Transient Encephalopathy during the Intensive Chemotherapy with High-Dose Methotrexate in Children with Acute Lymphocytic Leukemia

Abstract

Severe neurological complications during and after chemotherapy were surveyed in 426 patients with acute lymphocytic leukemia (ALL) who were registered in the Children's Cancer and Leukemia Study Group (CCLSG) during 1981 to 1987. Eleven of the 426 cases developed neurological dysfunction or encephalopathy. Seven patients with overt central nervous system (CNS) leukemia, treated with frequent intrathecal methotrexate (MTX) and/or skull irradiation, developed seizure, ataxia, and gradually an unconscious condition, and were diagnosed as having necrotizing leukoencephalopathy. However, four patients out of 11 cases who received early consolidation therapy with 3 courses of high-dose MTX (1.5-6.0 g/m² with 24-hour infusion) and intrathecal MTX (15 mg/m² for 6 doses) for CNS-prophylaxis, developed temporary neurological complications, such as abrupt episodes of convulsion and loss of consciousness. All neurological abnormalities, including transient, nonspecific abnormalities in CT scan and EEG findings, recovered to normal within 30 days without any sequelae. After the modification of dosage and number of intrathecal injections of MTX (reduced to 12 mg/m² for one dose), these neurological complications were not observed. These data suggested that transient subacute neurotoxicities of MTX had a mechanism that was not similar to necrotizing leukoencephalophathy.