Abstract:
:Allo-SCT using unrelated donors is a curative treatment for patients with hematological disorders. The best donor is one matched for 10/10 HLA alleles, however studies have shown an additional survival benefit when considering other genetic factors. It has been shown that a six-nucleotide insertion/deletion polymorphism in the CASP8 gene promoter results in reduced susceptibility of T lymphocytes to undergo apoptosis. In 186 SCT recipients, we found a significantly better OS in those who received a transplant from a WT/WT donor compared with donors with a deletion (3 years: 52 vs 34%; P=0.03; multivariate analysis; RR 0.61; 95% CI 0.38-0.98, P=0.04). This was more marked when both the patient and the donor had a deletion (3 years OS: 62% compared with 36%, P=0.01). As the majority of these patients received Alemtuzumab during conditioning, we went on to analyze the in vitro effect of the polymorphism on Alemtuzumab-induced apoptosis. We showed statistically significantly higher percentages of apoptotic naïve CD4 (P<0.0005) and CD8 (P<0.0005) T cells in WT/WT donors in comparison with donors with a deletion. These data imply an unrecognized role for the CASP8 promoter polymorphism on survival following unrelated SCT particularly in the context of T-cell depletion with Alemtuzumab.
journal_name
Bone Marrow Transplantjournal_title
Bone marrow transplantationauthors
Shaw BE,Lee F,Krishnamurthy S,Byrne JL,Seedhouse C,Mayor NP,Maldonado-Torres H,Saudemont A,Marsh SG,Madrigal JA,Russell NHdoi
10.1038/bmt.2014.238subject
Has Abstractpub_date
2015-02-01 00:00:00pages
237-43issue
2eissn
0268-3369issn
1476-5365pii
bmt2014238journal_volume
50pub_type
临床试验,杂志文章,多中心研究abstract::We report the results of a retrospective analysis in 27 pediatric patients who received low-dose MTX as the second-line treatment for steroid-refractory or -dependent acute and chronic GVHD. Between July 2000 and May 2006, 10 patients with aGVHD and 17 with cGVHD were treated with MTX at a dose of 3-10 mg/m(2) weekly....
journal_title:Bone marrow transplantation
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journal_title:Bone marrow transplantation
pub_type: 杂志文章
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journal_title:Bone marrow transplantation
pub_type: 杂志文章
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pub_type: 杂志文章,多中心研究
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journal_title:Bone marrow transplantation
pub_type: 杂志文章
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journal_title:Bone marrow transplantation
pub_type: 杂志文章
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pub_type: 杂志文章,多中心研究,随机对照试验
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journal_title:Bone marrow transplantation
pub_type: 杂志文章,评审
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journal_title:Bone marrow transplantation
pub_type: 临床试验,杂志文章,评审
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