ACCESS Study: <7/8 HLA Mismatch Outcomes Comparable to 7/8 with PTCy

The ACCESS trial (NCT04904588) addressed significant barriers to allogeneic hematopoietic cell transplantation (HCT) caused by the limited availability of matched unrelated donors, a challenge that disproportionately affects patients of non-European ancestry. While single-HLA mismatched donors (7/8) generally yield acceptable outcomes, donors with mismatches at ≥2 HLA alleles (<7/8) have historically been associated with prohibitive toxicity and poor survival.This study prospectively evaluated the use of posttransplant cyclophosphamide (PTCy) as graft-vs-host disease (GVHD) prophylaxis to determine if it could mitigate the risks associated with greater HLA disparity.

The analysis comprised 268 adult recipients of peripheral blood stem cell grafts: 85 recipients had <7/8 matches (primarily 6/8), and 183 recipients had 7/8 matches. Notably, the <7/8 cohort was racially and ethnically diverse, with 61% identifying as other than non-Hispanic white. The primary end point measured was 1-year overall survival (OS).

Outcomes at one year demonstrated that high-degree mismatching did not adversely affect patient survival when PTCy was utilized. The <7/8 cohort achieved a 1-year OS of 86%, which was comparable to, and numerically higher than, the 79% observed in the 7/8 cohort. Secondary end points showed similar parity between the 2 groups:

• Relapse: 23% in the <7/8 group vs 17% in the 7/8 group.
• Nonrelapse Mortality (NRM): 8% for <7/8 recipients compared with 14% for 7/8 recipients.
• GVHD-Free Relapse-Free Survival (GRFS): 55% for <7/8 recipients vs 51% for 7/8 recipients.

Furthermore, rates of grade 2 to 4 acute GVHD and chronic GVHD were similar across both cohorts. The authors concluded that outcomes for <7/8 recipients using PTCy are favorable and consistent with 7/8 recipients. These findings support extending donor matching criteria to include 4–6/8 matches, potentially enabling near-universal donor access.

REFERENCE

Al Malki M, Bo-Subait S, Logan B, et al. Mismatching of unrelated donors beyond a single HLA-locus does not adversely impact outcomes at one year following transplantation: Results from the NMDP sponsored ACCESS study. Presented at: 2025 ASH Meeting & Exposition; December 6–9, 2025; Orlando, Florida. Abstract 936.