PMID- 11698304
OWN - NLM
STAT- MEDLINE
DCOM- 20011221
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 98
IP  - 10
DP  - 2001 Nov 15
TI  - Bone marrow transplantation from unrelated donors: the impact of mismatches with 
      substitutions at position 116 of the human leukocyte antigen class I heavy chain.
PG  - 3150-5
AB  - The hypothesis was tested that amino acid substitutions in specific positions 
      within human leukocyte antigen class I heavy chain would have different impacts 
      on transplant-related mortality (TRM) in patients receiving transplanted bone 
      marrow from unrelated donors. One hundred patients and their unrelated donors 
      were typed by sequence-based typing for the human leukocyte antigen (HLA)-A, -B, 
      and -C loci. All pairs were matched for DRB1, DRB3, DRB4, DRB5, DQA1, and DQB1 
      loci. Forty pairs were also matched at class I, and 60 pairs had one or more 
      mismatches at class I loci. It was found that substitutions at positions 116 and 
      114 of class I heavy chain significantly increased the risk for TRM in univariate 
      and bivariate Cox analyses. Conversely, no association between number of multiple 
      mismatches or number of amino acid substitutions and TRM was seen when positions 
      116 and 114 were adjusted for. Variables predictive of TRM in multivariate Cox 
      analysis were number of cells infused, diagnosis (chronic myeloid leukemia [CML] 
      or non-CML), and amino acid substitution at position 116 or 152. The only 
      variable predictive of severe acute graft-versus-host disease (GVHD) in 
      multivariate Cox analysis was substitution at position 116. Actuarial risk for 
      acute GVHD grade III-IV, TRM, and relapse in pairs with substitutions at position 
      116 (n = 37) compared to other pairs (n = 63) was, respectively, 36% versus 14% 
      (P =.01), 59% versus 28% (P =.001), and 25% versus 31% (P =.4). In conclusion 
      these data suggest that substitutions at position 116 of class I heavy chain 
      increase the risk for acute GVHD and TRM in patients who receive transplanted 
      bone marrow from unrelated donors.
FAU - Ferrara, G B
AU  - Ferrara GB
AD  - Laboratorio di Immunogenetica, Servizio di Epidemiologia Clinica, Istituto 
      Nazionale per la Ricerca sul Cancro, Genoa, Italy. ferrara@cba.unige.it
FAU - Bacigalupo, A
AU  - Bacigalupo A
FAU - Lamparelli, T
AU  - Lamparelli T
FAU - Lanino, E
AU  - Lanino E
FAU - Delfino, L
AU  - Delfino L
FAU - Morabito, A
AU  - Morabito A
FAU - Parodi, A M
AU  - Parodi AM
FAU - Pera, C
AU  - Pera C
FAU - Pozzi, S
AU  - Pozzi S
FAU - Sormani, M P
AU  - Sormani MP
FAU - Bruzzi, P
AU  - Bruzzi P
FAU - Bordo, D
AU  - Bordo D
FAU - Bolognesi, M
AU  - Bolognesi M
FAU - Bandini, G
AU  - Bandini G
FAU - Bontadini, A
AU  - Bontadini A
FAU - Barbanti, M
AU  - Barbanti M
FAU - Frumento, G
AU  - Frumento G
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Codon)
SB  - IM
MH  - Adult
MH  - Alleles
MH  - *Amino Acid Substitution
MH  - *Bone Marrow Transplantation/mortality
MH  - Codon/*genetics
MH  - Disease-Free Survival
MH  - Exons/genetics
MH  - Gene Frequency
MH  - *Genes, MHC Class I
MH  - Graft vs Host Disease/etiology/genetics/mortality
MH  - *Histocompatibility
MH  - Histocompatibility Testing
MH  - Humans
MH  - Life Tables
MH  - Polymorphism, Genetic
MH  - Proportional Hazards Models
MH  - Retrospective Studies
MH  - Risk Factors
MH  - Survival Analysis
MH  - Tissue Donors
MH  - *Transplantation, Homologous/mortality
MH  - Treatment Outcome
EDAT- 2001/11/08 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/11/08 10:00
PHST- 2001/11/08 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/11/08 10:00 [entrez]
AID - S0006-4971(20)56854-7 [pii]
AID - 10.1182/blood.v98.10.3150 [doi]
PST - ppublish
SO  - Blood. 2001 Nov 15;98(10):3150-5. doi: 10.1182/blood.v98.10.3150.