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

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Asparaginase
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Dexamethasone
Escherichia coli
Neoplasms
Osteonecrosis
Random Allocation
Prednisone
Adrenal Cortex Hormones
Infection
Serum
Disease-Free Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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

In: Journal of Clinical Oncology, Vol. 31, No. 9, 20.03.2013, p. 1202-1210.

Research output: Contribution to journalArticle

Vrooman, LM, Stevenson, KE, Supko, JG, O'Brien, J, Dahlberg, SE, Asselin, BL, Athale, UH, Clavell, LA, Kelly, KM, Kutok, JL, Laverdière, C, Lipshultz, SE, Michon, B, Schorin, M, Relling, MV, Cohen, HJ, Neuberg, DS, Sallan, SE & Silverman, LB 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, vol. 31, no. 9, pp. 1202-1210. https://doi.org/10.1200/JCO.2012.43.2070
Vrooman, Lynda M. ; Stevenson, Kristen E. ; Supko, Jeffrey G. ; O'Brien, Jane ; Dahlberg, Suzanne E. ; Asselin, Barbara L. ; Athale, Uma H. ; Clavell, Luis A. ; Kelly, Kara M. ; Kutok, Jeffery L. ; Laverdière, Caroline ; Lipshultz, Steven E ; Michon, Bruno ; Schorin, Marshall ; Relling, Mary V. ; Cohen, Harvey J. ; Neuberg, Donna S. ; Sallan, Stephen E. ; Silverman, Lewis B. / 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. In: Journal of Clinical Oncology. 2013 ; Vol. 31, No. 9. pp. 1202-1210.
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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.",
author = "Vrooman, {Lynda M.} and Stevenson, {Kristen E.} and Supko, {Jeffrey G.} and Jane O'Brien and Dahlberg, {Suzanne E.} and Asselin, {Barbara L.} and Athale, {Uma H.} and Clavell, {Luis A.} and Kelly, {Kara M.} and Kutok, {Jeffery L.} and Caroline Laverdi{\`e}re and Lipshultz, {Steven E} and Bruno Michon and Marshall Schorin and Relling, {Mary V.} and Cohen, {Harvey J.} and Neuberg, {Donna S.} and Sallan, {Stephen E.} and Silverman, {Lewis B.}",
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T1 - Postinduction dexamethasone and individualized dosing of escherichia coli l-asparaginase each improve outcome of children and adolescents with newly diagnosed acute lymphoblastic leukemia

T2 - Results from a randomized study - Dana-Farber Cancer Institute ALL Consortium Protocol 00-01

AU - Vrooman, Lynda M.

AU - Stevenson, Kristen E.

AU - Supko, Jeffrey G.

AU - O'Brien, Jane

AU - Dahlberg, Suzanne E.

AU - Asselin, Barbara L.

AU - Athale, Uma H.

AU - Clavell, Luis A.

AU - Kelly, Kara M.

AU - Kutok, Jeffery L.

AU - Laverdière, Caroline

AU - Lipshultz, Steven E

AU - Michon, Bruno

AU - Schorin, Marshall

AU - Relling, Mary V.

AU - Cohen, Harvey J.

AU - Neuberg, Donna S.

AU - Sallan, Stephen E.

AU - Silverman, Lewis B.

PY - 2013/3/20

Y1 - 2013/3/20

N2 - 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.

AB - 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.

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