Results from the ACCESS (Allogeneic Cell Transplantation Clinical Evaluation of Stem Cell Sources) study, published in the Journal of Clinical Oncology, demonstrate that post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis enables safe and effective hematopoietic cell transplantation from mismatched unrelated donors (MMUD), significantly expanding access to curative therapy for patients with blood cancers.
The multicenter Phase II clinical trial, sponsored by NMDP and conducted by CIBMTR (Center for International Blood and Marrow Transplant Research), enrolled 145 adult patients with high-risk hematologic malignancies across 21 U.S. transplant centers. Notably, 59% of participants self-identified as members of underrepresented racial or ethnic groups, addressing a critical gap in transplant accessibility.
Strong Survival Outcomes Across Conditioning Regimens
The study evaluated outcomes in two conditioning intensity groups—myeloablative (MAC) and reduced-intensity/nonmyeloablative (RIC/NMA)—and found no significant difference in overall survival between patients with 7/8 HLA-matched donors and those with fewer than 7/8 matches. The one-year overall survival was 83.8% for MAC recipients and 78.6% for RIC/NMA recipients, outcomes that were comparable to or better than historical 8/8 matched donor benchmarks of 75%.
"These study results are a major step forward in making allogeneic peripheral blood stem cell transplantation more accessible for all patients who need a lifesaving procedure," said Monzr M. Al Malki, M.D., Professor, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope and ACCESS study co-chair. "By demonstrating that mismatched unrelated donors can be used safely and effectively, we are opening the door to curative therapy for patients who historically had limited or no donor options."
Low GVHD Rates with PTCy Prophylaxis
Participants received peripheral blood stem cell grafts from MMUDs and were treated with a standardized PTCy-based GVHD prophylaxis regimen. The study observed remarkably low rates of severe GVHD, with grade III-IV acute GVHD at six months occurring in only 8% of MAC patients and 10% of RIC/NMA patients. Severe chronic GVHD at 12 months was observed in only 3% of MAC patients and 4% of RIC/NMA patients.
Addressing Donor Disparities
The research addresses a critical healthcare disparity, as finding an available matched, unrelated donor on international registries has been historically limited for patients with ethnically diverse ancestry. Donor availability ranges from as low as 29% for Black or African American patients and 48% for Latino and Hispanic patients, compared to 79% for non-Hispanic White patients.
The pool of study participants included a high representation of socially vulnerable populations, with many patients reporting financial hardship and reduced physical function at baseline, highlighting the real-world applicability of these findings.
Expanding Research Pipeline
ACCESS builds upon findings from the first Donor for All trial, the groundbreaking NMDP-sponsored 15-MMUD study, which showed that PTCy was effective in decreasing risk for GVHD in adults with hematologic malignancies receiving bone marrow transplants from MMUDs. While ACCESS is closed to further enrollment, pediatric results are forthcoming next year.
The research program continues with the OPTIMIZE trial, which is currently enrolling and evaluating whether a reduced dose of PTCy will safely and effectively prevent GVHD while reducing infection risk in patients with hematologic malignancies receiving peripheral blood stem cell transplants from MMUDs. The ACCELERATE trial will open to accrual this summer to further reduce the risk of GVHD and other post-transplant complications.
"Our Donor for All research is transforming cell therapy as well as redefining donor eligibility and transplant accessibility – helping close the donor gap and extend curative therapies to every patient who needs a life-saving transplant," said Steven Devine, MD, chief medical officer, NMDP, and senior scientific director, CIBMTR, and a senior author of the study.
The findings lay the groundwork for future Phase III trials comparing MMUD transplantation to other alternative donor strategies, potentially revolutionizing access to curative stem cell transplantation for blood cancer patients worldwide.
