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

doi:10.1200/JCO.2012.43.2070

Back

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 article

Open access

Peer reviewed

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, …

Journal of clinical oncology, Vol.31(9), pp.1202-1210

2013-03-20

DOI: https://doi.org/10.1200/JCO.2012.43.2070

PMCID: PMC3595424

PMID: 23358966

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 IU/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 incidence 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.

Files and links (1)

url

https://doi.org/10.1200/JCO.2012.43.2070View

Published (Version of record) Open

Metrics

61 Record Views

246 Times Cited - Web of Science

See more details

InCites Highlights

These are selected metrics from InCites Benchmarking & Analytics tool, related to this output

Collaboration types: Industry collaboration; Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.103 Blood Disorders; 1.103.155 Acute Myeloid Leukemia
Web Of Science research areas: Oncology
ESI research areas: Clinical Medicine

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Source: InCites

Details

Title: 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
Creators: Lynda M Vrooman - Lynda M. Vrooman, Kristen E. Stevenson, Jane O'Brien, Suzanne Dahlberg, Donna S. Neuberg, Stephen E. Sallan, and Lewis B. Silverman, Dana-Farber Cancer Institute; Lynda M. Vrooman, Stephen E. Sallan, and Lewis B. Silverman, Boston Children's Hospital; Jeffrey G. Supko, Massachusetts General Hospital, Boston; Jeffery L. Kutok, Infinity Pharmaceuticals, Cambridge, MA; Barbara L. Asselin, University of Rochester Medical Center, Rochester; Kara M. Kelly, Columbia University Medical Center, Morgan Stanley
Kristen E Stevenson - Lynda M. Vrooman, Kristen E. Stevenson, Jane O'Brien, Suzanne Dahlberg, Donna S. Neuberg, Stephen E. Sallan, and Lewis B. Silverman, Dana-Farber Cancer Institute; Lynda M. Vrooman, Stephen E. Sallan, and Lewis B. Silverman, Boston Children's Hospital; Jeffrey G. Supko, Massachusetts General Hospital, Boston; Jeffery L. Kutok, Infinity Pharmaceuticals, Cambridge, MA; Barbara L. Asselin, University of Rochester Medical Center, Rochester; Kara M. Kelly, Columbia University Medical Center, Morgan Stanley
Jeffrey G Supko - Lynda M. Vrooman, Kristen E. Stevenson, Jane O'Brien, Suzanne Dahlberg, Donna S. Neuberg, Stephen E. Sallan, and Lewis B. Silverman, Dana-Farber Cancer Institute; Lynda M. Vrooman, Stephen E. Sallan, and Lewis B. Silverman, Boston Children's Hospital; Jeffrey G. Supko, Massachusetts General Hospital, Boston; Jeffery L. Kutok, Infinity Pharmaceuticals, Cambridge, MA; Barbara L. Asselin, University of Rochester Medical Center, Rochester; Kara M. Kelly, Columbia University Medical Center, Morgan Stanley
Jane O'Brien - Lynda M. Vrooman, Kristen E. Stevenson, Jane O'Brien, Suzanne Dahlberg, Donna S. Neuberg, Stephen E. Sallan, and Lewis B. Silverman, Dana-Farber Cancer Institute; Lynda M. Vrooman, Stephen E. Sallan, and Lewis B. Silverman, Boston Children's Hospital; Jeffrey G. Supko, Massachusetts General Hospital, Boston; Jeffery L. Kutok, Infinity Pharmaceuticals, Cambridge, MA; Barbara L. Asselin, University of Rochester Medical Center, Rochester; Kara M. Kelly, Columbia University Medical Center, Morgan Stanley
Suzanne E Dahlberg - Lynda M. Vrooman, Kristen E. Stevenson, Jane O'Brien, Suzanne Dahlberg, Donna S. Neuberg, Stephen E. Sallan, and Lewis B. Silverman, Dana-Farber Cancer Institute; Lynda M. Vrooman, Stephen E. Sallan, and Lewis B. Silverman, Boston Children's Hospital; Jeffrey G. Supko, Massachusetts General Hospital, Boston; Jeffery L. Kutok, Infinity Pharmaceuticals, Cambridge, MA; Barbara L. Asselin, University of Rochester Medical Center, Rochester; Kara M. Kelly, Columbia University Medical Center, Morgan Stanley
