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MHC-resident variation affects risks after unrelated donor hematopoietic cell transplantation. Sci Transl Med 2012 Jul 25;4(144):144ra101 PMID: 22837536 PMCID: PMC3633562

Pubmed ID

22837536

Abstract

Blood malignancies can be cured with hematopoietic cell transplantation from human leukocyte antigen (HLA)-matched unrelated donors; however, acute graft-versus-host disease (GVHD) affects up to 80% of patients and contributes to increased mortality. To test the hypothesis that undetected patient-donor differences for non-HLA genetic variation within the major histocompatibility complex (MHC) could confer risks after HLA-matched transplantation, we conducted a discovery-validation study of 4205 transplants for 1120 MHC region single-nucleotide polymorphisms (SNPs). Two SNPs were identified as markers for disease-free survival and acute GVHD. Among patients with two or more HLA-matched unrelated donors identified on their search, SNP genotyping of patients and their potential donors demonstrated that most patients have a choice of SNP-matched donors. In conclusion, the success of HLA-matched unrelated donor hematopoietic cell transplantation depends on non-HLA MHC region genetic variation. Prospective SNP screening and matching provides an approach for lowering risks to patients.

Author List

Petersdorf EW, Malkki M, Gooley TA, Spellman SR, Haagenson MD, Horowitz MM, 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-s2.0-84864509466   39 Citations

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

Adolescent
Adult
Alleles
Child
Child, Preschool
Female
Genotype
Graft vs Host Disease
HLA-A Antigens
HLA-B Antigens
HLA-DQ beta-Chains
HLA-DRB1 Chains
Hematopoietic Stem Cell Transplantation
Humans
Infant
Infant, Newborn
Major Histocompatibility Complex
Male
Unrelated Donors
Young Adult
jenkins-FCD Prod-299 9ef562391eceb2b8f95265c767fbba1ce5a52fd6