Abstract:
BACKGROUND:Busulfan (Bu) and cyclophosphamide (Cy) are frequently included in conditioning regimens before hematopoietic stem cell transplantation (HSCT). Both drugs are detoxified by glutathione transferases (GST), and GST gene variants may explain some of the interindividual variability in pharmacokinetics and drug toxicity. METHODS:The study investigated adult patients (n = 114) receiving oral Bu pre-HSCT. Bu doses were adjusted to obtain an average steady-state concentration (Css) of 900 mcg/L. RESULTS:Median first dose Bu Css was 1000 mcg/L (600-1780 mcg/L). Patients carrying 1 and 2 GSTA1*B (rs3957357) alleles demonstrated median 12% and 16% higher Bu Css (P ≤ 0.05). Bu exposure (average Css; odds ratio = 1.009, 95% confidence interval = 1.002-1.017, P = 0.013) and GSTM1 gene copy number (odds ratio = 17.1, 95% confidence interval = 1.46-201, P = 0.024) were significant predictors of mortality ≤30 days. The mortality was 25% versus 2% among carriers of 2 versus no GSTM1 copies (P = 0.021). Mortality ≤3 months was associated with higher first dose Bu exposure (1090 versus 980 mcg/L, P = 0.021). GSTM1 expression and high Bu exposure may increase Cy toxicity by reducing intracellular glutathione. CONCLUSIONS:GST genotyping before HSCT may allow better prediction of Bu pharmacokinetics and drug toxicity, and thereby improve outcome after BuCy conditioning.
journal_name
Ther Drug Monitjournal_title
Therapeutic drug monitoringauthors
Bremer S,Fløisand Y,Brinch L,Gedde-Dahl T,Bergan Sdoi
10.1097/FTD.0000000000000180subject
Has Abstractpub_date
2015-08-01 00:00:00pages
493-500issue
4eissn
0163-4356issn
1536-3694journal_volume
37pub_type
杂志文章abstract::The prevalence of gestational ethanol exposure and subsequent fetal exposure has been assessed in a cohort of mother-infant dyads in a Mediterranean city (Barcelona, Spain) by meconium analysis of fatty acid ethyl esters (FAEEs) after showing in this population a high prevalence of meconium opiates (8.7%), cocaine (4....
journal_title:Therapeutic drug monitoring
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journal_title:Therapeutic drug monitoring
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journal_title:Therapeutic drug monitoring
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journal_title:Therapeutic drug monitoring
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journal_title:Therapeutic drug monitoring
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journal_title:Therapeutic drug monitoring
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journal_title:Therapeutic drug monitoring
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journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:
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journal_title:Therapeutic drug monitoring
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journal_title:Therapeutic drug monitoring
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journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章,多中心研究
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journal_title:Therapeutic drug monitoring
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journal_title:Therapeutic drug monitoring
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journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
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journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
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更新日期:1999-08-01 00:00:00
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journal_title:Therapeutic drug monitoring
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journal_title:Therapeutic drug monitoring
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journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
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更新日期:1992-10-01 00:00:00
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journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
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更新日期:2005-12-01 00:00:00
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journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,多中心研究
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