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Isr Med Assoc J. 2002 Nov;4(11):1050-3.

Methotrexate-related neurotoxicity in the treatment of childhood acute lymphoblastic leukemia.

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Department of Pediatric Oncology-Hematology, Schneider Children's Medical Center of Israel, Petah Tiqva, Israel.


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 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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