Cerebrospinal fluid biogenic amine metabolites in children during treatment for acute lymphocytic leukemia

Faye S. Silverstein, Raymond J. Hutchinson, Michael V Johnston

Research output: Contribution to journalArticle

Abstract

To learn more about the impact of intrathecal methotrexate and cystosine arabinoside therapy on neuronal metabolism, we measured serial cerebrospinal fluid concentrations of homovanillic acid and 5-hydroxyindole-acetic acid, major metabolites of the neurotransmitters dopamine and serotonin, in children with acute lymphocytic leukemia. Multiple sequential cerebrospinal fluids were obtained from 30 children with acute lymphocytic leukemia evaluated prospectively from the time of diagnosis. We focused on the period of induction and intensification when children received weekly intrathecal chemotherapy. Paired cerebrospinal fluid specimens were also obtained at 3-month intervals from 60 children with acute lymphocytic leukemia in remission. Homovanillic acid and 5-hydroxyin-doleacetic acid were measured using high performance liquid chromotography with electrochemical detection. We found that pretreatment metabolite values were no different from those in age-matched subjects in remission. In the first 5 wk of treatment, there were no significant changes in metabolite levels in patients treated exclusively with methotrexate. There was a transient decrease in homovanillic acid (-28 ± 10%, p <0.001, Student's t test) and 5-hydroxyindoleacetic acid (—28 ± 12%, p <0.05) in five of six patients after a single intrathecal dose of cytosine arabinoside. In the next 4 wk there was a gradual rise in levels of homovanillic acid (p = 0.001, by analysis of variance) and 5-hydroxyindoIeacetic acid (p = 0.029, analysis of variance); this pattern did not correlate with administration of cranial irradiation. In children in remission, there were no significant changes in metabolite levels over a 3-month period. The data suggest that intensive therapy including methotrexate and cytosine arabinoside alters central neurotransmitter metabolism and/or transport in children with acute lymphocytic leukemia.

Original languageEnglish (US)
Pages (from-to)285-291
Number of pages7
JournalPediatric Research
Volume20
Issue number4
StatePublished - 1986
Externally publishedYes

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Biogenic Amines
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Cerebrospinal Fluid
Homovanillic Acid
Methotrexate
Cytarabine
Neurotransmitter Agents
Analysis of Variance
Therapeutics
Cranial Irradiation
Hydroxyindoleacetic Acid
Acids
Acetic Acid
Dopamine
Serotonin
Students
Drug Therapy

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Cerebrospinal fluid biogenic amine metabolites in children during treatment for acute lymphocytic leukemia. / Silverstein, Faye S.; Hutchinson, Raymond J.; Johnston, Michael V.

In: Pediatric Research, Vol. 20, No. 4, 1986, p. 285-291.

Research output: Contribution to journalArticle

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