Remission Maintenance Therapy for Meningeal Leukemia: Intrathecal Methotrexate vs. Intravenous bis-Nitrosourea

Abstract

Central nervous system infiltrates have become a major cause of morbidity among leukemic children and may constitute a site from which a remission marrow is again infiltrated. Conventional intrathecal methotrexate (IT MTX) therapy produces excellent palliation and complete reversal of abnormal cerebrospinal fluid findings for periods ranging from 6 to 414 days (median 87 days). The CNS remission maintenance potential of (1) IT MTX, 12 mg/sq m, every 6-8 wk, and (2) bis-nitrosourea (BCNU), 100 mg/sq m intravenously, every 6-8 wk were compared with "no therapy" maintenance. Only those children in CNS remission 6-8 wk following induction therapy were eligible for randomization to the maintenance study. The duration of CNS remission for BCNU-maintained and "no therapy" patients was similar, with a median length of remission of 96 days and 112 days, respectively. The median duration of remission for the MTX maintenance group was 472 days. The differences in length of CNS remission between the MTX group and the other two groups were statistically highly significant (p < 0.01 for both comparisons). Headache, fever, and/or vomiting occurred in 38% of the children after one or more of the intrathecal maintenance treatments and, in general, symptoms tended to worsen as maintenance continued.