PMID- 20335219
OWN - NLM
STAT- MEDLINE
DCOM- 20100719
LR  - 20221207
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 115
IP  - 23
DP  - 2010 Jun 10
TI  - Impact of highly conserved HLA haplotype on acute graft-versus-host disease.
PG  - 4664-70
LID - 10.1182/blood-2009-10-251157 [doi]
AB  - Although the effects of human leukocyte antigen (HLA) locus matching on clinical 
      outcome in unrelated hematopoietic stem cell transplantations have been 
      characterized, the biologic implications of HLA haplotypes have not been defined. 
      We demonstrated the genetic fixity of Japanese conserved extended haplotypes by 
      multi-single nucleotide polymorphism analysis in 1810 Japanese donor-recipient 
      pairs matching with HLA-A, -B, -C, -DRB1, and -DQB1 alleles. Three major Japanese 
      conserved extended haplotypes (named HP-P1, HP-P2, and HP-P3) were essentially 
      completely conserved at least in the 3.3-Mb HLA region from HLA-A to -DPB1, and 
      extended far beyond HLA-A. The risk of acute graft-versus-host disease (GVHD) of 
      these HLA haplotypes was assessed with multivariate Cox regression in 712 
      patients transplanted from HLA fully (HLA-A, B, C, DRB1, DQB1, and DPB1) matched 
      unrelated donors. HP-P2 itself reduced the risk of grade 2 to 4 acute GVHD 
      (hazard ratio [HR] = 0.63; P = .032 compared with HP-P2-negative), whereas HP-P3 
      tended to increase the risk (HR = 1.38; P = .07). Among 381 patients with HP-P1, 
      HP-P1/P3 (HR = 3.35; P = .024) significantly increased the risk of acute GVHD 
      compared with homozygous HP-P1. This study is the first to demonstrate that a 
      genetic difference derived from HLA haplotype itself is associated with acute 
      GVHD in allogeneic hematopoietic stem cell transplantation.
FAU - Morishima, Satoko
AU  - Morishima S
AD  - Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, 
      Japan.
FAU - Ogawa, Seishi
AU  - Ogawa S
FAU - Matsubara, Aiko
AU  - Matsubara A
FAU - Kawase, Takakazu
AU  - Kawase T
FAU - Nannya, Yasuhito
AU  - Nannya Y
FAU - Kashiwase, Koichi
AU  - Kashiwase K
FAU - Satake, Masahiro
AU  - Satake M
FAU - Saji, Hiroo
AU  - Saji H
FAU - Inoko, Hidetoshi
AU  - Inoko H
FAU - Kato, Shunichi
AU  - Kato S
FAU - Kodera, Yoshihisa
AU  - Kodera Y
FAU - Sasazuki, Takehiko
AU  - Sasazuki T
FAU - Morishima, Yasuo
AU  - Morishima Y
CN  - Japan Marrow Donor Program
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100324
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Histocompatibility Antigens Class I)
SB  - IM
MH  - Acute Disease
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Asian People
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - *Genetic Loci
MH  - Genome-Wide Association Study
MH  - Graft vs Host Disease/*genetics/prevention & control
MH  - *Haplotypes
MH  - Hematologic Neoplasms/genetics/therapy
MH  - Hematopoietic Stem Cell Transplantation
MH  - Histocompatibility Antigens Class I/*genetics
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Japan
MH  - Male
MH  - Middle Aged
MH  - *Polymorphism, Single Nucleotide
MH  - Retrospective Studies
MH  - Risk Factors
MH  - Transplantation, Homologous
EDAT- 2010/03/26 06:00
MHDA- 2010/07/20 06:00
CRDT- 2010/03/26 06:00
PHST- 2010/03/26 06:00 [entrez]
PHST- 2010/03/26 06:00 [pubmed]
PHST- 2010/07/20 06:00 [medline]
AID - S0006-4971(20)34884-9 [pii]
AID - 10.1182/blood-2009-10-251157 [doi]
PST - ppublish
SO  - Blood. 2010 Jun 10;115(23):4664-70. doi: 10.1182/blood-2009-10-251157. Epub 2010 
      Mar 24.