Remission induction of meningeal leukemia with high-dose intravenous methotrexate.

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Abstract
Twenty children with acute lymphoblastic leukemia who developed meningeal disease were treated with a high-dose i.v. methotrexate regimen that was designed to achieve and maintain CSF methotrexate concentrations of 10-5 mol/l without the need from concomitant intrathecal dosing. The methotrexate was administered as a loading dose of 6,000 mg/m2 for a period of 1 h followed by an infusion of 1,200 mg/m2h for 23 h. Leucovorin rescue was initiated 12 h after the end of the infusion with a loading dose of 200 mg/m2 followed by 12 mg/m2 every 3 h for 6 doses and then every 6 h until the plasma methotrexate level decreased to < 1 .times. 10-7 mol/l. The mean steady-state plasma and CSF methotrexate concentrations achieved were 1.1 x 10-3 mol/l and 3.6 x 10-5 mol/l, respectively. All 20 patients responded to this regimen, 16/20 (80%) achieved a complete remission and 20% obtained a partial remission. The most common toxicities encountered were transient serum transaminase and bilrubin elevations, neutropenia and mucositis. One patient had focal seizures and transient hemiparesis but recovered completely. High-dose i.v. methotrexate is an effective treatment for the induction of remission after meningeal relapse in acute lymphoblastic leukemia.

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