HLA evolutionary divergence (HED) informs the effect of HLA-B mismatch on outcomes after haploidentical transplantation.

Autor: Solh M; The Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA, USA. msolh@bmtga.com., Aubrey MT; University of Colorado Blood Bank and Clinimmune Laboratory, Aurora, CO, USA., Zhang X; School of Public Health, University of Texas, Houston, TX, USA., Bashey A; The Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA, USA., Freed BM; University of Colorado Blood Bank and Clinimmune Laboratory, Aurora, CO, USA., Roark CL; University of Colorado Blood Bank and Clinimmune Laboratory, Aurora, CO, USA., Bachier-Rdriguez L; The Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA, USA., Morris LE; The Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA, USA., Kent Holland H; The Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA, USA., Solomon SR; The Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA, USA.
Jazyk: angličtina
Zdroj: Bone marrow transplantation [Bone Marrow Transplant] 2024 Oct; Vol. 59 (10), pp. 1433-1439. Date of Electronic Publication: 2024 Jul 31.
DOI: 10.1038/s41409-024-02341-z
Abstrakt: Graft versus tumor relies on tumor-associated antigens (TAAs) that are presented to donor T cells via human leukocyte antigens (HLAs). The HLA evolutionary divergence (HED) between alleles of a single individual can dictate the ability to present TAAs. The impact of HED in haploidentical donor transplantation (HIDT) has not been studied. We studied the effect of HED on transplant outcomes following HIDT. We analyzed 322 consecutive recipient/donor pairs with a median follow-up of 57.2 months. Pairwise divergence of HLA class I and II showed that HLA-B, -DRB1, and -DQB1 contributing most to mean HED. The mean HED was class I 6.85 (HLA-A 7.08, -B 8.24, and -C 5.07), class II 8.58 (HLA-DRB1 10.97, -DQB1 10.06 and -DPB1 4.06). A high HED in class I mismatched recipient/donor haplotype (RD MM) was significant for worse DFS (HR 1.11, p = 0.020), and relapse (HR 1.11, p = 0.02). Also, a high HED in RD MM HLA-B haplotype had worse OS (HR 1.07, p = 0.02), DFS (HR 1.09, p = 0.002), higher relapse (HR 1.10, p = 0.003), and similar NRM to low HED. The multivariate analysis showed that high HED in RD MM HLA-B (≥7.8 vs <7.8) had worse DFS (HR 1.53, p = 0.01), higher relapse (HR 1.61, p = 0.024), and similar NRM and OS.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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