Faculty Collaboration Database

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. Biol Blood Marrow Transplant 2015 Oct;21(10):1783-9

Date

06/10/2015

Pubmed ID

26055300

Pubmed Central ID

PMC4568127

DOI

10.1016/j.bbmt.2015.05.028

Scopus ID

2-s2.0-84941318174 (requires institutional sign-in at Scopus site)   81 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.

Author List

Verneris MR, Lee SJ, Ahn KW, Wang HL, Battiwalla M, Inamoto Y, Fernandez-Vina MA, Gajewski J, Pidala J, Munker R, Aljurf M, Saber W, Spellman S, Koreth J

Authors

Kwang Woo Ahn PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Wael Saber MD, MS Professor in the Medicine department at Medical College of Wisconsin

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

Adolescent
Adult
Aged
Disease-Free Survival
Female
Graft vs Host Disease
HLA Antigens
Hematopoietic Stem Cell Transplantation
Histocompatibility
Histocompatibility Testing
Humans
Kaplan-Meier Estimate
Leukemia
Living Donors
Male
Middle Aged
Myelodysplastic Syndromes
Proportional Hazards Models
Registries
Retrospective Studies
Transplantation Conditioning
Treatment Outcome
Young Adult