Mismatched donor sources may fill an unmet need for patients without fully matched family or unrelated donors
Research presented at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition suggests that mismatched donor sources and transplant strategies supporting mismatched donor hematopoietic cell transplantation (HCT) may fill a need for patients without fully matched (8/8) family or unrelated donor options.
The study showed that most patients who received haploidentical-related donor (HRD) HCT were unlikely to have an 8/8 unrelated donor (URD) but likely to have a single-mismatched (7/8) URD.
BackgroundThe number of HRD HCTs performed in the United States has grown more than fourfold over the last decade. A significant contributor to the growth is the use of post-transplant cyclophosphamide (PTCy) based graft-versus-host disease (GVHD) prevention strategies. This has particularly benefited racially and ethnically diverse patients who often don't have readily available 8/8 matched URDs in the various global registries.
However, not all patients have a suitable or healthy HRD, and many have donor-specific antibodies that can increase the risk of graft rejection and mortality. Recent studies show superior outcomes in certain settings using matched (8/8) or single-mismatched (7/8) URD compared to HRD when receiving PTCy.
This observational study consisted of 8,281 HRD HCT recipients between the ages of 0-87. These patients received HRD HCT for any disease reported to the CIBMTR® (Center for International Blood and Marrow Transplant Research®) from 2013-2020. Those missing HLA (human leukocyte antigen) typing were excluded.
Simulations of a URD search were run on each patient based on high-resolution HLA typing and a search prognosis score calculated to estimate the likelihood of finding a matched or mismatched donor on the Be The Match Registry®.
The growth of HRD HCT over the study period exceeded the likelihood of an 8/8 donor existing in the registry, but the existence of a potential 7/8 URD increased, as shown in Figure 1 below. This demonstrates that haploidentical donors and 7/8 mismatched URDs can provide an alternative to fully matched donors.
The study team then limited the analysis to review adult HRD HCT recipients (n=6,580). The search prognosis score varied by race and ethnicity. Overall, 40-79% of HRD HCT recipients had 5 or more potential 7/8 URDs, increasing the likelihood that a donor would be available at the time of need.
A deeper look into the practices of the 10 largest transplant centers that performed the most adult HRD HCT in the U.S. during the study period showed all except one of the centers had more than 80% of the searches identify at least one 7/8 URD.
An additional simulation of URD existence for adults based on underlying disease showed greater than 83% identified at least one 7/8 URD using the four most common malignant indications: acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, and non-Hodgkin lymphoma.
The study showed that while most U.S. patients undergoing HRD HCT were unlikely to have an 8/8 URD match, they were likely to have 7/8 URD matches. Recent reports have noted similar and, in some cases, superior outcomes with matched or single-mismatched URDs compared to HRDs who received PTCy. While HRD was found to be generally used appropriately, these patients were also likely to have had a 7/8 unrelated donor.
This demonstrates that transplant strategies supporting the use of mismatched donor sources (haploidentical related or mismatched unrelated) can fill an unmet need for patients without a fully matched family or unrelated donor. This further supports the potential to expand access to all patients needing HCT through mismatched unrelated donors. Additionally, data support the feasibility of high-priority clinical trial concepts from the Blood and Marrow Clinical Trials Network (BMT CTN) State of the Science Symposium to further examine the use of mismatched unrelated donor sources.
Fingerson S, et al., ASH poster presentation abstract
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