Fernando Barroso Duarte* and Hercules Amorim Mota Segundo* comment on the publication entitled “Interplay between donor age and HLA-DP matching in 10/10 HLA-matched unrelated donor HCT” published in Blood Advances.
* Walter Cantídio University Hospital, Federal University of Ceará, Fortaleza, Brazil
Interplay between donor age and HLA-DP matching in 10/10 HLA-matched unrelated donor HCT
Rohtesh S Mehta, Effie W Petersdorf, Tao Wang, Stephen R. Spellman, Stephanie J Lee. Blood Adv 2024; DOI: 10.1182/bloodadvances.2024013677
In this article, Mehta and colleagues evaluated a public dataset provided by the CIBMTR, which included patients with acute myeloid leukaemia, acute lymphoblastic leukaemia, and myelodysplastic syndrome who underwent 10/10-HLA MUD transplants between 2008 and 2018 (n = 14,147). All patients received GVHD prophylaxis based on calcineurin-inhibitors (CNI). Patients who received post-transplant cyclophosphamide (PTCY) were not included. This population was subdivided based on HLA-DPB1 matching (DP-matched, permissive mismatched, and non-permissive mismatched), according to the TCE model. The age of 35 divided donors into "younger" and "older."
Among those with younger donors, the non-permissive mismatched group had worse overall survival (OS). Older donors with DP-matched or permissive mismatched had significantly lower overall survival, even when compared to younger non-permissive mismatched donors in a direct pairwise comparison. Regarding relapse incidence, younger donors had a lower risk in the presence of a mismatch. DP-matching did not influence this outcome among recipients of older donors. Non-relapse mortality (NRM) was similar between the DP-matched/younger donor group and the permissive mismatched/younger donor group. All other groups had a significantly higher risk of NRM. All DP-mismatched groups had a significantly increased risk of acute GVHD grade II-IV compared to DP-matched/younger donors.
This study provides an important contribution to the selection of unrelated donors. While the importance of considering DP-matching and age is well established, there is no consensus on the relative weight of each factor in decision-making. The authors argue that younger donors should be prioritized over older donors, regardless of DP-matching. When multiple younger donors are available, non-permissive mismatches lead to worse outcomes.
By adding crucial information to the donor selection process, this study prompts us to consider several open questions: Should criteria be hierarchized in donor selection? Do younger mismatched URDs lead to better outcomes than older 10/10-HLA MUDs? Is there a practical applicability of models such as TCE, “core/non-core,” “B-leader,” and “PBM”? Will the findings of this analysis be reproducible in populations receiving PTCY prophylaxis?
Current publications lead us to believe that donor selection sits at the fine line between art and science, where multiple factors must be considered simultaneously: diagnosis, disease status, clinical aspects of the recipient, GVHD prophylaxis, conditioning intensity, donor age and sex, HLA-matching, donor-specific antibodies, ABO and CMV serostatus compatibility. Only data will guide us toward the best selection strategy.