PMID- 23813863
OWN - NLM
STAT- MEDLINE
DCOM- 20131209
LR  - 20130930
IS  - 1096-8652 (Electronic)
IS  - 0361-8609 (Linking)
VI  - 88
IP  - 10
DP  - 2013 Oct
TI  - A polymorphism in the TYMP gene is associated with the outcome of HLA-identical 
      sibling allogeneic stem cell transplantation.
PG  - 883-9
LID - 10.1002/ajh.23523 [doi]
AB  - Thymidine phosphorylase (TYMP), an enzyme involved in nucleotide synthesis, has 
      been implicated in critical biological processes such as DNA replication, 
      protection against mutations, and tissue repair. In this work, we retrospectively 
      evaluated the influence of a polymorphism in the TYMP gene (rs112723255; G/A) 
      upon the outcome of 448 patients subjected to allogeneic stem cell 
      transplantation (allo-SCT) from an human leukocyte antigen (HLA)-identical 
      sibling donor. The TYMP genotype of patients correlated with overall 
      survival-carriers of the minor allele (A) being at an increased risk of dying 
      after transplantation (hazard ratio, HR = 1.9; P = 0.004). This effect was mostly 
      due to differences in transplant toxicity-related mortality (HR = 2.5; P = 
      0.029). In addition, the TYMP genotype of donors was associated with the risk of 
      chronic graft-versus-host disease (GVHD)-carriers of the minor allele being at an 
      increased risk of developing this complication ([HR] = 1.7; P = 0.039). The 
      impact of such polymorphism on the risk of chronic GVHD is limited to patients 
      transplanted in early stage disease (HR = 2.2; P = 0.019). The combination of a 
      donor harboring the minor allele with a patient homozygous for the major allele 
      was associated with the highest risk of chronic GVHD (HR = 2.8; P = 0.008). These 
      findings provide the first evidence of the significant impact of the TYMP 
      genotype upon the clinical outcome of patients treated with HLA-identical sibling 
      allo-SCT.
CI  - (c) 2013 Wiley Periodicals, Inc.
FAU - Guillem, Vicent
AU  - Guillem V
AD  - Department of Hematology and Medical Oncology, Hospital Clinico Universitario de 
      Valencia, Instituto de Investigacion Sanitaria INCLIVA, Universitat de Valencia, 
      Valencia, Spain.
FAU - Hernandez-Boluda, Juan Carlos
AU  - Hernandez-Boluda JC
FAU - Gallardo, David
AU  - Gallardo D
FAU - Buno, Ismael
AU  - Buno I
FAU - Bosch, Anna
AU  - Bosch A
FAU - Martinez-Laperche, Carolina
AU  - Martinez-Laperche C
FAU - de la Camara, Rafael
AU  - de la Camara R
FAU - Brunet, Salut
AU  - Brunet S
FAU - Martin, Carmen
AU  - Martin C
FAU - Nieto, Jose B
AU  - Nieto JB
FAU - Martinez, Carmen
AU  - Martinez C
FAU - Perez, Ariadna
AU  - Perez A
FAU - Montoro, Juan
AU  - Montoro J
FAU - Garcia-Noblejas, Ana
AU  - Garcia-Noblejas A
FAU - Solano, Carlos
AU  - Solano C
CN  - Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group (GETH)
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20130801
PL  - United States
TA  - Am J Hematol
JT  - American journal of hematology
JID - 7610369
RN  - EC 2.4.2.4 (TYMP protein, human)
RN  - EC 2.4.2.4 (Thymidine Phosphorylase)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Alleles
MH  - Child
MH  - Child, Preschool
MH  - Chronic Disease
MH  - Female
MH  - *Genotype
MH  - *Graft vs Host Disease/etiology/genetics/mortality
MH  - *Hematologic Neoplasms/genetics/mortality/therapy
MH  - Histocompatibility Testing
MH  - Humans
MH  - Infant
MH  - Male
MH  - Middle Aged
MH  - *Polymorphism, Genetic
MH  - Retrospective Studies
MH  - Risk Factors
MH  - *Siblings
MH  - *Stem Cell Transplantation
MH  - Survival Rate
MH  - Thymidine Phosphorylase/*genetics
MH  - Time Factors
MH  - Transplantation, Homologous
EDAT- 2013/07/03 06:00
MHDA- 2013/12/16 06:00
CRDT- 2013/07/02 06:00
PHST- 2013/05/09 00:00 [received]
PHST- 2013/06/19 00:00 [revised]
PHST- 2013/06/20 00:00 [accepted]
PHST- 2013/07/02 06:00 [entrez]
PHST- 2013/07/03 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
AID - 10.1002/ajh.23523 [doi]
PST - ppublish
SO  - Am J Hematol. 2013 Oct;88(10):883-9. doi: 10.1002/ajh.23523. Epub 2013 Aug 1.