title: Central nervous system prophylaxis with high-dose methotrexate does not give rise to significant electroencephalographic changes in children with acute lymphoblastic leukemia.
abstract: Acute, subacute, and chronic neurologic complications have been reported in children treated with high-dose methotrexate for various malignant diseases. It was the aim of this study to monitor central nervous system treatment with high-dose methotrexate in children with acute lymphoblastic leukemia by serial electroencephalographic (EEG) examinations. Electroencephalographic examinations with quantitative computed analysis were performed in 21 children before and on the third day after each of four high-dose methotrexate infusions with leucovorin rescue according to protocol M of trial ALL-BFM 90 of the German Society for Pediatric Haematology and Oncology. Six patients with a medium risk of relapse also received L-asparaginase. In the cohort treated with methotrexate solely, no statistically significant changes of the quantitative EEG parameters could be demonstrated. Only two children with delayed serum methotrexate clearance showed reversible diffuse EEG slowing of a slight to moderate degree. In the group with additional L-asparaginase treatment, slight transient EEG slowing also occurred. Our findings indicate that in patients with a normal methotrexate clearance during central nervous system treatment with high-dose methotrexate according to trial BFM-ALL 90, usually no subacute or cumulative EEG changes have to be expected. If neurologic or psychiatric symptoms or EEG slowing occur, delayed methotrexate clearance must be suspected.
authors.affiliation: Department of Neuropediatrics and Muscular Disorders, Pediatric University Hospital, Freiburg, Germany. rudokori@kikli.ukl.uni-freiburg.de
authors.forename: Rudolf
authors.initials: R
authors.lastname: Korinthenberg
authors.forename: Annette
authors.initials: A
authors.lastname: Schneider
authors.forename: Charlotte
authors.initials: C
authors.lastname: Niemeyer
mesh_terms: D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001215:Asparaginase / Q000008:administration & dosage; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D016543:Central Nervous System Neoplasms / Q000503:physiopathology / Q000517:prevention & control*; D002648:Child; D002675:Child, Preschool; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D006801:Humans; D007223:Infant; D007275:Injections, Intravenous; D007278:Injections, Spinal; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D000964:Antimetabolites, Antineoplastic; D001215:Asparaginase; D002955:Leucovorin; D008727:Methotrexate