Rationale: Leukoencephalopathy, a complication associated with chemotherapy has been reported after giving high doses of methotrexate and cytarabine with no specific risk factors to date.

Objectives:
1. To review the prevalence of chemotherapy-induced leukoencephalopathy in children with acute lymphoblastic leukemia (ALL).
2. To present the clinical course, pathogenesis and neuro-imaging findings of chemotherapy-induced leukoencephalopathy in children with ALL.

Case: We reported three cases of adolescent ALL precursor B-cell patients who received high doses of methotrexate and presented with neurologic and MRI findings consistent with leukoencephalopathy. Our patients were only placed on supportive measures with adequate hydration, without providing any special intervention. Yet, all of them had complete neurological recovery.

Discussion and Summary: Methotrexate is a cell cycle-specific agent that inhibits the enzyme dihydrofolate reductase, preventing the conversion of folic acid to tetrahydrofolic acid and inhibiting cell replication. It is one of the most commonly implicated drug causing leukoencephalopathy. [3] On MRI T2-weighted images, all of them had hyperintensities on the posterior frontal/parietal corona radiata and centrum semiovale consistent with leukoencephalopathy. Complete recovery happened spontaneously in all of the cases. There is no standard treatment for acute and subacute toxicities from methotrexate.