Study Finds Stem Cell Transplants Safe With Mismatched, Unrelated Donors

A new multicenter study suggests that patients with blood cancers can safely receive stem cell transplants from unrelated donors even when there is significant genetic mismatch, a finding that could dramatically expand access to life-saving treatment—particularly for patients from underrepresented ethnic backgrounds.

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The research was led by a national team that includes Dr. Antonio Jimenez Jimenez, associate professor of medicine in the Division of Transplantation and Cellular Therapy at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine. The findings are being presented on December 8 at the American Society of Hematology (ASH) Annual Meeting in Orlando and were highlighted during an ASH press briefing earlier in the week.

For decades, successful stem cell transplantation relied on finding donors who matched patients at eight key human leukocyte antigen (HLA) markers. While effective, this standard excluded many patients—especially those of non-European ancestry—from finding suitable donors. According to national registry data, only about 29 percent of Black patients can locate a fully matched donor, compared with nearly 90 percent of non-Hispanic white patients.

The new findings come from the ACCESS trial, sponsored by the National Marrow Donor Program, which examined outcomes using a graft-versus-host disease (GVHD) prevention strategy based on post-transplant cyclophosphamide (PTCy). This approach allows clinicians to use donors who are mismatched at two or more HLA markers without significantly increasing complications.

The trial enrolled 268 adults with blood cancers who received peripheral blood stem cell transplants from unrelated donors aged 35 or younger. Of these patients, 183 received grafts matched at seven of eight HLA markers, while 85 received grafts matched at only four to six markers. After one year, survival rates were comparable between the two groups—86 percent in the more mismatched group and 79 percent in the less mismatched group.

Rates of acute and chronic GVHD were also similar. At six months, acute grade II–IV GVHD occurred in 34 percent of patients with four to six matches and 39 percent of those with seven matches. At one year, moderate-to-severe chronic GVHD affected 8 percent and 11 percent of patients, respectively. Notably, 61 percent of patients in the more mismatched donor group identified as other than non-Hispanic white.

The results suggest that donor availability may no longer be the primary barrier it once was. With PTCy-based immune suppression, physicians can prioritize other donor characteristics—such as younger age—that are known to improve transplant outcomes, rather than focusing almost exclusively on genetic matching.

Cyclophosphamide works by targeting immune cells most likely to trigger GVHD after transplantation, allowing the donor cells to engraft while reducing harmful immune reactions. Investigators say this strategy has reshaped donor utilization in recent years, and the ACCESS trial provides some of the strongest evidence to date that it can be applied safely even in highly mismatched, unrelated donor settings.

While researchers caution that the study was not randomized and that further research is needed—particularly in pediatric populations—the data indicate that up to 99 percent of patients could now have access to a viable donor through international registries.

Antonio Jimenez Jimenez, M.D., associate professor of medicine in the division of transplantation and cellular therapy at Sylvester Comprehensive Cancer Center

More information about ongoing research can be found through Sylvester Comprehensive Cancer Center, with updates shared on X via @SylvesterCancer.

By ML Staff.