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. 2015 Oct;21(10):1783-9.
doi: 10.1016/j.bbmt.2015.05.028. Epub 2015 Jun 6.

HLA Mismatch Is Associated with Worse Outcomes after Unrelated Donor Reduced-Intensity Conditioning Hematopoietic Cell Transplantation: An Analysis from the Center for International Blood and Marrow Transplant Research

Michael R Verneris  1 , Stephanie J Lee  2 , Kwang Woo Ahn  3 , Hai-Lin Wang  4 , Minoo Battiwalla  5 , Yoshihiro Inamoto  2 , Marcelo A Fernandez-Vina  6 , James Gajewski  7 , Joseph Pidala  8 , Reinhold Munker  9 , Mahmoud Aljurf  10 , Wael Saber  4 , Stephen Spellman  11 , John Koreth  12
Affiliations

HLA Mismatch Is Associated with Worse Outcomes after Unrelated Donor Reduced-Intensity Conditioning Hematopoietic Cell Transplantation: An Analysis from the Center for International Blood and Marrow Transplant Research

Michael R Verneris et al. Biol Blood Marrow Transplant. 2015 Oct.

Abstract

Over the past 2 decades, reduced-intensity conditioning allogeneic hematopoietic cell transplantation (RIC HCT) has increased substantially. Many patients do not have fully HLA-matched donors, and the impact of HLA mismatch on RIC HCT has not been examined in large cohorts. We analyzed 2588 recipients of 8/8 HLA-high resolution matched (n = 2025) or single-locus mismatched (n = 563) unrelated donor (URD) RIC HCT from 1999 to 2011. Overall survival (OS) was the primary outcome. Secondary endpoints included treatment-related mortality (TRM), relapse, disease-free survival (DFS), and acute/chronic graft-versus-host disease (GVHD). Adjusted 1- and 3-year OS was better in 8/8- versus 7/8-matched recipients (54.7% versus 48.8%, P = .01, and 37.4% versus 30.9%, P = .005, respectively). In multivariate models 7/8 URD RIC HCT recipients had more grades II to IV acute GVHD (RR = 1.29, P = .0034), higher TRM (RR = 1.52, P < .0001), and lower DFS (RR = 1.12, P = .0015) and OS (RR = 1.25, P = .0001), with no difference in relapse or chronic GVHD. In subgroup analysis, inferior transplant outcomes were noted regardless of the HLA allele mismatched. Previously reported permissive mismatches at HLA-C (C*03:03/C*03:04) and HLA-DP1 (based on T cell-epitope matching) were not associated with better outcomes. Although feasible, single-locus mismatch in RIC URD HCT is associated with inferior outcomes.

Keywords: Bone marrow transplantation; Hematologic malignancies; Leukemia; Pediatric oncology.

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Figures

Figure 1
Figure 1. Impact of Single Allele Mismatch on (A) aGVHD II-IV, (B) cumulative incidence of TRM and (C) OS
Figure 1
Figure 1. Impact of Single Allele Mismatch on (A) aGVHD II-IV, (B) cumulative incidence of TRM and (C) OS
See this image and copyright information in PMC

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