Changes of cerebral biopterin and biogenic amine metabolism in leukemic children receiving 5 g/m2 intravenous methotrexate

Pediatric Research
F MillotF Guilhot

Abstract

Acute or subacute neurologic disorders can be observed in patients receiving high-dose methotrexate therapy for lymphoblastic leukemia or malignant tumor. Impairment of biopterin metabolism leading to decreased availability of monoamine neurotransmitters has been suggested to explain methotrexate neurotoxicity. To investigate such a mechanism, we have measured prospectively by HPLC the concentrations of total biopterin, homovanillic acid, and 5-hydroxyindolacetic acid in cerebrospinal fluid of 57 children with acute lymphoblastic leukemia. A sequential analysis of cerebrospinal fluid was performed for each patient: cerebrospinal fluid samples were obtained before therapy and after each of the four high-dose methotrexate infusions during the CNS prophylaxis phase. A significant increase of total biopterin concentrations in cerebrospinal fluid was observed after high-dose methotrexate therapy compared with the pretreatment values. No cumulative effect was noted. In contrast, no significant variation of the homovanillic acid and 5-hydroxyindolacetic acid levels was observed in cerebrospinal fluid. However, individual analysis revealed a transient decrease of homovanillic acid and 5-hydroxyindolacetic acid concentrations in cerebro...Continue Reading

Citations

May 29, 2004·Journal of Pediatric Hematology/oncology·Charles T QuinnNaomi J Winick
Jul 3, 2010·AJNR. American Journal of Neuroradiology·B PaudyalM Skliut
May 9, 2002·Journal of Magnetic Resonance Imaging : JMRI·Minna J MäkirantaOsmo Tervonen
Feb 5, 2000·Journal of Neurosurgery·R I JakackiT G Luerssen
Oct 3, 2002·American Journal of Medical Genetics·M Michael Cohen
Sep 1, 2009·Rapid Communications in Mass Spectrometry : RCM·Tomiko KuharaKenji Omura
Oct 30, 2019·International Journal of Molecular Sciences·Yosra BedouiPhilippe Gasque
Apr 3, 2001·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·F MillotUNKNOWN Children's Leukemia Cooperative Group of the European Organiztaion for Research and Treatment of Cancer
Dec 20, 2002·Canadian Journal of Physiology and Pharmacology·Sampath MadhyasthaK Laxminarayana Bairy

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