Observations on the course of 59 children who experienced 109 distinct episodes of CNS involvement by leukemia showed that: 1. This complication may be associated with all types of acute and subacute leukemia. 2. There is no single or combination of diagnostic criteria. Manifestations of increased CSF pressure, such as vomiting, headache, and papilledema are the most frequent clinical findings. However, it should be emphasized that CNS involvement may be associated with normal CSF findings. 3. CNS involvement may be present at the onset of leukemia or can occur at any time during the course. 4. Approximately 26 per cent of children with leukemia develop CNS involvement. 5. CNS involvement may occur when the disease is under apparently good therapeutic control as well as during relapse. 6. There is no relationship between the agents which had been previously used to treat the systemic disease and the later development of CNS involvement. However, the onset of CNS symptoms was less frequent when the systemic disease was under treatment with steroids. 7. The development of CNS involvement does not appear to shorten the survival time of patients with leukemia when treatment for CNS involvement is given.

1. Thirty-six children with leukemic involvement of the CNS were treated with one to seven courses of methotrexate given intrathecally. a. Complete or partial symptomatic relief occurred in 57 of 67 episodes treated. b. Onset of improvement ranged from immediately after the initial lumbar puncture to 18 days later. c. Duration of response, with complete relief from symptoms, ranged from eight to 751 + days, median 84 days. d. Median values for CSF pressure, white cell count, and sugar were abnormal during therapy but were normal one week after therapy was complete. In individual episodes, abnormalities persisted longer. e. Systemic toxicity was infrequent. f. CNS leukemia has the same sensitivity or resistance to intrathecal methotrexate as the systemic disease had when initially treated with oral methotrexate. The response of CNS leukemia to intrathecal methotrexate may be predicted by the responsiveness of the systemic disease when initially treated with oral methotrexate. g. Intrathecal methotrexate may still be effective therapy for CNS leukemia in patients whose systemic disease was initially sensitive but later developed resistance to oral methotrexate. 2. Symptoms due to CNS leukemia may respond to lumbar puncture without the injection of medication. Symptomatic improvement was observed within 48 hours and lasted from 23 to 110 days in a small number of patients not given intrathecal methotrexate therapy. However, lumbar puncture per se did not significantly alter the abnormal CSF findings.