."
The study also examined how severe GVHD affects survival rates. While moderate forms of GVHD might be linked to better outcomes due to beneficial immune effects, severe grade III–IV cases were associated with about an 80% higher risk of death.
By using this new information in donor selection processes for cord blood transplants, clinicians may be able to avoid high-risk combinations when possible. Dr. Kawase explained further: "We have been engaged in long-term analysis of transplant registry data with the goal of building solid evidence that improves patient outcomes. In earlier work, we were the first to identify high-risk HLA mismatch combinations in unrelated bone marrow transplantation, and this study is a continuation of that effort in cord blood transplantation."
The research team believes ongoing studies into genetic factors behind severe GVHD will help refine stem cell transplant strategies over the next decade.
