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
| Autor: | Marcelo Fernandez-Vina, Johannes Schetelig, Jennifer A. Sees, Medhat Askar, Valerie I. Brown, Katharina Fleischhauer, Paul Castillo, Malek Kamoun, Amer Beitinjaneh, Katharine C. Hsu, Muhammad Bilal Abid, Tao Wang, Stephen R. Spellman, Stephanie J. Lee, Shahinaz M. Gadalla, Sophie Paczesny, Saurabh Chhabra, Taiga Nishihori, Aleksandr Lazaryan, Christine Camacho-Bydume, Kristin Page, Steven G.E. Marsh, Jingmei Hsu |
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| Rok vydání: | 2020 |
| Předmět: |
Oncology
Adult medicine.medical_specialty Antigen presentation Medizin Graft vs Host Disease Disease Human leukocyte antigen Article Loss of heterozygosity Immune system HLA Antigens Internal medicine hemic and lymphatic diseases medicine Immunology and Allergy Humans Child Transplantation business.industry Hazard ratio Hematopoietic Stem Cell Transplantation Myeloid leukemia Cell Biology Hematology medicine.disease Lymphoma Myelodysplastic Syndromes Molecular Medicine business Unrelated Donors |
| Zdroj: | Transplant Cell Ther |
| ISSN: | 2666-6367 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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