ASH 2025 More HLA mismatches possible without poorer transplant outcomes

MedNet.nl: The prospective ACCESS study shows that allogeneic hematopoietic stem cell transplantations (HSCTs) from donors with 2 or more HLA mismatches do not adversely affect 1-year survival when post-transplant cyclophosphamide (PTCy) is used as prophylaxis against graft-versus-host disease (GVHD).

Allogeneic HSCT remains difficult to access for many patients, particularly those of non-European descent, due to the limited number of fully matched unrelated donors (URDs). The outcomes of transplants with 1 HLA mismatch (7 out of 8 HLA matches) are acceptable, but historically, transplants with at least 2 HLA mismatches have been associated with poorer survival and higher toxicity. Post-transplant cyclophosphamide (PTCy) has significantly improved outcomes in transplants with mismatched unrelated donors (MMUDs). Whether the degree of HLA disparity between donor and recipient remains prognostic when using PTCy was unknown until now.

ACCESS included 268 adult patients who received HSCT from an MMUD: 85 had at least 2 HLA mismatches and 183 had 1 HLA mismatch. The median age of the donors was 25 years. In the group with 2 or more HLA mismatches, the majority received myeloablative conditioning with fludarabine/melphalan or busulfan/fludarabine. In this group, 61% identified themselves as non-European.

One year after transplantation, overall survival was 86% in the group with at least 2 HLA mismatches, versus 79% in the group with 1 mismatch. The rates of non-relapse mortality (NRM), relapses, and acute and chronic GVHD were comparable in both groups. One-year GVHD-free and relapse-free survival (GRFS) was also comparable (55 vs 51%). Primary graft failure was rare and limited to patients who received less intensive conditioning.

The results show that PTCy-based GVHD prophylaxis makes it safe to use MMUDs with 4–6 of the 8 HLA matches, which could significantly increase access to suitable donors, especially for patients of non-European descent.

Al Malki MM, 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. ASH Annual Meeting & Exhibition, abstract 936.

This article was originally published in Dutch on MedNet.nl