MHC-resident variation affects risks after unrelated donor hematopoietic cell transplantation. Sci Transl Med 2012 Jul 25;4(144):144ra101
Date
07/28/2012Pubmed ID
22837536Pubmed Central ID
PMC3633562DOI
10.1126/scitranslmed.3003974Scopus ID
2-s2.0-84864509466 (requires institutional sign-in at Scopus site) 50 CitationsAbstract
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 TAuthors
Mary M. Horowitz MD, MS Professor in the Medicine department at Medical College of WisconsinTao 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
AdolescentAdult
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
