Faculty Collaboration Database

Impact of Previously Unrecognized HLA Mismatches Using Ultrahigh Resolution Typing in Unrelated Donor Hematopoietic Cell Transplantation. J Clin Oncol 2021 Jul 20;39(21):2397-2409

Date

04/10/2021

Pubmed ID

33835855

Pubmed Central ID

PMC8280068

DOI

10.1200/JCO.20.03643

Scopus ID

2-s2.0-85112125420 (requires institutional sign-in at Scopus site)   19 Citations

Abstract

PURPOSE: Ultrahigh resolution (UHR) HLA matching is reported to result in better outcomes following unrelated donor hematopoietic cell transplantation, improving survival and reducing post-transplant complications. However, most studies included relatively small numbers of patients. Here we report the findings from a large, multicenter validation study.

METHODS: UHR HLA typing was available on 5,140 conventionally 10 out of 10 HLA-matched patients with malignant disease transplanted between 2008 and 2017.

RESULTS: After UHR HLA typing, 82% of pairs remained 10 out of 10 UHR-matched; 12.3% of patients were 12 out of 12 UHR HLA-matched. Compared with 12 out of 12 UHR-matched patients, probabilities of grade 2-4 acute graft-versus-host disease (aGVHD) were significantly increased with UHR mismatches (overall P = .0019) and in those patients who were HLA-DPB1 T-cell epitope permissively mismatched or nonpermissively mismatched (overall P = .0011). In the T-cell-depleted subset, the degree of UHR HLA mismatch was only associated with increased transplant-related mortality (TRM) (overall P = .0068). In the T-cell-replete subset, UHR HLA matching was associated with a lower probability of aGVHD (overall P = .0020); 12 out of 12 UHR matching was associated with reduced TRM risk when compared with HLA-DPB1 T-cell epitope permissively mismatched patients, whereas nonpermissive mismatching resulted in a greater risk (overall P = .0003).

CONCLUSION: This study did not confirm that UHR 12 out of 12 HLA matching increases the probability of overall survival but does demonstrate that aGVHD risk, and in certain settings TRM, is lowest in UHR HLA-matched pairs and thus warrants consideration when multiple 10 out of 10 HLA-matched donors of equivalent age are available.

Author List

Mayor NP, Wang T, Lee SJ, Kuxhausen M, Vierra-Green C, Barker DJ, Auletta J, Bhatt VR, Gadalla SM, Gragert L, Inamoto Y, Morris GP, Paczesny S, Reshef R, Ringdén O, Shaw BE, Shaw P, Spellman SR, Marsh SGE

Authors

Bronwen E. Shaw MBChB, PhD Center Director, Professor in the Medicine department at Medical College of Wisconsin
Tao Wang PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin

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

Adolescent
Adult
Child
Child, Preschool
Female
Hematopoietic Stem Cell Transplantation
Histocompatibility Testing
Humans
Infant
Infant, Newborn
Male
Transplantation Conditioning
Unrelated Donors
Young Adult