Postinduction dexamethasone and individualized dosing of escherichia coli l-asparaginase each improve outcome of children and adolescents with newly diagnosed acute lymphoblastic leukemia: Results from a randomized study - Dana-Farber Cancer Institute ALL Consortium Protocol 00-01

Lynda M. Vrooman, Kristen E. Stevenson, Jeffrey G. Supko, Jane O'Brien, Suzanne E. Dahlberg, Barbara L. Asselin, Uma H. Athale, Luis A. Clavell, Kara M. Kelly, Jeffery L. Kutok, Caroline Laverdière, Steven E. Lipshultz, Bruno Michon, Marshall Schorin, Mary V. Relling, Harvey J. Cohen, Donna S. Neuberg, Stephen E. Sallan, Lewis B. Silverman

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173 Scopus citations

Abstract

Purpose: We assessed the toxicity and efficacy of dexamethasone and a novel dosing method of Escherichia coli L-asparaginase (EC-Asnase) in children and adolescents with newly diagnosed acute lymphoblastic leukemia (ALL) Patients and Methods: Patients achieving complete remission (CR) on Dana-Farber Cancer Institute ALL Consortium Protocol 00-01 were eligible for random assignment to 1) dexamethasone or prednisone, administered as 5-day pulses, every 3 weeks, and 2) weekly EC-Asnase, administered as a 25,000 U/m2 fixed dose (FD) or individualized dose (ID) starting at 12,500-IU/m2, adjusted every 3 weeks based on nadir serum asparaginase activity (NSAA) determinations Results: Between 2000 and 2004, 492 evaluable patients (ages 1 to 18 years) enrolled; 473 patients (96%) achieved CR. Four hundred eight patients (86%) participated in the corticosteroid randomization and 384 patients (81%) in the EC-Asnase randomization. With 4.9 years of median follow-up, dexamethasone was associated with superior 5-year event-free survival (EFS; 90% v 81% for prednisone; P = .01) but higher rates of infection (P = .03) and, in older children, higher cumulative ncidence of osteonecrosis (P = .02) and fracture (P = .06). ID EC-Asnase had superior 5-year EFS (90% v 82% for FD; P = .04), but did not reduce the frequency of asparaginase-related toxicity. Multivariable analysis identified both dexamethasone and ID EC-Asnase as independent predictors of favorable EFS. Conclusion: There was no overall difference in skeletal toxicity by corticosteroid type; dexamethasone was associated with more infections and, in older children, increased incidence of osteonecrosis and fracture. There was no difference in asparaginase-related toxicity by EC-Asnase dosing method Dexamethasone and ID EC-Asnase were each associated with superior EFS. Monitoring NSAA during treatment with EC-Asnase may be an effective strategy to improve outcome in pediatric ALL.

Original languageEnglish (US)
Pages (from-to)1202-1210
Number of pages9
JournalJournal of Clinical Oncology
Volume31
Issue number9
DOIs
StatePublished - Mar 20 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Vrooman, L. M., Stevenson, K. E., Supko, J. G., O'Brien, J., Dahlberg, S. E., Asselin, B. L., Athale, U. H., Clavell, L. A., Kelly, K. M., Kutok, J. L., Laverdière, C., Lipshultz, S. E., Michon, B., Schorin, M., Relling, M. V., Cohen, H. J., Neuberg, D. S., Sallan, S. E., & Silverman, L. B. (2013). Postinduction dexamethasone and individualized dosing of escherichia coli l-asparaginase each improve outcome of children and adolescents with newly diagnosed acute lymphoblastic leukemia: Results from a randomized study - Dana-Farber Cancer Institute ALL Consortium Protocol 00-01. Journal of Clinical Oncology, 31(9), 1202-1210. https://doi.org/10.1200/JCO.2012.43.2070