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Mapping MHC haplotype effects in unrelated donor hematopoietic cell transplantation. Blood 2013 Mar 07;121(10):1896-905 PMID: 23305741 PMCID: PMC3591807

Pubmed ID

23305741

DOI

10.1182/blood-2012-11-465161

Abstract

Life-threatening risks associated with HLA-mismatched unrelated donor hematopoietic cell transplantation limit its general application for the treatment of blood diseases. The increased risks might be explained by undetected genetic variation within the highly polymorphic major histocompatibility complex (MHC) region. We retrospectively assessed each of 1108 MHC region single nucleotide polymorphisms (SNPs) in 2628 patients and their HLA-mismatched unrelated donors to determine whether SNPs are associated with the risk of mortality, disease-free survival, transplant-related mortality, relapse, and acute and chronic graft-versus-host disease (GVHD). Multivariate analysis adjusted for HLA mismatching and nongenetic variables associated with each clinical end point. Twelve SNPs were identified as transplantation determinants. SNP-associated risks were conferred by either patient or donor SNP genotype or by patient-donor SNP mismatching. Risks after transplantation increased with increasing numbers of unfavorable SNPs. SNPs that influenced acute GVHD were independent of those that affected risk of chronic GVHD and relapse. HLA haplotypes differed with respect to haplotype content of (un)favorable SNPs. Outcome after HLA-mismatched unrelated donor transplantation is influenced by MHC region variation that is undetected with conventional HLA typing. Knowledge of the SNP content of HLA haplotypes provides a means to estimate risks prior to transplantation and to lower complications through judicious selection of donors with favorable MHC genetics.

Author List

Petersdorf EW, Malkki M, Horowitz MM, Spellman SR, Haagenson MD, Wang T

Authors

Mary M. Horowitz MD, MS 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




Scopus

2-s2.0-84876589420   33 Citations

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

Acute Disease
Adolescent
Adult
Biomarkers, Tumor
Child
Child, Preschool
Chronic Disease
DNA, Neoplasm
Female
Genotype
Graft vs Host Disease
Haplotypes
Hematologic Neoplasms
Hematopoietic Stem Cell Transplantation
Histocompatibility Testing
Humans
Infant
Infant, Newborn
Major Histocompatibility Complex
Male
Neoplasm Recurrence, Local
Polymerase Chain Reaction
Polymorphism, Single Nucleotide
Prognosis
Retrospective Studies
Survival Rate
Transplantation, Homologous
Unrelated Donors
Young Adult
jenkins-FCD Prod-331 a335b1a6d1e9c32173c9534e6f6ff51494143916