Improving ACCESS to Stem Cell Transplant for All Patients

In an interview with Targeted Oncology, Antonio Jimenez Jimenez, MD, discussed the NMDP-sponsored ACCESS study (NCT04904588), which is seeking to improve outcomes for partially matched or mismatched stem cell transplantation and bridge the gap in transplant access for ethnically and racially diverse patients.

The likelihood a patient will have an 8/8 HLA-matched, available donor differs greatly depending on the patient's race and ethnicity. Patients who are Black and African American, for example, have a 29% chance of finding an 8/8 HLA-matched donor on the NMDP Registry, while those who are Hispanic have a 48% chance. Comparatively, those who are non-Hispanic White have a 79% chance.¹

“For patients who are ethnically and racially diverse, transplant options are limited,” said Jimenez Jimenez, leader of the Mismatched Allogeneic Transplant Program at Sylvester Comprehensive Cancer Center, University of Miami, in the interview. “So, the idea was an effort to expand transplant access but also improve the outcomes of mismatch transplantation.”

The ACCESS study is part of the NMDP’s Donor for All initiative, which seeks to research and establish approaches for patients to achieve effective, safe transplants through mismatch unrelated donors with similar outcomes to traditional 8/8 matches.²

ACCESS builds upon the previous 15-MMUD study (NCT02793544) and expands upon it with a logistically easier platform utilizing peripheral blood stem cells and including more centers and a more diverse patient population, including a pediatric arm.³

Targeted Oncology: What was the rationale behind ACCESS?

Antonio Jimenez Jimenez, MD: The rationale behind the study is twofold. Number 1, I think the important point was to improve the outcomes of partially matched or mismatched transplantation. These are transplants we have been doing for many years out of necessity and at the expense of higher mortality and high risk with increased graft-vs-host disease and rates of infection. I don’t want to say it was a necessary evil, but it is something that we have to offer to patients with no other donor options. But when we use mismatch grafts, it comes at the expense of increased mortality and morbidity.

[Secondly, the rationale was] to help to bridge the gap in transplant access. For patients who are ethnically and racially diverse, transplant options are limited. We know that for Caucasian patients, the likelihood of finding an 8/8 [HLA match donor] in the registry is close to 80%, but that's [about] 50% for a Hispanic patient and around 20 to 30% for an African-American patient. So, the idea was an effort to expand transplant access but also improve the outcomes of mismatch transplantation.

We started this with our first trial, the 15-MMUD, which was published in [the Journal of Clinical Oncology in 2021]. The idea of ACCESS was to expand it to a more logistically easier platform, which is peripheral blood. We also expanded to many more centers and much more diverse patients. We included a pediatric arm in this group, which has not been presented yet.

Could you give an overview of the study?

ACCESS was a phase 2, multicenter, nonrandomized study. We presented the report of the first 145 patients, but there are additional patients that we are evaluating, and we will be presenting that later. These were patients receiving their first allo[geneic stem cell] transplant for mismatched, unrelated donors, so between 4/8 and 7/8 mismatched, unrelated donors. All of the grafts for the adult cohort were peripheral blood stem cells, and every patient received the same GVHD prophylactic platform, which was [posttransplant cyclophosphamide (PTCy)] on days 3 and 4, tacrolimus, and [mycophenolate mofetil (MMF)]. About half of the patients, roughly, received a myeloablative regimen, and the other half [received] reduced-intensity conditioning.

[There was a] very young donor age. The median donor age was 23 years. We restricted it to 35 [years old as an] upper limit, and very importantly, 59% of patients were non-White or were ethnically diverse. I think this is one of the most important findings of the study in illustrating how it truly expands access to patients that historically have been somehow marginalized from these trials or had limited donor options.

What outcomes did you observe?

The encouraging thing to see was that we have outcomes that were comparable to fully matched donors. One-year survival for the myeloablative conditioning group was over 80%, [and] for the reduced intensity, close to 80%, with very low grades of grades 3 or 4 moderate or severe chronic GVHD. Grade 3 or 4 acute GVHD in the myeloablative conditioning group was a little bit lower, 8%, than in the reduced intensity group, 10%.

Another important finding that I think is worth highlighting was that we find no difference in survival between a single antigen mismatch—7/8—and less than 7/8. I think this finding is very, very key, because when we look at also finding a donor, when we are permissive to higher degrees of mismatch, we could essentially identify a donor for any patient, irrespective of the race and ethnicity. That also allows us to optimize some non-HLA factors, so we can get a little bit pickier. We can choose younger donors, and we can optimize other factors like antibodies, CMV match, ABO match, or whatever we decide for that specific patient. So, we’re expanding access, but we're also choosing potentially the very best donor for that particular patient.

What do you see as next steps from here?

The things that we're trying to explore are improving outcomes further by minimizing toxicity [through the OPTIMIZE study (NCT06001385), sponsored by the Center for International Blood and Marrow Transplant Research]. One of the elements is looking at a lower dose of cyclophosphamide that we hope will be equally protective against rejection and graft-vs-host disease but minimize the infection. We have other research efforts looking at a combination or adjunctive therapy to cyclophosphamide, which is also on the horizon.

It's important to remember that by using cyclophosphamide or some of these novel therapies, we are addressing the biological barrier. But there are many other barriers to accessing transplantation for patients who are ethnically or racially diverse, and many other groups are working very hard on these. But I think this is a very first step, because once you show that these transplants are feasible, safe, and comparable, I think that chips away at some of these other barriers. For example, referral bias—the referring doctors might be more willing to send patients for these kinds of trials or often offer a mismatch.

The other thing we want to emphasize is that if we offer a new alternative that appears to be equally safe and effective, we can move a little bit away from the historical linear search when looking for donors. In the past, what we have always done is go for a fully matched donor. If that fully matched donor is not an option, then we go with a sibling, and then we go with a 7/8. And then if nothing else works, then highly mismatch. I think the problem with this strategy is it takes a long, long time. We want to move away from this linear search and look at things in a more holistic way in which we consider all donor options at the same time if we can anticipate that outcomes are comparable so you don’t miss that window of opportunity to take patients to transplant.

We’re excited, of course, to present data on this larger cohort. We're excited to see what the outcomes are for the pediatric population. And we’re, of course, excited to see how we can optimize these outcomes even more.

REFERENCES:

1. Chowdhury AS, Maiers M, Spellman SR, et al. Existence of HLA-Mismatched Unrelated Donors Closes the Gap in Donor Availability Regardless of Recipient Ancestry. Transplant Cell Ther. 2023 Nov;29(11):686.e1-686.e8. doi: 10.1016/j.jtct.2023.08.014. Epub 2023 Aug 14.

2. NMDP Donor for All. NMDP. Accessed August 12, 2025. https://tinyurl.com/m9dpda86

3. Al Malki MM, Bo-Subait S, Logan B, et al. Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis After Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation. J Clin Oncol. 2025 Jun 16:JCO2500856. doi: 10.1200/JCO-25-00856. Online ahead of print.