Transplant Patients May Have Same Success with Alternative and Fully Matched Donors

A study by the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) found that patients with hematologic malignancies may be able to undergo hematopoietic cell transplant (HCT) with the same success with an alternative donor as a fully matched blood stem cell donor.^1,2

The goal of the study was to determine whether transplant centers could avoid lengthy, unsuccessful searches for fully matched donors when the search was unlikely to be successful. Instead, alternative donors, who included mismatched unrelated donors (MMUD), haploidentical related donors, and umbilical cord blood, we used. There was no difference in time to transplant and overall survival (OS) at 2 years post evaluability, and investigators found no differences in other transplant clinical outcomes.

The findings support research done by the Donor for All initiative, which worked to eliminate disparities in patients from racially and ethnically diverse backgrounds. For example, a White patient has about a 75% chance of finding a fully matched unrelated donor, compared to just 30% to 40% for patients of other races and ethnicities. The ACCESS trial, part of the initiative, focused on improving the outcomes for partially matched or mismatched stem cell transplantation.³

In an interview with Targeted Oncology, Stephanie Lee, MD, principal study investigator and professor and section head of hematologic malignancies in the Clinical Research Division at Fred Hutch Cancer Center, discussed the findings from the study conducted by BMT CTN.

Targeted Oncology: What was the rationale behind this study, and what unmet needs prompted this line of research?

Stephanie Lee, MD: Historical studies reported that when people who need an allogeneic hematopoietic stem cell transplant have a difficult time finding a donor, they don’t do as well. Some of them never make it to transplant, and in general, that population has worse outcomes overall.

This study was designed to see if adjusting the search based on how likely the patient is to find a matched unrelated donor would actually improve the outcomes of those [patients] who are going to have a difficult time.

We know there are certain HLA types and other characteristics where we’re going to have a difficult time finding a matched donor. So, we hypothesized, if you know that, don’t spend a long time looking for a donor you’re never going to find. Pivot quickly to an alternative mismatched donor and get that [patient] to transplant as soon as you can. This study was a biologic assignment study to test the success of this approach…[and] compare the survival between different groups of patients.

What were the results from the study?

[The primary results] showed that, when you follow this algorithm, the time to get to transplant and the actual success of the transplant was not different. Those [patients] who were likely to find a donor, and overwhelmingly did find a matched unrelated donor, their outcomes are pretty similar to patients who were unlikely to find a matched unrelated donor. Only 9% [of the patients very unlikely to find a matched, unrelated donor] found [one]; everybody else had to use an alternative donor, and yet the outcomes were not different between those 2 populations. We found these results to be very encouraging, because it says that both populations can do very well with transplant, as long as you don’t wait too long and delay things trying to find a matched, unrelated donor that you’re never going to find.

How does this study build upon previous research on the topic of mismatched, unrelated donors?

Traditionally, we’ve wanted to use matched donors - matched sibling donors and matched unrelated donors, because historically, those [patients] had the best outcomes. They had the lowest rates of graft-versus-host disease and transplant-related mortality and the highest disease-free survival rates. We knew that it was important to get a good match for our patients. But with all the research advances using different kinds of donors, and particularly different ways of doing the transplant, we’re seeing equally good results using mismatched, unrelated donors and half-matched family member donors.

I think that’s why we’re seeing these results. By rapidly pivoting to alternative donors, you’re actually not losing much in terms of the success of transplant. This work builds on all of the prior work improving the outcomes of transplant for all kinds of patients using different types of donors.

What do you see as the next steps in this line of research?

I think now that we’ve established that people can do well with alternative donors, the next question is to try to find the best alternative donors among those that are available. Of course, we always want to improve the outcomes for all types of transplants, whether you’re HLA-matched or mismatched with your donor. Now we have a baseline to know that patients who are unlikely to find a matched unrelated donor can still do well with alternative donors—let’s improve upon that.

REFERENCES:

1. Lee SJ, Logan B, Horowitz MM, et al. Primary Results From Blood and Marrow Transplant Clinical Trials Network 1702: Clinical Transplant-Related Long-Term Outcomes of Alternative Donor Allogeneic Transplantation. J Clin Oncol. 0, JCO-25-00206 DOI:10.1200/JCO-25-00206

2. No Difference in Transplant Outcomes Seen for Patients Unlikely to Find a Matched Unrelated Donor When a Donor Search Prognosis Strategy is Used. News Release. NMDP. September 19, 2025. Accessed October 6, 2025. https://tinyurl.com/4vw69s5u

3. NMDP’s ACCESS Trial Results Published in Journal of Clinical Oncology, Demonstrating Strong Outcomes with Mismatched Unrelated Donors in Adult Stem Cell Transplantation. News release. NMDP. June 17, 2025. Accessed October 6, 2025. https://tinyurl.com/y77maybu