PMID- 22837536
OWN - NLM
STAT- MEDLINE
DCOM- 20121204
LR  - 20211021
IS  - 1946-6242 (Electronic)
IS  - 1946-6234 (Print)
IS  - 1946-6234 (Linking)
VI  - 4
IP  - 144
DP  - 2012 Jul 25
TI  - MHC-resident variation affects risks after unrelated donor hematopoietic cell 
      transplantation.
PG  - 144ra101
LID - 10.1126/scitranslmed.3003974 [doi]
AB  - 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.
FAU - Petersdorf, Effie W
AU  - Petersdorf EW
AD  - Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, 
      WA 98109, USA. epetersd@fhcrc.org
FAU - Malkki, Mari
AU  - Malkki M
FAU - Gooley, Theodore A
AU  - Gooley TA
FAU - Spellman, Stephen R
AU  - Spellman SR
FAU - Haagenson, Michael D
AU  - Haagenson MD
FAU - Horowitz, Mary M
AU  - Horowitz MM
FAU - Wang, Tao
AU  - Wang T
LA  - eng
GR  - CA18029/CA/NCI NIH HHS/United States
GR  - P01 CA018029/CA/NCI NIH HHS/United States
GR  - U24 CA076518/CA/NCI NIH HHS/United States
GR  - U01 AI069197/AI/NIAID NIH HHS/United States
GR  - HHSH234200637015C/PHS HHS/United States
GR  - CA76518/CA/NCI NIH HHS/United States
GR  - R01 CA100019/CA/NCI NIH HHS/United States
GR  - AI069197/AI/NIAID NIH HHS/United States
GR  - CA100019/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Sci Transl Med
JT  - Science translational medicine
JID - 101505086
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQB1 antigen)
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Alleles
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - Genotype
MH  - Graft vs Host Disease/genetics
MH  - HLA-A Antigens/genetics
MH  - HLA-B Antigens/genetics
MH  - HLA-DQ beta-Chains/genetics
MH  - HLA-DRB1 Chains/genetics
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Major Histocompatibility Complex/*genetics
MH  - Male
MH  - Unrelated Donors
MH  - Young Adult
PMC - PMC3633562
MID - NIHMS453123
COIS- Competing interests: The authors have no competing interests.
EDAT- 2012/07/28 06:00
MHDA- 2012/12/10 06:00
PMCR- 2013/04/23
CRDT- 2012/07/28 06:00
PHST- 2012/07/28 06:00 [entrez]
PHST- 2012/07/28 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
PHST- 2013/04/23 00:00 [pmc-release]
AID - 4/144/144ra101 [pii]
AID - 10.1126/scitranslmed.3003974 [doi]
PST - ppublish
SO  - Sci Transl Med. 2012 Jul 25;4(144):144ra101. doi: 10.1126/scitranslmed.3003974.