The addition of methotrexate to treatment protocols in children with acute lymphoblastic leukemia has been found beneficial in preventing central nervous system relapse. However, MTX[1] itself may be associated with neurologic morbidities, the most significant of which is leukoencephalopathy. The present study describes the clinical spectrum of leukoencephalopathy, which ranges from a subclinical disease manifested only radiologically to a progressive, devastating encephalopathy. The interaction of MTX with other components of the treatment protocol is discussed, as is the effect of leucovorin. A summary is presented of the metabolic pathways that may be involved in the development of MTX toxicity. Researchers are still seeking a biochemical marker to aid in the determination of the amount of MTX that may be safely administered.

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