“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,” said Antonio Martin Jimenez Jimenez, M.D., associate professor of clinical medicine in the Division of Transplantation and Cellular Therapy at Sylvester Comprehensive Cancer Center.

Findings challenge long-held assumptions about how closely transplant donors must genetically match patients.

Article Summary

• New findings from the ACCESS clinical trial suggest that carefully selected stem cell donors with greater genetic mismatches may still provide encouraging outcomes for patients with blood cancers.
• The research builds on years of work showing that post-transplant cyclophosphamide can safely broaden donor options while maintaining strong transplant outcomes.
• The findings add to growing evidence that donor selection is becoming more sophisticated, incorporating factors such as donor age alongside traditional genetic matching.

MIAMI  – Aug. 20, 2026 – Blood cancer patients who cannot find a closely matched stem cell donor may have more transplant options than previously thought. New findings from the ACCESS trial suggest carefully selected younger donors with greater genetic mismatches can produce encouraging outcomes, potentially widening access to a potentially lifesaving transplant.

For decades, stem cell transplantation has operated under a simple rule: the closer the donor match, the better. Patients with leukemia, lymphoma, myelodysplastic syndromes and other blood cancers often faced an extensive search for a donor whose immune system markers aligned as closely as possible with their own.

Now, a study in Blood Advances, led by a national team of investigators that includes Antonio Martin Jimenez Jimenez, M.D., associate professor of clinical medicine in the Division of Transplantation and Cellular Therapy at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, suggests that rule may be evolving. Researchers found encouraging outcomes among patients who received stem cell transplants from younger, more genetically mismatched unrelated donors than have traditionally been used.

Historically, physicians avoided donors with significant genetic differences because those mismatches increased the risk that donor immune cells would attack the recipient’s healthy tissues. That made a close HLA match one of the central factors in determining whether a patient could move forward with transplantation.

PTCy changed that equation by selectively eliminating highly reactive immune cells after transplantation, helping promote donor-cell acceptance while reducing the risk of severe GVHD.

That advance has allowed transplant physicians to reconsider how much donor mismatch can be safely tolerated, particularly when a fully matched donor is unavailable or impractical.

“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,” said Jimenez Jimenez.

The study analyzed outcomes from the ACCESS trial, a multicenter phase 2 clinical trial sponsored by the National Marrow Donor Program and conducted through the Center for International Blood and Marrow Transplant Research. Researchers evaluated 268 adults undergoing allogeneic hematopoietic cell transplantation using peripheral blood stem cells from mismatched unrelated donors. All patients received PTCy to help prevent graft-versus-host disease, or GVHD, one of the most serious complications following transplantation.

Earlier ACCESS findings showed favorable outcomes using partially matched unrelated donors. The new analysis examined patients receiving grafts with even greater mismatch, most often donors matched at six of eight key HLA markers.

The results were encouraging. One year after transplantation, overall survival reached 85.6% among recipients of the more mismatched donor grafts and 78.6% among recipients of 7/8 matched grafts. Rates of severe acute and chronic GVHD remained relatively low in both groups, while relapse rates and non-relapse mortality were also favorable.

Investigators emphasize that the exploratory analyses were not designed to prove equivalence between donor groups, but the findings suggest carefully selected mismatched donors may be viable for many patients.

The findings have already translated into clinical practice at Sylvester. Jimenez Jimenez and colleagues have helped lead efforts that expanded the use of mismatched unrelated donor grafts, and today mismatched unrelated donors represent the primary donor source for allogeneic hematopoietic cell transplantation at Sylvester. The shift underscores how directly advances in donor selection and GVHD prevention have moved from clinical research into patient care.

“This work adds to a growing body of evidence that we can expand donor options while still maintaining the outcomes patients and physicians expect from modern transplantation,” said Jimenez Jimenez.

Traditionally, donor selection focused heavily on the number of matching HLA markers. Today, physicians increasingly consider other characteristics that may influence outcomes. In the ACCESS trial, all donors were between the ages of 18 and 35, allowing researchers to evaluate a uniformly young donor population. Prior research has shown that younger donor age can be an important predictor of transplant success.

The study’s authors note that selected younger donors with greater HLA mismatches may be a reasonable option when more closely matched donors are unavailable or impractical.

The researchers caution that longer follow-up is needed to understand long-term survival, relapse and chronic GVHD outcomes. Because donor assignments were not randomized, the study was designed to generate hypotheses and inform future research rather than provide definitive comparisons between donor groups.

Still, the results point toward an important shift. Rather than viewing donor matching as a rigid set of rules, transplant physicians are building a broader picture of what makes the best donor for each patient. The findings suggest the pool of potential donors may be larger than previously recognized, creating new possibilities for patients who need a stem cell transplant.

“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,” said Jimenez Jimenez.

Read more about Sylvester’s efforts to advance cancer research through big data on the InventUM blog and follow @SylvesterCancer on X for the latest news on its research and care.

Publication: Blood Advances

Article Title: “Outcomes after 7/8 and <7/8 mismatched unrelated donor PBSC transplantation with PTCy: results from the ACCESS trial”

Authors: A complete list of authors is available in the paper.

DOI: 10.1182/bloodadvances.2026021081

Funding/Disclosures: Funding and disclosures are included in the article.