MIAMI, FLORIDA (June 26, 2025) – Blood cancer patients who may have previously struggled to find a donor for transplantation now have more options.
A new study shows that patients achieve good outcomes with a partial match drawn from the national public registry of donors when they are treated with the immune-suppressing drug cyclophosphamide. Survival rates at one year were on par with rates seen in other studies with fully matched donors.
These findings should expand the donor pool for patients who have difficulty finding a full match, said Antonio Jimenez Jimenez, M.D. , senior author of the study and a physician-scientist at Sylvester Comprehensive Cancer Center , part of the University of Miami Miller School of Medicine.
Results from the phase 2 nonrandomized trial were published in the Journal of Clinical Oncology .
"Outcomes were comparable to fully matched donors, which means your pool of potential donors is now huge," said Jimenez Jimenez. "Not only can you now offer every patient a transplant, but you can also optimize other factors when looking for a donor."
A Shift in Thinking
Physicians often turn to the National Marrow Donor Program (NMDP) registry when a matched sibling donor is not available. The chance that a sibling is a full genetic match is approximately 25% for patients with one or more siblings. About half of siblings are haploidentical, or half-matched, donors.
Jimenez Jimenez posted about the new study on social media, in a message directed to other oncologists.
"If you're still hesitating to offer an unrelated transplant without an 8/8 match, this study should shift that thinking," he said in the post. "It's not about settling for a second-best option. It's about expanding access to hematopoietic cell transplantation without lowering the bar."
Jimenez Jimenez was chair of the 21-center study, along with Monzr M. Al Malki, M.D., at City of Hope National Medical Center. The trial was sponsored by NMDP and conducted by CIBMTR (Center for International Blood and Marrow Transplant Research (CIBMTR). NMDP operates the U.S. registry of volunteer donors, providing access to over 42 million potential donors worldwide.
Partial Matches, Favorable Outcomes
A matched donor has a fully compatible set of immune system proteins on their cells, called HLA markers. Historically, a partial match raised the risk of immune attack by the donor cells, resulting in a potentially deadly condition called graft-versus-host disease.
The new study found that cyclophosphamide eased this risk when combined with a mixture of other immune-suppressing agents after transplantation.
The researchers reported on 145 adult patients who received transplantation using peripheral blood stem cells, which has largely supplanted bone marrow as a donor source. They were prepared for transplantation using standard regimens, either reduced-intensity or nonmyeloablative (RIC/NMA) conditioning, typically used for older frailer patients, or myeloablative conditioning (MAC). None of the patients had a fully matched family member or unrelated donor available.
All donors were sourced and graft collection facilitated by the NMDP. The vast majority of donors matched at 6/8 or 7/8 markers. All patients received cyclophosphamide to prevent GVHD.
Patients showed overall high one-year survival rates, at 78.6% for RIC and 83.8% for MAC. They also showed low rates of moderate-to-severe chronic GVHD, at 8.6% for RIC/NMA and 10.3% for MAC. What's more, patients who had a match lower than 7/8 showed similar outcomes to patients with a higher match.
These data are comparable to those from prior studies with fully matched patients treated with cyclophosphamide, including a study where RIC/NMA patients received the same post-treatment drug mixture .
The findings also align with a previous smaller trial of cyclophosphamide by the researchers, on mismatched patients receiving bone marrow instead of stem cell transplantation.
The researchers are still collecting and analyzing data on longer-term outcomes, additional enrolled patients and a cohort of pediatric patients. A separate clinical trial is testing a lower dose of cyclophosphamide, which can have side effects such as increased risk of infection. Another planned study will combine cyclophosphamide with a different mixture of drugs.
Born of Necessity
While about 70% of patients from well-represented backgrounds can find a full match in the NMDP registry, only a fraction of others can. Some populations have even worse odds.
"This trial was born of necessity," said Jimenez Jimenez, who presented interim findings from the trial last year at the annual meeting of the European Hematology Association (EHA). "We partnered with the NMDP/CIBMTR to offer this option to patients while advancing the science. It also built on the strengths of Sylvester's transplant program and helped further elevate its standing. We are now recognized globally."
