Related Experiment Video
Updated: Aug 16, 2026
Comprehensive DNA Methylation Analysis Using a Methyl-CpG-binding Domain Capture-based Method in Chronic Lymphocytic Leukemia Patients
Published on: June 16, 2017
Central nervous system prophylaxis with high-dose methotrexate does not give rise to significant
Rudolf Korinthenberg1, Annette Schneider, Charlotte Niemeyer
1Department of Neuropediatrics and Muscular Disorders, Pediatric University Hospital, Freiburg, Germany. rudokori@kikli.ukl.uni-freiburg.de
Insights
High-dose methotrexate for childhood leukemia rarely causes significant EEG changes in children with normal clearance. Delayed methotrexate clearance may lead to reversible EEG slowing, indicating potential neurotoxicity.
Area of Science:
- Pediatric Oncology
- Neuroscience
- Pharmacology
Background:
- High-dose methotrexate (HD-MTX) is crucial for treating childhood acute lymphoblastic leukemia (ALL).
- Neurologic complications, including acute, subacute, and chronic, are known adverse effects of HD-MTX.
- Serial electroencephalographic (EEG) examinations are valuable for monitoring central nervous system (CNS) effects.
Purpose of the Study:
- To monitor CNS treatment effects of HD-MTX in pediatric ALL patients using serial EEG.
- To investigate potential subacute or cumulative EEG changes during HD-MTX therapy.
Main Methods:
- Quantitative EEG analysis was performed on 21 children with ALL before and after HD-MTX infusions (protocol M, ALL-BFM 90).
- Patients received HD-MTX with leucovorin rescue; six also received L-asparaginase.
- EEG parameters were assessed quantitatively after each of four HD-MTX infusions.
Main Results:
- No statistically significant changes in quantitative EEG parameters were observed in patients treated solely with methotrexate.
- Two children with delayed methotrexate clearance showed reversible, mild to moderate diffuse EEG slowing.
- Slight, transient EEG slowing occurred in the group receiving additional L-asparaginase.
Conclusions:
- Normal methotrexate clearance during HD-MTX CNS treatment in pediatric ALL (BFM-ALL 90 protocol) is generally not associated with subacute or cumulative EEG changes.
- The occurrence of neurologic symptoms or EEG slowing warrants suspicion of delayed methotrexate clearance.
- EEG monitoring can help identify potential neurotoxicity related to methotrexate clearance issues.
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.
