Meningeal leukemia is an important complication of acute leukemia.3 While chemotherapy has resulted in prolongation of survival,4 the effective antimetabolites do not reach therapeutic levels in the cerebrospinal fluid.5,6 As a result, meningeal leukemia has become the major therapeutic problem in patients with acute leukemia in remission, as well as being a serious complication encountered in patients with active leukemia.3
Intrathecal methotrexate (Amethopterin) has been used for the treatment of meningeal leukemia.7-9 At dosages usually employed, this therapy has often been adequate to control symptoms. However, in cases which do not respond, further increments in dosage have been limited by concern regarding neurotoxicity. Wollner et al. described seizures in dogs following 1.0-1.5 mg. per kilogram of methotrexate administered by cisternal injection.10 Moreover, neurotoxicity of folic acid antagonists related to the quantity of pteroylglutamic acid, not to the antifolic activity of the compound.10 Therefore,
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