PTCy Enables Flexibility in Mismatched Donor Transplant

Heather Stefanski, MD, PhD, representing the National Marrow Donor Program, discusses how the ACCESS study (NCT04904588) has fundamentally shifted the traditional understanding of donor matching in stem cell transplantation. For decades, the prevailing clinical dogma preferred an 8/8 human leukocyte antigen (HLA) match as the gold standard for a successful transplant, with 7/8 mismatches being used when no matches could be found.

With the use of post-transplant cyclophosphamide (PTCy), options are expanding. The rapid accrual of patients in this trial prompted the research team to expand the study, particularly within the reduced-intensity conditioning arm. This expansion was driven largely by significant demand from transplant centers eager to provide their patients with access to the PTCy protocol within a structured clinical trial setting.

This increased enrollment allowed researchers to perform a critical comparative analysis between different levels of donor mismatch. The study sought to determine if there were significant differences in outcomes between a 7/8 HLA match and even more disparate matches, such as 6/8 or 5/8. The ability to compare these less than 7/8 matches is vital for patients with rare HLA types who often lack even a single-mismatch option on global registries.

The core finding of this analysis was that there were no substantial differences in clinical outcomes based on the degree of the mismatch when PTCy was employed. This discovery shifts clinical thinking away from the idea that a full match is a prerequisite for a safe and effective transplant. Stefanski notes that these results provide clinicians with the confidence to move beyond the search for an 8/8 or 7/8 donor. If a closely matched donor is unavailable, the data supports the safe use of donors with multiple mismatches.

By demonstrating that PTCy can successfully overcome the biological barriers of HLA disparity, the ACCESS study significantly simplifies the donor selection process. This shift allows for a more efficient and inclusive approach to transplantation, ensuring that the lack of a “perfect” donor no longer prevents a patient from receiving curative therapy. Ultimately, this research provides the evidence needed to move toward a more flexible transplant model where donor availability is no longer the primary limiting factor for patient survival.