| Therapeutic drug monitoring of methotrexate in cerebrospinal fluid after systemic high-dose infusion in children: can the burden of intrathecal methotrexate be reduced? | |
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MedLine Citation:
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PMID: 20571463 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The use of intrathecal (IT) methotrexate (MTX) in combination with systemic high-dose (HD) MTX is an established procedure for central nervous system prophylaxis in patients with acute lymphoblastic leukemia, but the evidence for the necessity of this combination is not convincing. The MTX concentration in the cerebrospinal fluid (CSF) was evaluated in 138 samples from children with acute lymphoblastic leukemia and non-Hodgkin lymphoma. CSF samples were obtained by lumbar puncture 12-24 hours after starting the HD MTX infusion (5 g/m2 over 24 hours) and immediately before the IT administration of MTX. Serum MTX concentrations at the end of infusion were assessed by routine therapeutic drug monitoring. Cytotoxic MTX concentrations of 1 microM or greater were detected in 81.2% of CSF samples. CSF MTX concentrations were significantly lower in samples from patients younger than 7 years. The correlation between MTX concentrations in the serum and the CSF was moderate (r = 0.451) and became stronger with increasing age. The median CSF MTX concentrations per cycle were comparable (1.40, 1.25, 1.39, 1.38 microM for cycles 1-4, respectively). The predictive value and the accuracy of the CSF MTX concentration measured during the first cycle of HD MTX in respect to concentrations in the following cycles were high (94.4% and 85.7%, respectively) suggesting that the CSF MTX concentration during the first HD MTX infusion is a useful predictor for sufficient CSF MTX concentrations in the following HD MTX cycles. Our results confirm previously published data on MTX accumulation in the CSF after 5 g/m2 MTX over 24 hours in an independent cohort monitored in a real-life setting. Based on the common opinion that 1 microM represents the minimal antileukemic MTX concentration, current data warrant reevaluation of the necessity of routine IT MTX following HD MTX. Our findings offer a perspective on reducing the burden of IT MTX in children on consolidation therapy by CSF MTX drug monitoring. |
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Authors:
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Andreas Niemann; Jörg Mühlisch; Michael C Frühwald; Joachim Gerss; Georg Hempel; Joachim Boos |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Therapeutic drug monitoring Volume: 32 ISSN: 1536-3694 ISO Abbreviation: Ther Drug Monit Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-28 Completed Date: 2010-11-05 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7909660 Medline TA: Ther Drug Monit Country: United States |
Other Details:
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Languages: eng Pagination: 467-75 Citation Subset: IM |
Affiliation:
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Department of Pediatric Hematology and Oncology, University Children's Hospital, Münster, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Aging / metabolism Antimetabolites, Antineoplastic / administration & dosage, cerebrospinal fluid* Biotransformation Child Child, Preschool Drug Monitoring Humans Infant Infusions, Intravenous Injections, Spinal Leukemia / blood, drug therapy Mass Spectrometry Methotrexate / administration & dosage, cerebrospinal fluid* Neoplasms / cerebrospinal fluid, drug therapy Retrospective Studies Risk Assessment Young Adult |
| Chemical | |
Reg. No./Substance:
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0/Antimetabolites, Antineoplastic; 59-05-2/Methotrexate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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