Cerebrospinal Fluid Biogenic Amine Metabolites in Children during Treatment for Acute Lymphocytic Leukemia

Abstract

To learn more about the impact of intrathecal methotrexate and cytosine arabinoside therapy on neuronal metabolism, we measured serial cerebrospinal fluid concentrations of homovanillic acid and 5-hydroxyindoleacetic 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-hydroxyindoleacetic acid were measured using high performance liquid chromatography 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 less than 0.001, Student's t test) and 5-hydroxyindoleacetic acid (-28 +/- 12%, p less than 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-hydroxyindoleacetic 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.(ABSTRACT TRUNCATED AT 250 WORDS)