Study Reveals Promising Outcomes for Mismatched Blood Transplants

A recent study presented at the American Society of Hematology (ASH) annual meeting indicates that stem-cell transplants utilizing mismatched unrelated donors (MMUDs) can achieve survival rates comparable to those involving better-matched donors. Patients receiving transplants with less than a single human leukocyte antigen (HLA) locus match, defined as <7/8, demonstrated a one-year survival rate of 85.6%, compared to 78.6% for those with better-matched cells. This finding suggests a substantial opportunity to broaden the donor pool for patients with hematologic malignancies.

The study’s lead author, Antonio Jimenez Jimenez, MD, from the University of Miami Sylvester Comprehensive Cancer Center, noted that rates of graft-versus-host disease (GVHD), graft failure, relapse, and non-relapse mortality were not significantly different between the two groups. This analysis was part of the ACCESS study, which included adult patients requiring hematopoietic cell transplants, who were matched with donors having 4/8 to 7/8 HLA compatibility.

Patients in the <7/8 group were generally younger, averaging 57.4 years, compared to 63.3 years in the better-matched group. Importantly, nearly two-thirds of the <7/8 patients identified as racial or ethnic minorities, while the 7/8 cohort comprised 46.4% minorities. Acute myeloid leukemia (AML) was the most prevalent diagnosis in both groups, affecting 44.8% of the 7/8 patients and 55.3% of those with <7/8 matches.

Implications for Donor Accessibility

Jimenez Jimenez emphasized the implications of these findings for donor accessibility, stating, “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.” He explained that registry data indicated all patients without an 8/8 donor match had several available <7/8 donors, highlighting the potential for expanding the donor pool significantly. The importance of this expanded donor pool was echoed by Wendy Stock, MD, from the University of Chicago. She remarked, “Just seeing these data with really excellent outcomes is extremely encouraging. Even though we say we have a donor for everybody, we don’t, unless we expand the donor pool.” Stock further noted that the use of PTCy facilitates this expansion, offering hope to patients facing relapses.

While acknowledging that PTCy has transformative potential, Stock cautioned about its toxicity, particularly in older patients. “It takes some getting used to, but many centers around the world are now very attuned to it,” she stated. The ongoing OPTIMIZE trial aims to examine whether lower doses of PTCy can maintain effective transplant outcomes while reducing toxicity.

Context of Historical Data

Jimenez Jimenez contextualized these findings by referencing historical data, which indicated that survival rates for HLA-mismatched transplants were significantly lower under standard protocols. For example, one notable study reported a 63% one-year overall survival rate for 8/8 matched donors, decreasing to 52% for 7/8 matches and dropping further to 39% for 6/8 matches.

The ACCESS study revealed that the <7/8 MMUD transplantation met its primary objective of non-inferiority compared to 7/8 transplants. Secondary outcomes at one year indicated that <7/8 matches performed at least as well as their better-matched counterparts in various metrics, including GVHD-free and relapse-free survival, as well as rates of acute GVHD. Looking forward, the findings indicate a promising avenue for expanding donor options for patients lacking ideal matches. The ability to consider a broader range of donors could significantly enhance treatment accessibility and equity, particularly for underrepresented populations. In summary, the research underscores the evolving landscape of stem-cell transplantation, showcasing the potential for mismatched unrelated donors to provide comparable outcomes. As ongoing trials like OPTIMIZE explore ways to mitigate toxicity while preserving efficacy, the future appears increasingly optimistic for patients in need of transplants.