Protective regimen allows successful stem cell transplant even without close genetic match between donor and recipient

(Press-News.org) (ORLANDO, Dec. 6, 2025) A new study shows that giving the chemotherapy drug cyclophosphamide after allogeneic hematopoietic cell transplantation, a curative treatment for common types of blood cancer, can make the procedure safe and effective even when donors and recipients are unrelated and have extensive genetic mismatches. Historically, genetic compatibility has played a primary role in identifying matched donors; these results suggest that many patients who need a transplant could now have access to a much broader pool of potential donors and expect outcomes comparable to those from fully matched donors.

The study found that one-year survival was similar whether patients received transplants with more or less extensive genetic mismatches. Rates of graft-versus-host disease (GVHD), a complication in which donor cells attack the recipient’s own cells, were also comparable.

“With a post-transplant cyclophosphamide-based GVHD prevention strategy, outcomes following mismatched unrelated donor transplant are similar to those achieved with matched donors,” said senior author Antonio Jimenez-Jimenez, MD, associate professor of medicine in the division of transplantation & cellular therapy at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine. “This allows us to find donors for virtually everyone, regardless of their ancestry. Roughly 99% of patients will now have access to a suitable donor on international registries.”

Donor-recipient compatibility has long been assessed by counting how many human leukocyte antigens (HLA) markers a donor and recipient share. These markers encode proteins that serve as immune system receptors on cell surfaces. Matching eight HLA markers has historically produced the best results, whereas having fewer matched markers has been associated with lower survival and higher rates of GVHD.

Finding a donor with close HLA matching is especially challenging for people of non-European ancestry; for example, a Black patient’s likelihood of finding a fully matched donor is just 29%, compared with 89% among non-Hispanic white patients.

Previous studies have shown that giving cyclophosphamide after transplant can improve outcomes when donors and recipients are related but have HLA mismatches, and the same group of investigators has reported encouraging results using bone marrow grafts. This new study is the largest to evaluate the approach in unrelated donors with only four to seven of eight matched HLA markers, using peripheral hematopoietic cell grafts. Peripheral hematopoietic cell grafts are the most common source for hematopoietic cell transplantation and use an outpatient collection process akin to a blood donation.

Among the 268 adult participants, 183 had seven matched HLA markers with their donors, and 85 had four to six. At one year, 79% of the seven-match group and 86% of the four-to-six match group were alive, the study’s primary endpoint. Rates of GVHD-free, relapse-free survival (51% and 55%), relapse (17% and 23%), and non-relapse mortality (14% and 8%) were also similar.

The results suggest that when selecting hematopoietic cell donors, doctors may be able to broaden the acceptable range of HLA matching – greatly expanding the pool of potential donors for each patient – and place greater emphasis on other factors known to influence outcomes, such as younger donor age. “This allows us to try to optimize other donor characteristics beyond just HLA matching,” said Dr. Jimenez-Jimenez.

The results were comparable to those reported by the same investigators in a previous study that used bone marrow grafts for similarly mismatched unrelated donor transplants, suggesting that peripheral blood grafts can be safely and effectively used in this setting. “This makes transplantation much more accessible and easier for patients, and even safer for donors,” said Dr. Jimenez-Jimenez.

The two study groups had comparable and relatively low rates of GVHD. Acute grade 2-4 GVHD occurred in 39% of patients with seven of eight matched markers and 34% of those with four to six matched markers at six months. Rates of moderate-to-severe chronic GVHD at one year were 11% and 8%, respectively.

Patients with fewer matched markers had a slightly higher rate of primary graft failure, meaning that the transplanted cells did not begin producing healthy blood cells. This occurred in 3% of recipients with seven matched alleles and 7% of those with four to six matches, and was limited to older adults who received reduced intensity conditioning. Researchers plan further analyses to better understand and prevent graft failure in this subgroup.

Dr. Jimenez-Jimenez noted that the study was not a randomized trial and that larger studies will be important to confirm these findings. Several related efforts are already underway, including a companion study of pediatric bone marrow transplant recipients and a trial focused on refining the dosing of this cyclophosphamide-based GVHD prevention strategy to reduce toxicity while maintaining its benefits. 

Antonio Jimenez-Jimenez, MD, of the University of Miami School of Medicine, will present this study on Monday, December 8, 2025, at 4:00 p.m. Eastern time in W331 of the Orange County Convention Center.

###

The American Society of Hematology (ASH) (hematology.org) is the world’s largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. Since 1958, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. Join the #Fight4Hematology by visiting hematology.org/fight4hematology.

The Blood journals (https://ashpublications.org/journals) are the premier source for basic, translational, and clinical hematologic research. The Blood journals publish more peer-reviewed hematology research than any other academic journals worldwide.

END