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, Stephanie J. Lee, Kwang Woo Ahn, Hai Lin Wang, Minoo Battiwalla, Yoshihiro Inamoto, Marcelo A. Fernandez-Vina, James Gajewski, Joseph Pidala, Reinhold Munker, Mahmoud Aljurf, Wael Saber, Stephen Spellman, John Koreth

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1783-1789
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume21
Issue number10
DOIs
StatePublished - Oct 1 2015

Bibliographical note

Publisher Copyright:
© 2015 American Society for Blood and Marrow Transplantation.

Keywords

  • Bone marrow transplantation
  • Hematologic malignancies
  • Leukemia
  • Pediatric oncology

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