Document Detail

Methotrexate-induced alterations in beta-oxidation correlate with cognitive abilities in children with acute lymphoblastic leukemia.
MedLine Citation:
PMID:  18398226     Owner:  NLM     Status:  MEDLINE    
Treatment advances, including central nervous system (CNS) treatment with methotrexate, have led to significant gains in disease-free survival from childhood acute lymphoblastic leukemia (ALL). However, methotrexate has been associated with neurological problems such as declines in cognitive and academic abilities. The purpose of this study was to investigate methotrexate-induced changes in beta-oxidation in children with ALL receiving methotrexate for CNS treatment. Specific aims were to investigate effects of methotrexate on beta-oxidation of the two most prevalent fatty acids (palmitic acid and stearic acid) in cerebrospinal fluid (CSF) samples and correlate the ratio of monounsaturation to saturation of these fatty acids with cognitive and academic abilities. The sample included 12 females and 14 males with low-risk (n = 7), standard-risk ( n = 13), or high-risk (n = 6) ALL. Mean age at diagnosis was 94.1 months (SD = 34.4). CSF samples were obtained in conjunction with diagnostic lumbar punctures; subsequent samples were obtained prior to intrathecal methotrexate administration during the induction, consolidation, and continuation phases of treatment. Fatty acids were analyzed by gas chromatography. Results showed a significant increase in the ratio of monounsaturation to saturation of both fatty acids, which was greatest during the most intensive phase of treatment. Ratios of monounsaturated to saturated fatty acids were negatively correlated with full-scale IQ, verbal IQ, and math calculations. Findings suggest that methotrexate alters beta-oxidation and that the resulting increase in fatty acid monounsaturation is related to declines in some domains of cognitive ability.
Ida M Ki Moore; Petra Miketova; Marilyn Hockenberry; Kevin Krull; Alice Pasvogel; Marissa Carey; Kris Kaemingk
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Biological research for nursing     Volume:  9     ISSN:  1099-8004     ISO Abbreviation:  Biol Res Nurs     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-04-09     Completed Date:  2008-05-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9815758     Medline TA:  Biol Res Nurs     Country:  United States    
Other Details:
Languages:  eng     Pagination:  311-9     Citation Subset:  IM; N    
College of Nursing, University of Arizona, Tucson, AZ 85721-0203, USA.
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MeSH Terms
Analysis of Variance
Antimetabolites, Antineoplastic / adverse effects*
Chromatography, Gas
Cognition Disorders / cerebrospinal fluid,  chemically induced*,  diagnosis,  metabolism
Intelligence Tests
Methotrexate / adverse effects*
NAD / antagonists & inhibitors,  drug effects
Oxidation-Reduction / drug effects
Palmitic Acid* / cerebrospinal fluid,  metabolism
Precursor Cell Lymphoblastic Leukemia-Lymphoma / complications,  drug therapy*
Psychomotor Performance
Risk Factors
Statistics, Nonparametric
Stearic Acids* / cerebrospinal fluid,  metabolism
Grant Support
Reg. No./Substance:
0/Antimetabolites, Antineoplastic; 0/Stearic Acids; 53-84-9/NAD; 57-10-3/Palmitic Acid; 59-05-2/Methotrexate

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