Upfront Donor Assessment Improves Transplant Survival for High-Risk Patients

Stephanie Lee, MD, MPH, professor and associate director, Clinical Research Division, Fred Hutchinson Cancer Center, discusses a study published in the Journal of Clinical Oncology assessing how to improve outcomes for patients undergoing bone marrow transplantation.

Historical research has long indicated a disparity in outcomes for patients requiring an allogeneic hematopoietic stem cell transplant (AHSCT) who face difficulties in securing a suitable donor. Studies have consistently shown that this patient population, often due to challenges in identifying a match, experiences worse overall outcomes. Tragically, some individuals may never even make it to the transplant stage.

The study in question was specifically designed to address this challenge by investigating whether an up-front, risk-stratified approach to donor searching could improve the prognosis for these high-risk patients. The central premise was to use preexisting knowledge about the likelihood of finding a suitable donor to direct the search strategy from the moment a patient is determined to need a transplant.

National donor program research and other scientific inquiry have established that certain human leukocyte antigen (HLA) types and other specific patient characteristics are strong predictors of donor-search difficulty. Therefore, clinicians often know that a patient will have a significantly challenging time finding a fully matched unrelated donor (MUD).

The core hypothesis of this study was that for these difficult-to-match patients, prolonged searching for a MUD would be futile and detrimental to survival. Instead, the strategy was to advocate for a rapid pivot to an alternative donor source—such as a haploidentical (half-matched) donor or cord blood—to expedite the patient's journey to the actual transplant procedure. The quicker a patient can receive the necessary transplant, the better their chances of survival were hypothesized to be.

To test this hypothesis, the researchers implemented a biologic assignment study. Patients determined to be very likely to find a matched unrelated donor were placed on the standard protocol. This involved the typical, comprehensive search process for a MUD, which historical data confirm is highly successful. The study noted that 94% of this low-risk group ultimately secured a MUD.

In contrast, patients assessed as very unlikely to find a suitable MUD were immediately directed to an alternative donor pathway. This assignment encouraged physicians to quickly move past a protracted MUD search and proceed with an alternative transplant option as soon as medically feasible. The primary objective of the entire study was then to compare the overall survival of these 2 distinct populations—the standard MUD search group vs the rapid alternative donor group—to determine if the preemptive, rapid-pivot strategy mitigated the historical survival disadvantage for difficult-to-match patients. This approach aimed to demonstrate that strategic intervention in the donor search process can translate into a tangible improvement in patient survival outcomes.

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