Pretreatment plasma folate modulates the pharmacodynamic effect of high-dose methotrexate in children with acute lymphoblastic leukemia and non-Hodgkin lymphoma: "folate overrescue" concept revisited
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
16455868
DOI
10.1373/clinchem.2005.061150
PII: clinchem.2005.061150
Knihovny.cz E-resources
- MeSH
- Precursor Cell Lymphoblastic Leukemia-Lymphoma blood drug therapy MeSH
- Child MeSH
- Homocysteine blood MeSH
- Infant MeSH
- Folic Acid blood MeSH
- Leucovorin therapeutic use MeSH
- Humans MeSH
- Methotrexate administration & dosage adverse effects therapeutic use MeSH
- Adolescent MeSH
- Lymphoma, Non-Hodgkin blood drug therapy MeSH
- Child, Preschool MeSH
- Antimetabolites, Antineoplastic administration & dosage adverse effects therapeutic use MeSH
- Vitamin B 12 blood MeSH
- Vitamin B Complex therapeutic use MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Homocysteine MeSH
- Folic Acid MeSH
- Leucovorin MeSH
- Methotrexate MeSH
- Antimetabolites, Antineoplastic MeSH
- Vitamin B 12 MeSH
- Vitamin B Complex MeSH
BACKGROUND: To evaluate the influence of pretreatment plasma folate concentrations on methotrexate exposure in children with acute lymphoblastic leukemia/non-Hodgkin lymphoma treated with high-dose methotrexate, we assessed time profiles of plasma homocysteine, folate, and vitamin B(12) concentrations in children treated with high-dose methotrexate with leucovorin rescue. METHODS: We analyzed 98 treatment courses. The study endpoints were to determine how methotrexate exposure is related to homocysteine accumulation and whether it is influenced by pretreatment plasma folate. RESULTS: Peak concentrations of homocysteine increased from the start of the intravenous infusion through cessation of methotrexate therapy up to time point t(42), when this trend was reversed by administration of folinic acid. The area under the curve (AUC) for plasma homocysteine showed decreasing course-to-course tendencies with a statistically significant decrease only between courses 1 and 2 (P
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