Central nervous system infiltration was studied in a group of 47 children with acute leukemia. CNS involvement was found to occur more frequently and appear more rapidly in patients who presented with elevated peripheral WBC counts. CNS infiltration not suspected clinically was identified by spinal fluid examination in a significant minority of children at the time of the initial diagnosis of leukemia, indicating that lumbar puncture should be a routine part of the initial evaluation of patients with acute leukemia. Intrathecal amethopterin administered "prophylactically" at the time of initial diagnosis of leukemia did not prevent or decrease the frequency of occurrence of CNS infiltration. However, it did delay the onset of CNS involvement in patients with elevated WBC counts. Intrathecal amethopterin administered before the onset of CNS infiltration appears to be useful in delaying morbidity resulting from CNS involvement in children who present with elevated peripheral WBC counts.

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