Central nervous system (CNS) relapse is reported in three children with acute lymphocytic leukemia who received intermittent prophylactic CNS therapy with intrathecal methotrexate. The children were on monochemotherapy either with methotrexate or 6-mercaptopurine for 21/2 years. The CNS relapse occurred 21/2, 10 and 11 months after cessation of all chemotherapy. Irradiation and/or intensive chemotherapy including drugs as BCNU and Ara-C which are known to cross the blood-brain barrier were not given. Preventive CNS radiotherapy should be considered in all children who did not receive an adequate prophylactic CNS therapy even after long-term remission before chemotherapy is stopped.

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