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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
|
| pubmed:dateCreated |
1986-3-10
|
| pubmed:abstractText |
High-dose methotrexate (500 to 33,600 mg per square meter of body-surface area) with leucovorin rescue is a common component of therapy for acute lymphocytic leukemia. To increase understanding of the relation between the serum concentration and the effect of methotrexate, we conducted a randomized, prospective study of 108 children with "standard-risk" acute lymphocytic leukemia who were treated with 15 doses of methotrexate (1000 mg per square meter) that were infused over 24 hours. The median length of follow-up was 3.5 years from diagnosis for patients still in remission. Variability between patients in methotrexate clearance produced steady-state serum concentrations that ranged from 9.3 to 25.4 microM. Patients with median methotrexate concentrations of less than 16 microM (n = 59) had a lower probability of remaining in remission (P less than 0.05) than patients with concentrations of 16 microM or more (n = 49). Multivariate analyses indicated that patients with methotrexate concentrations of less than 16 microM were 3 times more likely to have any kind of relapse during therapy (P = 0.01) and 7 times more likely to have a hematologic relapse during therapy (P = 0.001). Stepwise Cox's regression identified leukemic-cell DNA content, methotrexate concentration, and hemoglobin as significant prognostic variables for hematologic relapse (P = 0.0005). We conclude that there is a concentration-effect relation for high-dose methotrexate in acute lymphocytic leukemia and that 1000 mg per square meter infused over a period of 24 hours may not be optimal for patients with relatively fast drug clearance.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Feb
|
| pubmed:issn |
0028-4793
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
20
|
| pubmed:volume |
314
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
471-7
|
| pubmed:dateRevised |
2007-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:3456079-Adolescent,
pubmed-meshheading:3456079-Analysis of Variance,
pubmed-meshheading:3456079-Child,
pubmed-meshheading:3456079-Child, Preschool,
pubmed-meshheading:3456079-DNA, Neoplasm,
pubmed-meshheading:3456079-Dose-Response Relationship, Drug,
pubmed-meshheading:3456079-Female,
pubmed-meshheading:3456079-Flow Cytometry,
pubmed-meshheading:3456079-Hemoglobins,
pubmed-meshheading:3456079-Humans,
pubmed-meshheading:3456079-Infant,
pubmed-meshheading:3456079-Infusions, Parenteral,
pubmed-meshheading:3456079-Leukemia, Lymphoid,
pubmed-meshheading:3456079-Leukocyte Count,
pubmed-meshheading:3456079-Male,
pubmed-meshheading:3456079-Metabolic Clearance Rate,
pubmed-meshheading:3456079-Methotrexate,
pubmed-meshheading:3456079-Prospective Studies,
pubmed-meshheading:3456079-Random Allocation,
pubmed-meshheading:3456079-Recurrence
|
| pubmed:year |
1986
|
| pubmed:articleTitle |
Clinical pharmacodynamics of high-dose methotrexate in acute lymphocytic leukemia. Identification of a relation between concentration and effect.
|
| pubmed:publicationType |
Journal Article,
Clinical Trial,
Research Support, U.S. Gov't, P.H.S.,
Randomized Controlled Trial,
Research Support, Non-U.S. Gov't
|