Original published date: 8/29/2024

Little red dots on her arms: Something that seemed so small turned out to be the first sign that Johanna had a high-risk form of a blood cancer called acute lymphoblastic leukemia (ALL). To save her life, she needed an allogeneic blood stem cell transplant, which uses cells from a donor.

After they couldn’t find a suitable donor in her family, her doctors quickly began searching for a potential blood stem cell donor on the NMDP Registry^SM.

Doctors use markers found on most cells in the body called human leukocyte antigens (HLA) to match patients and donors. In the past, doctors aimed to find a donor who matched at least eight specific HLA markers—called an 8/8 match or fully matched donor—because a full match was crucial for the best outcomes. Because HLA is inherited, a person is most likely to match a donor of a similar ethnic background. The problem: The registry isn’t diverse enough to ensure every patient finds an 8/8 match.

Johanna, who is Hispanic, didn’t have an 8/8 match on the registry. Until recently, that could have prevented her from having a life-saving transplant.

Now science is changing what’s possible for patients like Johanna.

Johanna enrolled in an NMDP^SM-sponsored clinical trial called ACCESS, which is part of the NMDP Donor for All initiative. Donor for All aims to unlock access to blood stem cell transplant through innovative research using partially matched donors. This will significantly expand options for suitable donors—all while providing outcomes in line with using an 8/8 matched donor.

The ACCESS clinical trial includes two groups of adult patients—both of which have completed enrollment—and one group of pediatric patients that continues to enroll patients. The adult patients receive peripheral blood stem cells (PBSCs) from a partially matched donor (5/8 to 7/8 match level) followed by post-transplant cyclophosphamide (PTCy). Pediatric patients receive bone marrow followed by PTCy.

PTCy is a drug that helps prevent a potentially life-threatening complication after transplant called graft-versus-host disease (GVHD) where the donor’s cells (graft) attack the patient’s healthy cells (host). It’s proving to be a gamechanger in allogeneic blood stem cell transplant.

Early ACCESS clinical trial results from a portion of the adult patients are extremely promising. Presented for the first time at the 2024 American Society of Clinical Oncology (ASCO) annual meeting, the ACCESS study results showed that at one year after transplant, patients had:

• Excellent overall survival (79%)
• Significant GVHD-free, relapse-free survival (GRFS) (51%)
• Low rates of severe acute and chronic GVHD (9%)

The adult patients had blood cancers such as ALL, acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS).

More than half of patients who are part of the full ACCESS clinical trial have ethnically diverse ancestry. This is significant because, in the past, only 20% of those enrolled in transplant clinical trials have had ethnically diverse ancestry.

The ACCESS trial is the second of three Donor for All clinical trials sponsored by NMDP and conducted by CIBMTR^® (Center for International Blood and Marrow Transplant Research^®), a research collaboration between the Medical College of Wisconsin^® and NMDP.

The first, smaller study, known as 15-MMUD, included adult patients who received bone marrow from a partially matched donor and PTCy. The results exceeded expectations, with excellent outcomes up to three years after transplant.

The OPTIMIZE clinical trial opened in late 2023 and is enrolling adult patients. OPTIMIZE aims to understand if patients who receive a lower dose of PTCy and PBSCs from a partially matched donor will have better infection-free survival while still preventing GVHD.

While the clinical trial results are encouraging a question remains: Will using partially matched donors truly make a difference in closing the access gap and equalizing outcomes? NMDP and CIBMTR studies and real-world data point to yes.

Researchers from CIBMTR analyzed the NMDP Registry. They found that the likelihood of a patient finding a suitable donor reaches nearly 100% when HLA match levels ranged from 5/8 to 8/8. This is true for all patients, no matter their ethnic background or the donor’s age (age is a factor in matching because research has shown younger donors are associated with better patient outcomes). At a 7/8 match level alone, patients in all ethnic groups have an 84% or higher likelihood of finding a suitable donor.

A real-world study of adult patients at Montefiore Medical Center in Bronx, New York, confirmed the NMDP analysis. The researchers found that all 241 patients included in the study had at least one potential donor at the 5/8 or 6/8 match levels; 80% had more than 100 potential 5/8 and 6/8 matched donors. The vast majority of patients were ethnically diverse.

When looking at how a patient does after transplant, research from CIBMTR indicates that the difference in outcomes between an 8/8 matched and 7/8 matched unrelated donor transplant is no longer a concern. They found no significant differences in overall survival or GVHD-free, relapse-free survival between the two groups.

For Johanna, enrolling in the groundbreaking ACCESS clinical trial made all the difference. Her transplant team quickly found a suitable partially matched donor.

Johanna received her transplant and had a smooth recovery without complications. She’s back at work and planning her wedding, and she had the chance to meet her donor, Catherine.

As she thinks about Catherine, Johanna says, “Because of her, I’m able to be here longer. I really do see it as a second chance … a second chance at life.”

Explore how the NMDP Donor for All initiative is creating new possibilities for patients worldwide to survive and thrive.