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Specific Class I HLA Supertypes but Not HLA Zygosity or Expression Are Associated with Outcomes following HLA-Matched Allogeneic Hematopoietic Cell Transplant: HLA Supertypes Impact Allogeneic HCT Outcomes. Transplant Cell Ther 2021 02;27(2):142.e1-142.e11

Date

10/15/2020

Pubmed ID

33053450

Pubmed Central ID

PMC8015676

DOI

10.1016/j.bbmt.2020.10.010

Scopus ID

2-s2.0-85098109122   1 Citation

Abstract

Maximizing the probability of antigen presentation to T cells through diversity in HLAs can enhance immune responsiveness and translate into improved clinical outcomes, as evidenced by the association of heterozygosity and supertypes at HLA class I loci with improved survival in patients with advanced solid tumors treated with immune checkpoint inhibitors. We investigated the impact of HLA heterozygosity, supertypes, and surface expression on outcomes in adult and pediatric patients with acute myeloid leukemia (AML), myelodysplastic syndrome, acute lymphoblastic leukemia, and non-Hodgkin lymphoma who underwent 8/8 HLA-matched, T cell replete, unrelated, allogeneic hematopoietic cell transplant (HCT) from 2000 to 2015 using patient data reported to the Center for International Blood and Marrow Transplant Research. HLA class I heterozygosity and HLA expression were not associated with overall survival, relapse, transplant-related mortality (TRM), disease-free survival (DFS), and acute graft-versus-host disease following HCT. The HLA-B62 supertype was associated with decreased TRM in the entire patient cohort (hazard ratio [HR], 0.79; 95% CI, 0.69 to 0.90; P = .00053). The HLA-B27 supertype was associated with worse DFS in patients with AML (HR = 1.21; 95% CI, 1.10 to 1.32; P = .00005). These findings suggest that the survival benefit of HLA heterozygosity seen in solid tumor patients receiving immune checkpoint inhibitors does not extend to patients undergoing allogeneic HCT. Certain HLA supertypes, however, are associated with TRM and DFS, suggesting that similarities in peptide presentation between supertype members play a role in these outcomes. Beyond implications for prognosis following HCT, these findings support the further investigation of these HLA supertypes and the specific immune peptides important for transplant outcomes.

Author List

Camacho-Bydume C, Wang T, Sees JA, Fernandez-Viña M, Abid MB, Askar M, Beitinjaneh A, Brown V, Castillo P, Chhabra S, Gadalla SM, Hsu JM, Kamoun M, Lazaryan A, Nishihori T, Page K, Schetelig J, Fleischhauer K, Marsh SGE, Paczesny S, Spellman SR, Lee SJ, Hsu KC

Authors

Muhammad Bilal Abid MD Assistant Professor in the Medicine department at Medical College of Wisconsin
Saurabh Chhabra MD Associate Professor in the Medicine department at Medical College of Wisconsin
Kristin Page MD, MHS, MEd Associate Professor in the Pediatrics department at Medical College of Wisconsin
Tao Wang PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adult
Child
Graft vs Host Disease
HLA Antigens
Hematopoietic Stem Cell Transplantation
Humans
Myelodysplastic Syndromes
Unrelated Donors