Delay of the diagnostic lumbar puncture and intrathecal chemotherapy in children with acute lymphoblastic leukemia who undergo routine corticosteroidtesting: Tokyo Children's Cancer Study Group study L89-12

Purpose: To determine the effects of eliminating initial lumbar punctures i n 418 consecutively treated children with acute lymphoblastic leukemia (ALL ). Patients and Methods: Patients were enrolled onto a trial conducted in cent ral Japan between 1989 and 1992. Treatment consisted of standard four-drug induction therapy followed by a risk-based intensification phase, reinducti on therapy, late intensification, and remission maintenance therapy (total of 104 weeks). The initial lumbar puncture, with an intrathecal injection o f chemotherapy, was performed after 1 week of prednisolone sensitivity test ing (day 8). End points included response to prednisolone, CNS status at th e time of the day 8 lumbar puncture, subsequent adverse events in CNS and b one marrow, and event-free survival (EFS). Results: The remission induction rate was 93.1% with a 6-year EFS rate (+/- SE) of 68.7% +/- 2.4%, which is similar to historical results for patients who received their-diagnostic lumbar puncture and first instillation of in trathecal chemotherapy on day 0. Overall, 84.5% of the patients had good re sponses to prednisolone, whereas 15.5% had poor responses. Clinical outcome was strikingly better for the good responders (6-year EFS, 74.1% +/- 2.5% compared with 40.1% +/- 6.4% for patients with poor responses), suggesting that omission of intrathecal chemotherapy did not alter the predictive valu e of drug sensitivity testing. Eighteen patients experienced CNS relapse as their first adverse event (cumulative risk, 5.1%; 95% confidence interval, 2.7% to 7.4%), coincident with reports from groups using conventional stra tegies of CNS clinical management. Bleeding into the CSF at the time of the day 8 lumbar puncture was apparent in 29 cases (8.1%), but leukemic blasts were identified in only two. Conclusion: Delay of the initial lumbar puncture and intrathecal injection of chemotherapy seems to be feasible in children with ALL. Further controll ed evaluations are needed to establish the validity of this conclusion. (C) 2001 by American Society of Clinical Oncology.