Younger, more mismatched stem cell donors show favorable outcomes in ACCESS trial

Adults with blood cancers who received stem cell transplants from younger, more mismatched unrelated donors had one-year survival rates that matched or beat those of patients who received transplants from closely matched donors, according to results from the ACCESS trial published in Blood Advances.

Transplant physicians have looked for donors whose Human Leukocyte Antigen (HLA) markers, the proteins immune cells use to tell what is a good match and what isn’t, closely match the patient's own. A bigger mismatch was thought to raise the risk of severe graft-versus-host disease (GVHD), a complication in which donor immune cells attack a patient's healthy tissue. Post-transplant cyclophosphamide (PTCy) changed this thought. The drug, first used in transplants between family members, clears out the immune cells most likely to attack the patient's body soon after transplant. This action has let physicians consider donors who once would have been ruled out.

ACCESS is a phase 2 clinical trial sponsored by the National Marrow Donor Program (NMDP) and ran through the Center for International Blood and Marrow Transplant Research (CIBMTR). Researchers enrolled 268 adults at 36 transplant centers. All received blood stem cells from unrelated donors between the ages of 18 and 35, matched at four to seven of eight key HLA markers. Every patient also received tacrolimus and mycophenolate along with PTCy to prevent GVHD. Out of the 268 patients, 183 received grafts matched at seven of eight markers. The other 85 received more mismatched grafts, and most of those, 82.4%, were matched at six of eight markers. Patients were followed for roughly 11.9 months.

A year following transplant, it was found that 78.6% of patients with the closer 7/8 match were still alive, compared with 85.6% of patients with the more mismatched grafts. Relapse occurred in 17.1% of the 7/8 group and 22.8% of the more mismatched group. Death that was not caused by relapse occurred in 13.7% of the 7/8 group and 8.4% of the more mismatched group. Moderate to severe chronic GVHD affected 11.3% of the 7/8 group and 7.7% of the more mismatched group. Severe acute GVHD was uncommon in both groups.

Due to most of the more mismatched grafts coming from six of the eight donors, researchers also compared just the 7/8 and 6/8 groups on their own. The results looked similar.

The study's authors noted that donor match level was not randomly assigned. Physicians chose the best available donor for each patient, so the two groups differed in ways beyond HLA matching.

“The findings should be interpreted as descriptive and hypothesis-generating rather than as demonstrating equivalence” between the two donor groups, the authors wrote in Blood Advances.

Longer follow-up is needed to track relapse, chronic GVHD and survival over time, they added.

Finding a well-matched unrelated donor remains one of the biggest obstacles to transplant, especially for patients of non-European ancestry, who are less likely than white patients to find a fully matched donor, according to past research published by the New England Journal of Medicine.

In ACCESS, patients who received more mismatched grafts were more racially and ethnically diverse than patients with 7/8 matches. Black or African American patients made up 23.5% of the more mismatched group, compared with 8.2% of the closer-matched group.

The study was led by a national team of researchers that included Antonio Martin Jimenez Jimenez, M.D., associate professor of transplantation and cellular therapy at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine. Jimenez Jimenez and his colleagues at Sylvester have helped expand the use of mismatched unrelated donors in day-to-day practice. Mismatched donors are now the most common donor source for stem cell transplants at the center.

“For years, we believed there were hard limits on how much donor mismatch could be safely tolerated. These findings suggest that, with the right transplant platform, we may have more flexibility than previously recognized,” Jimenez Jimenez said in a statement released by the University of Miami Miller School of Medicine.

“The field is moving beyond evaluating a donor based on a single characteristic. Our goal is to identify the best possible donor for each patient, and studies like ACCESS are helping us better understand what that looks like,” Jimenez Jimenez said.