Younger mismatched donors expand stem-cell transplant options

At Sylvester Comprehensive Cancer Center in Miami, the search for a stem-cell donor is no longer governed by a close-match rule alone. An analysis of the ACCESS trial found 85.6% overall survival one year after transplantation among patients who received cells from younger, more genetically mismatched unrelated donors—an approach that could widen options for people with blood cancers when a closer donor cannot be found.

The study, led by a national team including Antonio Martin Jimenez Jimenez of the University of Miami Miller School of Medicine, examined 268 adults receiving peripheral blood stem cells. Most of the more mismatched grafts came from donors matched at six of eight key HLA markers, the immune-system markers traditionally used to judge donor compatibility. A comparison group received grafts from donors matched at 7/8 markers; its one-year overall survival was 78.6%.

The treatment platform helped make that broader search possible. All patients received PTCy after transplantation. The treatment selectively removes highly reactive donor immune cells, which can attack the recipient's healthy tissues, helping donor cells take hold while reducing the risk of graft-versus-host disease, or GVHD—a serious complication in which transplanted immune cells attack the patient. Severe acute and chronic GVHD rates remained relatively low in both groups, while relapse and non-relapse mortality rates were also favorable.

The donor pool was not the only variable under review. Every donor in the ACCESS analysis was between 18 and 35 years old, allowing researchers to examine a uniformly young group; the study authors note that younger age can influence transplant outcomes. Their conclusion is narrower than a declaration of equivalence: the analysis was exploratory, donor assignments were not randomized, and longer follow-up is needed for survival, relapse and chronic GVHD.

Concretely, patients who cannot secure a fully matched unrelated donor may have another carefully assessed route to transplantation, rather than waiting for a perfect match that may be unavailable or impractical. Sylvester's clinicians have already expanded their use of mismatched unrelated grafts, which now represent the center's primary donor source for allogeneic hematopoietic cell transplantation. The research points toward choosing a donor through several characteristics—not HLA match status alone—while leaving the long-term comparison still to be established.