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Sci Transl Med. 2012 Jul 25;4(144):144ra101. doi: 10.1126/scitranslmed.3003974.

MHC-resident variation affects risks after unrelated donor hematopoietic cell transplantation.

Author information

  • 1Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. epetersd@fhcrc.org

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.

PMID:
22837536
[PubMed - indexed for MEDLINE]
PMCID:
PMC3633562
Free PMC Article

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