PBSC Transplants from Mismatched Unrelated Donors Show Outcomes Similar to Closer Matches

Adults with common blood cancers who received allogeneic transplants from more deeply mismatched unrelated donors achieved outcomes comparable to those seen in patients transplanted with more closely matched donors when post-transplant cyclophosphamide (PTCy) was used, according to findings from the phase 2 ACCESS trial. The research, conducted by NMDP and the Center for International Blood and Marrow Transplant Research (CIBMTR), was presented this month at the American Society of Hematology 2025 Annual Meeting.

Historically, achieving an 8/8 HLA match has been associated with the best transplant outcomes among unrelated donors, while use of more deeply mismatched unrelated donors (MMUD) has been associated with poor survival and higher risk of graft-versus-host disease (GVHD). Prior studies explored the use of PTCy to prevent GVHD prevention in related individuals, but the ACCESS trial is the first to evaluate whether PTCy could reduce this risk in transplants from unrelated donors with as few as 4/8 HLA matches.

The trial enrolled 268 adult patients with common blood cancers who received peripheral blood stem cell (PBSC) grafts from unrelated donors matched at 4/8 to 7/8 HLA alleles. All participants received PTCy. Investigators reported consistent outcomes across all mismatch levels, with one-year overall survival exceeding 80% regardless of donor match. Rates of non-relapse mortality, disease relapse and moderate-to-severe chronic GVHD were also similar between cohorts.

Notably, 62% of the study population were from ethnically diverse backgrounds, patients that have historically faced barriers to finding a fully or closely matched donor. Among these patients, the median number of available donors increased from two at the 7/8 level to 83 at the 6/8 level, and the data suggest that patients searching international registries now have a greater than 99% likelihood of identifying a suitable blood stem cell donor. This supports the idea that use of MMUD could help reduce disparities in transplant access, particularly for patients who are unlikely to identify an 8/8 match.

According to investigators, the findings support the safe use of PTCy–based regimens to expand the pool of unrelated donors and maintain favorable clinical outcomes across a range of HLA match levels.

“We are fundamentally changing what’s possible in transplant medicine and creating a new standard of care for curing common blood cancers,” said Steven M. Devine, MD, chief medical officer, NMDP, and executive lead, CIBMTR. “For the first time, we have clear evidence that patients can safely receive a range of mismatched unrelated donor grafts and achieve survival outcomes on par with those from fully matched donors—this is a giant leap forward for transplant science and medicine.”