Abstract | BACKGROUND: Recently, several important polymorphisms have been identified in T-cell activation and effector pathway genes and have been reported to be associated with inter-patient variability in alloimmune responses. The present study was designed to assess the impact of these genetic variations on the outcomes of allogeneic hematopoietic stem cell transplantation. DESIGN AND METHODS: We first investigated ten single nucleotide polymorphisms in six genes, CD28, inducible co-stimulator, cytotoxic T-lymphocyte antigen 4, granzyme B, Fas and Fas ligand, in 138 pairs of patients and their unrelated donors and a second cohort of 102 pairs of patients and their HLA-identical sibling donors. RESULTS: We observed that patients receiving stem cells from a donor with the cytotoxic T-lymphocyte antigen 4 gene CT60 variant allele (AA genotype) had a reduced incidence of grades II-IV acute graft-versus-host disease; however, they experienced early cytomegalovirus infection and relapsed more frequently, which suggested an interaction between the donor cytotoxic T-lymphocyte antigen 4 gene CT60 AA genotype and reduced T-cell alloreactivity. Furthermore, an unrelated donor with the granzyme B +55 variant genotype (AA) was an independent risk factor for development of grades II-IV acute graft-versus-host disease (P=0.024, RR=1.811). Among patients with acute myelogenous leukemia, those with the Fas -670 TT genotype were at higher risk of relapse (P=0.003, RR=3.823). The presence of these susceptible alleles in the donor and/or patient resulted in worse overall survival (54.9% versus 69.5%, P=0.029). CONCLUSIONS:
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Authors | Haowen Xiao, Yi Luo, Xiaoyu Lai, Shan Fu, Jimin Shi, Yamin Tan, Jingsong He, Wanzhuo Xie, Weiyan Zheng, Li-Mengmeng Wang, Lifei Zhang, Lizhen Liu, Xiujin Ye, Xiaohong Yu, Zhen Cai, Maofang Lin, He Huang |
Journal | Haematologica
(Haematologica)
Vol. 97
Issue 12
Pg. 1804-12
(Dec 2012)
ISSN: 1592-8721 [Electronic] Italy |
PMID | 22733023
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- CD28 Antigens
- CTLA-4 Antigen
- FAS protein, human
- Fas Ligand Protein
- ICOS protein, human
- Inducible T-Cell Co-Stimulator Protein
- fas Receptor
- Granzymes
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Topics |
- Adolescent
- Adult
- CD28 Antigens
(genetics)
- CTLA-4 Antigen
(genetics)
- Child
- Cohort Studies
- Fas Ligand Protein
(genetics)
- Female
- Follow-Up Studies
- Graft vs Host Disease
- Granzymes
(genetics)
- Hematologic Neoplasms
(etiology, mortality, therapy)
- Hematopoietic Stem Cell Transplantation
- Humans
- Immunity, Cellular
- Inducible T-Cell Co-Stimulator Protein
(genetics)
- Lymphocyte Activation
- Male
- Middle Aged
- Neoplasm Recurrence, Local
(etiology, mortality, therapy)
- Polymerase Chain Reaction
- Polymorphism, Single Nucleotide
(genetics)
- Prognosis
- Risk Assessment
- Siblings
- Survival Rate
- T-Lymphocytes
(immunology)
- Tissue Donors
- Transplantation, Homologous
- Young Adult
- fas Receptor
(genetics)
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