Clinicians have traditionally prioritized high-level human leukocyte antigen (HLA) matching to minimize graft-vs-host disease (GVHD) after hematopoietic cell transplantation (HCT). New data from the ACCESS study, sponsored by the National Marrow Donor Program, indicate that the use of cyclophosphamide after HCT can make the procedure safe and effective even when donors and recipients have extensive genetic mismatches. This suggests that clinicians may be able to draw from a much larger donor pool without compromising results. Lead author Antonio Jimenez-Jimenez, MD, of the University of Miami School of Medicine, presented the results of the study at the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 936).
Comparable Survival and GVHD Across Match Levels
In a prospective analysis of 268 adults who were given cyclophosphamide after receiving mismatched unrelated donor transplants, 1-year survival and key transplant outcomes were similar across donor-recipient pairs. The investigators reported that 1-year overall survival—the study’s primary endpoint—was 79% among recipients with seven matched HLA markers and 86% among those with only four to six matches. Rates of relapse (17% and 23%), GVHD-free/relapse-free survival (51% and 55%), and nonrelapse mortality (14% and 8%) were also similar.
Acute grade 2 to 4 GVHD occurred in 39% of patients in the seven-match cohort and 34% of those in the more mismatched group, while moderate-to-severe chronic GVHD at 1 year was 11% and 8%, respectively.
The clinical significance of these results was emphasized by Dr. Jimenez-Jimenez. “With a posttransplant cyclophosphamide-based GVHD prevention strategy, outcomes following mismatched unrelated donor transplant are similar to those achieved with matched donors. This allows us to find donors for virtually everyone, regardless of their ancestry,” he stated.
Implications for Donor Selection and Equity
HLA matching has been particularly challenging for people of non-European descent. For example, Black patients have only a 29% likelihood of finding a fully matched unrelated donor, compared with 89% for non-Hispanic White patients. With a broader range of acceptable HLA matching, physicians may now place greater emphasis on other donor characteristics—such as age—known to influence survival and relapse risk. “This allows us to try to optimize other donor characteristics beyond just HLA matching,” Dr. Jimenez-Jimenez said.
The study also confirms that peripheral blood stem cell grafts—a more commonly used and logistically simpler graft source—can be safely used in this setting. Outcomes were comparable to prior work using bone marrow grafts, broadening options for both donors and transplant centers.
Overall, these findings represent a significant advance in transplant accessibility, suggesting that allogeneic transplantation may now be feasible for many patients who previously lacked a compatible donor. As evidence continues to grow, cyclophosphamide-based GVHD prophylaxis may reshape donor selection practices and improve equity in access to curative therapy.
Disclosure: For full disclosures of all study authors, visit hematology.org.
