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The "human leukocyte antigen (HLA) supertype" is a functional classification of HLA alleles, which was defined by structural features and peptide specificities, and has been reportedly associated with the clinical outcomes of viral infections and autoimmune diseases. Although the disparity in each HLA locus was reported to have no clinical significance in single-unit cord blood transplantation (sCBT), the clinical significance of the HLA supertype in sCBT remains unknown. Therefore, we retrospectively analyzed clinical data of 1603 patients who received sCBT in eight institutes in Japan between 2000 and 2017. Each HLA allele was categorized into 19 supertypes, and the prognostic effect of disparities was then assessed. An HLA-B supertype mismatch was identified as a poor prognostic factor (PFS: hazard ratio [HR] = 1.23, p = 0.00044) and was associated with a higher cumulative incidence (CI) of relapse (HR = 1.24, p = 0.013). However, an HLA-B supertype mismatch was not associated with the CI of acute and chronic graft-versus-host-disease. The multivariate analysis for relapse and PFS showed the significance of an HLA-B supertype mismatch independent of allelic mismatches, and other previously reported prognostic factors. HLA-B supertype-matched grafts should be selected in sCBT.
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http://dx.doi.org/10.1038/s41409-023-02183-1 | DOI Listing |
Bone Marrow Transplant
April 2024
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Gastric Cancer
January 2024
Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, South Korea.
Background: We conducted a trial to evaluate the efficacy and safety of nivolumab and paclitaxel as second-line therapy for immune-related biomarker-enriched advanced gastric cancer (AGC).
Methods: This open-label, single-arm, phase Ib/II study was a part of multi-institutional, biomarker-integrated umbrella study conducted in Korea. In phase Ib, patients received nivolumab (3 mg/kg) on Days 1 and 15 and paclitaxel (dose level 1, 70 mg/m or dose level 2, 80 mg/m) on Days 1, 8, 15 every four weeks.
Adv Med Sci
September 2023
Tissue Typing Centre, Clinical Department for Transfusion Medicine and Transplantation Biology, University Hospital Centre Zagreb, Zagreb, Croatia.
Purpose: This study retrospectively investigated the association between the level of human leukocyte antigen (HLA) mismatches (MMs), direction of disparities and differences at particular HLA locus on clinical outcomes of hematopoietic stem cell transplantation (HSCT). Investigated outcomes were overall survival (OS) and disease-free survival (DFS), graft-versus-host disease (GvHD), relapse and non-relapse mortality (NRM).
Patients And Methods: Study cohort included 108 adult patients transplanted between 2011 and 2021 and their 9/10 mismatched unrelated donors (MMUD).
Haematologica
October 2016
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
The diversity of the human leukocyte antigen (HLA) class I and II alleles can be simplified by consolidating them into fewer supertypes based on functional or predicted structural similarities in epitope-binding grooves of HLA molecules. We studied the impact of matched and mismatched HLA-A (265 versus 429), -B (230 versus 92), -C (365 versus 349), and -DRB1 (153 versus 51) supertypes on clinical outcomes of 1934 patients with acute leukemias or myelodysplasia/myeloproliferative disorders. All patients were reported to the Center for International Blood and Marrow Transplant Research following single-allele mismatched unrelated donor myeloablative conditioning hematopoietic cell transplantation.
View Article and Find Full Text PDFJ Exp Med
September 2003
Dept. of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria 3010, Australia.
HLA-B*4402 and B*4403 are naturally occurring MHC class I alleles that are both found at a high frequency in all human populations, and yet they only differ by one residue on the alpha2 helix (B*4402 Asp156-->B*4403 Leu156). CTLs discriminate between HLA-B*4402 and B*4403, and these allotypes stimulate strong mutual allogeneic responses reflecting their known barrier to hemopoeitic stem cell transplantation. Although HLA-B*4402 and B*4403 share >95% of their peptide repertoire, B*4403 presents more unique peptides than B*4402, consistent with the stronger T cell alloreactivity observed toward B*4403 compared with B*4402.
View Article and Find Full Text PDF