Combination intrathecal (IT) therapy for meningeal leukemia: two versus three drugs

Abstract

Principles of combination chemotherapy were applied to intrathecal (IT) therapy for meningeal leukemia in a randomized study in children. Diagnosis required a cerebral spinal fluid (CSF) mononuclear cell count ≥ 10 mm3 or blast cells in any number. Children in marrow remission and relapse were randomized separately. Two drug therapy consisted of methotrexate 15 mg/M2 + hydrocortisone 15 mg/M2, IT, every 4 to 5 days, until the CSF normalized, followed by maintenance therapy, instituted leukovorin 2 wk and continuing at increasing intervals to 8 wk, to central nervous system (CNS) relapse or death. Three drug therapy added cytosar 30 mg/M2 IT to each treatment as above. All were given keukovorin with each treatment. The median length of CNS remission was 460 days for the 3 drug therapy (N=48) and 317 days for the 2 drug therapy (N=45), p=0.25. Three triple therapy patients in CNS remission had not reached the median at the time of report, all continuing 2 drug patients had passed the median. Triple therapy patients in marrow relapse had not reached their median; the median length of CNS remission for 2 drug patients in marrow relapse was 176 days. Toxicities of the regimens were similar.