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Impact of high-dose cytarabine and asparaginase intensification on childhood acute myeloid leukemia: a report from the Childrens Cancer Group.

Author(s): Wells RJ, Woods WG, Lampkin BC, Nesbit ME, Lee JW, Buckley JD, Versteeg C, Hammond GD

Affiliation(s): Children's Hospital Research Foundation, Cincinnati, OH.

Publication date & source: 1993-03, J Clin Oncol., 11(3):538-45.

Publication type: Clinical Trial; Randomized Controlled Trial

PURPOSE: The purpose of this review was to determine the impact of high-dose cytarabine and asparaginase intensification, administered shortly after remission induction, on the outcome of childhood acute myeloid leukemia (AML). MATERIALS AND METHODS: Three consecutive Childrens Cancer Group (CCG) trials of acute myeloid leukemia, CCG 251 (1979 to 1983), CCG 213P (1983 to 1985), and CCG 213 (1985 to 1989) with a total of 1,294 patients, were reviewed and provide the basis of this report. RESULTS: CCG 213P demonstrated the importance of dose interval, in that two courses of cytarabine and asparaginase administered at 7-day intervals gave superior 5-year survival rates (58% v 41% from the end of induction, P < .04) to the same therapy administered at 28-day intervals. CCG 213 showed that there was no advantage to the maintenance therapy used for patients who received two courses of cytarabine and asparaginase at 7-day intervals (5-year survival, 68% [no maintenance] v 44% [maintenance] from the end of consolidation, P < .01). Inclusion of the 7-day interval cytarabine/asparaginase intensification was accompanied by an overall improvement in 5-year survival rates from diagnosis when compared with historical controls (CCG 213, 36% v CCG 251, 29%, P < .02) although other differences between these studies could also be responsible for the improvement seen. CONCLUSION: High-dose cytarabine and asparaginase intensification eliminated the benefit of prolonged maintenance therapy in childhood AML and was accompanied by an overall improvement in survival.

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