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.
Background on Stem Cell Transplants
Transplant physicians have looked for donors whose Human Leukocyte Antigen (HLA) markers closely match the patient’s own, as 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.
However, post-transplant cyclophosphamide (PTCy) has changed this thought, as the drug clears out the immune cells most likely to attack the patient’s body soon after transplant, allowing physicians to consider donors who once would have been ruled out.
The ACCESS Trial
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), which enrolled 268 adults at 36 transplant centers, all receiving blood stem cells from unrelated donors between the ages of 18 and 35.
These donors were matched at four to seven of eight key HLA markers, and 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, while the other 85 received more mismatched grafts, with most of those (82.4%) matched at six of eight markers.
Results of the Trial
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, while 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, with severe acute GVHD being uncommon in both groups.
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The study’s authors noted that donor match level was not randomly assigned, as physicians chose the best available donor for each patient, so the two groups differed in ways beyond HLA matching.
According to past research, finding a well-matched unrelated donor remains one of the biggest obstacles to transplant, especially for patients of non-European ancestry.
In ACCESS, patients who received more mismatched grafts were more racially and ethnically diverse than patients with 7/8 matches, with Black or African American patients making 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, including Antonio Martin Jimenez Jimenez, M.D., associate professor of transplantation and cellular therapy at the University of Miami Miller School of Medicine.
Jimenez Jimenez and his colleagues have helped expand the use of mismatched unrelated donors in day-to-day practice, with mismatched donors now being 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.
Longer follow-up is needed to track relapse, chronic GVHD, and survival over time, according to the researchers, who also noted that the findings should be interpreted as descriptive and hypothesis-generating rather than as demonstrating equivalence between the two donor groups.
They will continue to monitor the patients to see how the results hold up over time.
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