Multiple Mismatches at the Low Expression HLA Loci DP, DQ, and DRB3/4/5 Associate with Adverse Outcomes in Hematopoietic Stem Cell Transplantation

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2013 Apr 19

PMID 23596045

Citations 67

Authors

Marcelo A Fernandez-Vina

John P Klein

Michael Haagenson

Stephen R Spellman

Claudio Anasetti

Harriet Noreen

Lee Ann Baxter-Lowe

Pedro Cano

Neal Flomenberg

Dennis L Confer

Mary M Horowitz

Machteld Oudshoorn

Effie W Petersdorf

Michelle Setterholm

Richard Champlin

Stephanie J Lee

Marcos de Lima

Affiliations

Soon will be listed here.

Abstract

A single mismatch in highly expressed HLA-A, -B, -C, and -DRB1 loci (HEL) is associated with worse outcomes in hematopoietic stem cell transplantation, while less is known about the cumulative impact of mismatches in the lesser expressed HLA loci DRB3/4/5, DQ, and DP (LEL). We studied whether accumulation of LEL mismatches is associated with deleterious effects in 3853 unrelated donor transplants stratified according to number of matches in the HEL. In the 8/8 matched HEL group, LEL mismatches were not associated with any adverse outcome. Mismatches at HLA-DRB1 were associated with occurrence of multiple LEL mismatches. In the 7/8 HEL group, patients with 3 or more LEL mismatches scored in the graft-versus-host vector had a significantly higher risk of mortality (1.45 and 1.43) and transplant-related mortality (1.68 and 1.54) than the subgroups with 0 or 1 LEL mismatches. No single LEL locus had a more pronounced effect on clinical outcome. Three or more LEL mismatches are associated with lower survival after 7/8 HEL matched transplantation. Prospective evaluation of matching for HLA-DRB3/4/5, -DQ, and -DP loci is warranted to reduce posttransplant risks in donor-recipient pairs matched for 7/8 HEL.

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