ACCESS Trial Expands Donor Pool and Improves Outcomes for Diverse Transplant Patients

The landscape of hematopoietic stem cell transplantation is undergoing a significant shift, driven by new data that challenge long-held assumptions about donor matching. According to Heather Stefanski, MD, PhD, vice president of CIBMTR and Clinical Services at NMDP, the ACCESS trial (NCT04904588) has demonstrated that mismatched unrelated donors can provide excellent outcomes, effectively opening the door for nearly every patient in need of a life-saving transplant.

In a recent discussion, Stefanski detailed the trial’s background, its "unheard of" demographic diversity, and the impressive survival rates that are set to redefine clinical practice.

Addressing the Racial Disparity in Donor Matching

The genesis of the ACCESS trial was rooted in a statistical reality: the disparity in finding fully matched donors based on a patient’s ethnic background.¹

"The reason that we wanted to do the ACCESS study was because not every patient has a fully matched eight of eight donor on the registry," Stefanski explained. "For example, for [an] African-American [patient], the likelihood of finding an 8/8 [match] is 29%, whereas for a non-Hispanic White [patient], it goes up to 79%."

Historically, patients without a perfect match faced grim options. "If you need to have an 8/8 match or a donor on the registry to have the best outcomes for your transplant, there [are] going to be patients that would not have an 8/8... so then they potentially wouldn't get their life-saving cell therapy," said Stefanski. "And if they had less than 8/8, they wouldn't have great outcomes."

However, the success of posttransplant cyclophosphamide (PTCy) in haploidentical (half-matched family member) transplants prompted researchers to investigate its efficacy in mismatched unrelated donors (MMUD).The goal was to expand the acceptable donor pool.

"If you can go to 7/8s, or even 6/8s, that increases the likelihood of a donor on a registry to 99%," Stefanski noted.

Unprecedented Diversity and Survival Rates

The ACCESS trial enrolled 268 adult patients receiving peripheral blood stem cell transplants from donors with match levels between 4/8 and 7/8. The study utilized PTCy for graft-vs-host disease (GVHD) prophylaxis.²

Stefanski highlighted a unique achievement regarding the trial's demographics. "What we also saw with that trial is that over 50% of the patients were racially or ethnically diverse, and that's unheard of in other clinical trials," she said. "If you need a perfectly matched donor, then it's going to be...80% or more non-Hispanic Whites. So now we allow mismatched, unrelated donors. We're expanding the type of patients that we're having on this trial."

The clinical outcomes matched the inclusivity of the design. At the 1-year mark, overall survival rates were robust.

"For 1-year overall survival, it was 80%... it exceeded 80% for all levels," Stefanski reported. "And then when you look at the less than 7/8s, it was 86%. For 7/8, it was 79%...so really excellent overall survival."

Stefanski also noted favorable toxicity profiles across the board:

• Nonrelapse mortality: 8%
• Relapse: 23%
• Moderate to severe chronic GVHD: Less than 12%

"These rates were similar, and they were similarly favorable between the cohorts, regardless of the conditioning regimen," she added. "Now, going less than 7/8, we're going to be able to accommodate essentially every single patient that needs a transplant."

Changing Clinical Practice

Stefanski believes these findings should immediately impact how clinicians assess transplant candidacy.

"I think sometimes for certain patient populations, there has always been the assumption that if you don't have the perfect match, that you're not a candidate for transplant," she said. "Now showing this data, it's going to show that there [are] excellent outcomes with mismatched, unrelated donors...These patients that potentially would never have been offered this life saving transplant will now be able to undergo transplant."

Next Steps: The Optimize and Accelerate Trials

While the ACCESS trial results are promising, Stefanski emphasized that the research is ongoing, particularly regarding the reduction of adverse effects. The standard dose of PTCy (50 mg/kg) carries risks of cardiac toxicity, hemorrhagic cystitis, and infection.

The NMDP is currently wrapping up the OPTIMIZE trial (NCT06001385), which lowered the PTCy dose to assess the impact on infection-free survival.² Concurrently, they have launched the ACCELERATE trial (NCT06859424}, a platform-based protocol designed to test new combinations.³

"With the ACCELERATE trial, we're going to be using that with posttransplant cyclophosphamide as the backbone," Stefanski explained. The trial will compare a control arm (PTCy at 50 mg/kg) against 2 interventional arms using a lower dose (25 mg/kg) combined with other agents.

The Remaining Frontier: Relapse

Despite advancements in donor matching and GVHD prophylaxis, Stefanski identified relapse as the primary unmet need in the field.

"The biggest unmet need is how to mitigate relapse, because that's still the most common unfortunate complication," she stated. "We've already done great with GVHD...but I think the next frontier is going to be finding ways to prevent relapse from happening."

Reflecting on the trajectory of the field, Stefanski expressed pride in how rapidly the landscape has changed for underserved patients.

"When you think about where the field was...in 2020, we saw the least number of mismatched unrelated donor transplants that we've ever seen...and we're in 2025 and we've never seen more mismatched, unrelated donor transplants," she concluded. "When you look at the patient population that we're serving, it's truly serving patients that had never been served before."

REFERENCES

1. Al Malki M, Bo-Subait S, Logan B, et al. Mismatching of unrelated donors beyond a single HLA-locus does not adversely impact outcomes at one year following transplantation: Results from the NMDP sponsored ACCESS study. Presented at: 2025 ASH Meeting & Exposition; December 6–9, 2025; Orlando, Florida. Abstract 936.

2. HLA-mismatched unrelated donor peripheral blood stem cell transplantation with reduced dose post transplantation cyclophosphamide GvHD prophylaxis (OPTIMIZE). ClinicalTrials.gov. Updated May 29, 2025. Accessed December 9, 2025. https://www.clinicaltrials.gov/study/NCT06001385

3. A platform protocol to investigate post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis in patients with hematologic malignancies undergoing mismatched unrelated donor peripheral blood stem cell transplantation (ACCELERATE). ClinicalTrials.gov. Updated September 10, 2025. Accessed December 9, 2025. https://www.clinicaltrials.gov/study/NCT06859424