Prolonged Methotrexate Infusions in Children with Acute Leukemia in Relapse and in Remission and with Medulloblastoma

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Abstract
In 86 children with acute lymphocytic leukemia (ALL) and in 6 children with medulloblastoma 253 24-h methotrexate (MTX) infusions with 150, 500, and 700 mg/m2 were performed. MTX concentrations in plasma and CSF were measured with a specific radioimmunoassay. In 131 infusions with 500 mg/m2 given to patients with ALL in remission, the MTX plasma concentration 24 h after the end of infusion did not exceed 7 .times. 10-7 mol/l. Mild hematologic toxicity occurred in 22% of the treatment cycles. In contrast 8/45 infusions given to patients with ALL in relapse were associated with delayed MTX elimination followed by severe toxicity. The CSF:plasma ratio of MTX measured during 58 infusions did not exceed 11% in patients with ALL in remission, but was above this value in 13/34 infusions in patients with leukemia of CNS; 24-h MTX infusions with 500 mg/m2 were as hepatotoxic as 4- to 6-h infusions with 3-8.5 g/m2. With MTX as single agent no remissions were achieved in 8 patients with ALL in relapse. The addition of asparaginase in 10 patients resulted in 3 complete and 2 partial remissions. In patients with ALL in 1st remission clinical results confirmed the value of intensive MTX therapy for disease-free survival.