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Younger mismatched donors with PTCy may improve HCT outcomes over older matched donors for AML

June 2024

Researchers from the Acute Leukemia Working Party (ALWP) of the EBMT examined optimal donor selection criteria in the era of post-transplant cyclophosphamide (PTCy), a key strategy for preventing graft-versus-host disease (GVHD) in hematopoietic cell transplant (HCT). The research focuses on whether younger mismatched unrelated donors (MMUD) might offer advantages over fully matched unrelated donors (MUD). Results suggest that younger MMUDs may improve transplant outcomes when compared with older MUDs for patients with acute myeloid leukemia (AML), calling for a shift in donor selection practices that prioritize HLA matching.

Download a PDF to the study highlights and citation here

Background

PTCy has broadened the pool of potential donors in HCT, enabling more frequent use of MMUD while still achieving successful outcomes. Historically, HLA compatibility has been the primary criterion for donor selection, with other factors like donor age, CMV status and sex being secondary. This study was conducted to reassess these criteria, particularly in light of the expanded donor options made possible by PTCy.

Methods

This retrospective, registry-based study utilized data from the EBMT database. The study included 1,011 adult patients (median age 54 years) with AML in first or second complete remission. These patients underwent their first allogeneic HCT using unmanipulated peripheral blood stem cells and PTCy as GVHD prevention between January 2010 and December 2021. Donors were either MUD (10/10 fully HLA matched) or 9/10 MMUD.

Results

The study's primary endpoint was leukemia-free survival (LFS), with secondary endpoints including overall survival (OS), GVHD-free and relapse-free survival (GRFS), and rates of disease relapse and non-relapse mortality (NRM). The results showed no significant differences in these outcomes between patients receiving transplants from 10/10 MUDs versus 9/10 MMUDs. Likewise, no significant differences were observed when comparing 8/8 MUDs to 7/8 MMUDs, even when considering HLA-DPB1 mismatches or peptide binding motif mismatches.
Notably, the study revealed that donor age had a significant impact on transplant outcomes. Donors older than 30 years were associated with worse relapse rates, LFS, OS and GRFS. In contrast, younger donors (under 30 years) were linked to better survival outcomes. Additionally, the use of CMV-negative donors for CMV-negative recipients was associated with improved LFS.

Key takeaways

This study suggests that in the context of PTCy-based HCT for AML, donor age may be a more crucial factor than HLA matching in determining transplant success. Younger donors, specifically those under 30 years, significantly improved survival outcomes, which may prompt a reconsideration of current donor selection guidelines that prioritize HLA compatibility. These findings warrant further evaluation in other patient populations.

Figure

This figure shows adjusted LFS and OS post-HCT by donor age.

Two line graphs displaying Adjusted LFS vs Adjusted OS
Sanz J, et al., published in Blood