Study Reveals New Hope for Mismatched Blood Cell Transplants

Research presented at the American Society of Hematology (ASH) annual meeting in Orlando indicates that stem-cell transplants using mismatched unrelated donors (MMUDs) may offer comparable survival rates to those from better-matched donors. Patients receiving transplants with less than seven out of eight human leukocyte antigen (HLA) matches achieved a one-year survival rate of 85.6%, while those with better-matched donors had a rate of 78.6%. This finding suggests a significant opportunity to widen the donor pool for patients requiring hematopoietic cell transplants.

The study, led by Antonio Jimenez Jimenez, MD, of the University of Miami Sylvester Comprehensive Cancer Center, highlights the potential for expanding donor access through post-transplant cyclophosphamide (PTCy), a strategy that appears to mitigate complications typically associated with mismatched transplants. Jimenez Jimenez stated, “We have shown that outcomes with less than seven out of eight grafts, using PTCy, appear to be comparable to seven out of eight matches.”

Expanding the Donor Pool

The implications of these findings are profound. Jimenez Jimenez’s analysis of registry data encompassing over 2,400 patients revealed that none had access to an 8/8 donor match. Instead, all patients had several options within the <7/8 donor pool. This access could lead to increased transplant opportunities for patients, particularly among racial and ethnic minorities who have historically faced challenges in finding suitable donors. During the ASH press briefing, Wendy Stock, MD, from the University of Chicago, emphasized the importance of expanding the donor pool, stating, “Just seeing these data with really excellent outcomes is extremely encouraging. Because even though we say that we have a donor for everybody, we don’t, unless we expand the donor pool.” She noted that the realization of transplants being an option may promote patient willingness to undergo procedures, especially when a good donor is identified.

The study’s findings are based on data from the ACCESS study, which enrolled adult patients with hematologic malignancies who required a transplant. Participants had a hematopoietic cell transplant comorbidity index of 0-4 and reasonable performance status. Patients with suitable 8/8 HLA-matched donors were excluded. The analysis compared patient outcomes based on <7/8 matching, showing that they performed at least as well as those with <7/8 matches across various metrics, including graft-versus-host disease (GVHD) and non-relapse mortality.

Comparative Outcomes and Future Directions

The results from this study indicate that <7/8 MMUD transplantation could open doors for many patients in need. Specifically, the one-year overall survival rates for <7/8 matches showed a trend toward better outcomes than those for 7/8 matches. The data on secondary outcomes, including rates of acute GVHD and primary graft failure, were also promising, supporting the efficacy of using PTCy as a prophylactic measure.

Despite these advances, challenges remain. Stock acknowledged that while PTCy has been transformative, its toxicity cannot be overlooked. “It takes some getting used to, but many centers around the world now are very attuned to it,” she remarked. Current research is also focused on determining whether lower doses of PTCy could further reduce toxicity without compromising efficacy.

To this end, the ongoing OPTIMIZE trial, led by Jeff Auletta, MD, aims to explore the impact of reducing the typical PTCy dose by half. Auletta noted that approximately 70% of patients experienced grades II-V infections with the standard PTCy regimen, underscoring the need to balance effective treatment with patient safety.

The potential to increase access to transplants through <7/8 mismatched donors represents a significant shift in the landscape of hematopoietic cell transplantation. As research continues to evolve, the hope is that these findings will lead to broader donor availability, improving outcomes for patients worldwide.