Study Shows Mismatched Stem Cell Transplants Can Boost Survival Rates

New research presented at the American Society of Hematology (ASH) annual meeting indicates that stem-cell transplants from mismatched unrelated donors (MMUDs) can achieve comparable 1-year survival rates to those from better-matched donors. This finding suggests a significant opportunity to widen the donor pool for patients in need of hematopoietic cell transplants.

The study, led by Antonio Jimenez Jimenez, MD, of the University of Miami Sylvester Comprehensive Cancer Center, shows that patients receiving transplants with less than a 7 out of 8 human leukocyte antigen (HLA) match experienced a 1-year survival rate of 85.6%, compared to 78.6% for those with better-matched donors. Furthermore, the rates of graft-versus-host disease (GVHD), graft failure, relapse, and non-relapse mortality did not differ significantly between the two groups.

In a separate analysis involving over 2,400 patients who lacked 8/8 donor matches, all participants had access to multiple donors from the <7/8 donor pool. Jimenez Jimenez stated, “We have shown that outcomes with less than seven out of eight grafts, using post-transplant cyclophosphamide (PTCy), appear to be comparable to 7/8 matches.”

The implications of these findings are profound. Expanding the donor pool to include all levels of mismatched donors could facilitate near-universal access to transplants, regardless of race or ethnicity, while optimizing other non-HLA donor factors. This expanded access is crucial, as emphasized by Wendy Stock, MD, of the University of Chicago, who noted that the findings are encouraging in the context of addressing the ongoing challenge of finding suitable donors for all patients.

The study highlights the historical challenges associated with HLA-mismatched transplants, which have often resulted in poor outcomes. Previous research indicated a stark decline in survival rates, with only 63% overall survival for 8/8 matched donors dropping to 39% for 6/8 matches. Jimenez Jimenez’s work aims to shift this narrative by demonstrating that less-than-perfect matches can yield similar outcomes under the right conditions.

The ACCESS study enrolled adult patients with hematologic malignancies who required a transplant and had a donor match ranging from 4/8 to 7/8. Patients with a suitable 8/8 HLA-matched donor were excluded. The analysis involved 278 patients, stratified by conditioning type and match quality. Notably, the <7/8 group was younger and included a higher percentage of racial and ethnic minorities compared to the 7/8 group. The primary objective was to demonstrate non-inferiority of <7/8 MMUD transplants in terms of 1-year overall survival. The results exceeded expectations, showing a trend toward improved overall survival rates for the <7/8 group. Secondary outcomes, such as GVHD-free and relapse-free survival rates, also indicated that <7/8 matches performed at least as well as their better-matched counterparts. The findings were underscored by Jimenez Jimenez’s analysis of global registry data, which revealed that all patients without potential 8/8 matches had access to multiple <7/8 donors. He noted that decreasing the HLA match requirement significantly increases the number of available donors, enhancing access and equity in transplantation. While the study’s results are promising, the use of PTCy, which has been described as a "game changer" in the field, is not without risks. Stock acknowledged its potential but cautioned that it requires careful management due to the associated toxicity, especially in older patients. Ongoing research, including the OPTIMIZE trial, will investigate whether lower doses of PTCy can maintain transplant efficacy while reducing side effects. The OPTIMIZE trial specifically aims to assess the impact of a 50% reduction in PTCy dosage on toxicity and efficacy, with early endpoints focusing on infection-free survival rates. Findings from this trial may further refine the approach to donor matching and post-transplant care, ultimately improving patient outcomes.

As the field of stem cell transplantation evolves, the implications of these findings could reshape the landscape of donor matching, expanding opportunities for many patients who currently face challenges in finding suitable matches. The potential for PTCy to facilitate this change underscores the need for continued research and innovation in transplantation practices.