Advanced donor matching makes stem cell transplants accessible

Advanced donor matching makes stem cell transplants accessible

For years, the search for a stem cell donor has felt like searching for a rare key — a key that fits a lock with eight intricate tumblers, each representing a genetic marker. For many patients with blood cancer, particularly those from diverse backgrounds, the right key simply did not exist. The door to healing remained closed.

But a new study led by a national, multicenter team that includes Dr. Antonio Jimenez Jimenez, associate professor of medicine in the Division of Transplantation and Cell Therapy at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, suggests that the lockdown itself is changing. Thanks to a protection plan and a new look at donor compatibility, the door to life-saving transplants could be opened for almost everyone.

Jimenez Jimenez is no stranger to this border. As senior author and physician-scientist at Sylvester, he has been at the forefront of research into graft-versus-host disease (GVHD) prophylaxis for years. In fact, he and other researchers demonstrated the feasibility of this strategy with bone marrow transplants in a large multicenter study and presented initial results of the current study at the 2024 European Hematology Association (EHA) Annual Meeting, helping to lay the foundation for this latest advance.

We're rewriting the rules for what's possible with a stem cell transplant. For patients who once faced impossible odds, this research opens the door to hope.”

Antonio Jimenez Jimenez, MD, associate professor of medicine, Division of Transplantation and Cell Therapy, Sylvester Comprehensive Cancer Center

Break the match barrier

Think of the immune system as a strict security team checking IDs at the entrance to the body. For decades, only donors with a near-perfect genetic match – an eight-out-of-eight “pass” – were allowed through. This worked for some, but excluded many others, particularly people of non-European descent. Today, only about 29% of black patients can find a fully matched donor in the registry, compared to 89% of non-Hispanic white patients.

The ACCESS study, funded by the National Marrow Donor Program (NMDP), could rewrite the rules. The research team's latest findings will be presented by Jimenez Jimenez on December 8 at the American Society of Hematology (ASH) 2025 Annual Meeting in Orlando. The study will also be highlighted in a special ASH press conference on December 6 at 8:30 a.m. EST.

Jimenez Jimenez and colleagues found that patients with protective treatment with post-transplant cyclophosphamide (PTCy) can safely receive stem cell transplants from unrelated donors in which two or more HLA markers do not match. In other words: the “key” is no longer so rare.

“By expanding donor matching criteria, we are making transplants accessible to almost everyone, regardless of race,” said Jimenez Jimenez. “This could be a major advance in cancer treatment.”

What the study found

The ACCESS study involved 268 adults with blood cancer. Participants received peripheral blood stem cell transplants from unrelated donors aged 35 years or younger with either seven of eight HLA markers matched (183 patients) or only four to six matched (85 patients).

After one year, the survival rates were almost the same:

• 86 % für diejenigen mit vier bis sechs übereinstimmenden Markern
• 79 % für diejenigen mit sieben übereinstimmenden Markern

Rates of graft-versus-host disease (GVHD) – the immune system's “friendly fire” variant – were also comparable and relatively low. Grade II-IV acute GVHD occurred in 34% of the more dissimilar group and 39% of the less dissimilar group at six months. Chronic moderate to severe GVHD at one year was 8% and 11%, respectively.

Importantly, 61% of the group with greater inequality than others identify as non-Hispanic white.

Why it matters

This research is more than a technical advance – it could be a lifeline. With PTCy-based GVHD prevention, physicians can consider donors with as few as four out of eight HLA matches. The pool of potential donors becomes an ocean, not a pond. For patients who once faced impossible odds, hope may no longer be out of reach.

“We are seeing results that rival those of fully matched donors, even in patients who previously had little chance of finding a donor match,” said Jimenez Jimenez. “This is transformative for our specialty and for our patients.”

The results also allow doctors to look at other donor characteristics, such as: B. prioritizing younger age, which are known to improve transplant outcomes. Science addresses the needs of real people.

Think of cyclophosphamide as a peacemaker, stepping in after the transplant to calm the immune system's overzealous sentinels. By targeting the cells most likely to cause problems, this drug prevents GVHD and helps the new cells settle in as part of the team. The ACCESS study confirms that this approach works even if the donor “ID” does not match perfectly.

“Cyclophosphamide has changed the landscape of transplant and donor utilization trends,” said Jimenez Jimenez. “It allows us to safely use donors that were considered unsuitable just a few years ago.”

Although the results are positive, the study authors note that further research is needed. The ACCESS trial was non-randomized and ongoing studies are investigating optimal dosing and strategies for pediatric patients. Nevertheless, the data suggests that almost 99% of patients could now have access to a suitable donor in international registries.

“We are committed to refining these strategies and ensuring that every patient – ​​regardless of their background – has a chance for a cure,” said Jimenez Jimenez.

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