Barbara L Asselin - Lynda M. Vrooman, Kristen E. Stevenson, Jane O'Brien, Suzanne Dahlberg, Donna S. Neuberg, Stephen E. Sallan, and Lewis B. Silverman, Dana-Farber Cancer Institute; Lynda M. Vrooman, Stephen E. Sallan, and Lewis B. Silverman, Boston Children's Hospital; Jeffrey G. Supko, Massachusetts General Hospital, Boston; Jeffery L. Kutok, Infinity Pharmaceuticals, Cambridge, MA; Barbara L. Asselin, University of Rochester Medical Center, Rochester; Kara M. Kelly, Columbia University Medical Center, Morgan Stanley
Uma H Athale - Lynda M. Vrooman, Kristen E. Stevenson, Jane O'Brien, Suzanne Dahlberg, Donna S. Neuberg, Stephen E. Sallan, and Lewis B. Silverman, Dana-Farber Cancer Institute; Lynda M. Vrooman, Stephen E. Sallan, and Lewis B. Silverman, Boston Children's Hospital; Jeffrey G. Supko, Massachusetts General Hospital, Boston; Jeffery L. Kutok, Infinity Pharmaceuticals, Cambridge, MA; Barbara L. Asselin, University of Rochester Medical Center, Rochester; Kara M. Kelly, Columbia University Medical Center, Morgan Stanley
Luis A Clavell - Lynda M. Vrooman, Kristen E. Stevenson, Jane O'Brien, Suzanne Dahlberg, Donna S. Neuberg, Stephen E. Sallan, and Lewis B. Silverman, Dana-Farber Cancer Institute; Lynda M. Vrooman, Stephen E. Sallan, and Lewis B. Silverman, Boston Children's Hospital; Jeffrey G. Supko, Massachusetts General Hospital, Boston; Jeffery L. Kutok, Infinity Pharmaceuticals, Cambridge, MA; Barbara L. Asselin, University of Rochester Medical Center, Rochester; Kara M. Kelly, Columbia University Medical Center, Morgan Stanley
Kara M Kelly - Lynda M. Vrooman, Kristen E. Stevenson, Jane O'Brien, Suzanne Dahlberg, Donna S. Neuberg, Stephen E. Sallan, and Lewis B. Silverman, Dana-Farber Cancer Institute; Lynda M. Vrooman, Stephen E. Sallan, and Lewis B. Silverman, Boston Children's Hospital; Jeffrey G. Supko, Massachusetts General Hospital, Boston; Jeffery L. Kutok, Infinity Pharmaceuticals, Cambridge, MA; Barbara L. Asselin, University of Rochester Medical Center, Rochester; Kara M. Kelly, Columbia University Medical Center, Morgan Stanley
Jeffery L Kutok - Lynda M. Vrooman, Kristen E. Stevenson, Jane O'Brien, Suzanne Dahlberg, Donna S. Neuberg, Stephen E. Sallan, and Lewis B. Silverman, Dana-Farber Cancer Institute; Lynda M. Vrooman, Stephen E. Sallan, and Lewis B. Silverman, Boston Children's Hospital; Jeffrey G. Supko, Massachusetts General Hospital, Boston; Jeffery L. Kutok, Infinity Pharmaceuticals, Cambridge, MA; Barbara L. Asselin, University of Rochester Medical Center, Rochester; Kara M. Kelly, Columbia University Medical Center, Morgan Stanley
Caroline Laverdière - Lynda M. Vrooman, Kristen E. Stevenson, Jane O'Brien, Suzanne Dahlberg, Donna S. Neuberg, Stephen E. Sallan, and Lewis B. Silverman, Dana-Farber Cancer Institute; Lynda M. Vrooman, Stephen E. Sallan, and Lewis B. Silverman, Boston Children's Hospital; Jeffrey G. Supko, Massachusetts General Hospital, Boston; Jeffery L. Kutok, Infinity Pharmaceuticals, Cambridge, MA; Barbara L. Asselin, University of Rochester Medical Center, Rochester; Kara M. Kelly, Columbia University Medical Center, Morgan Stanley
Steven E Lipshultz - Lynda M. Vrooman, Kristen E. Stevenson, Jane O'Brien, Suzanne Dahlberg, Donna S. Neuberg, Stephen E. Sallan, and Lewis B. Silverman, Dana-Farber Cancer Institute; Lynda M. Vrooman, Stephen E. Sallan, and Lewis B. Silverman, Boston Children's Hospital; Jeffrey G. Supko, Massachusetts General Hospital, Boston; Jeffery L. Kutok, Infinity Pharmaceuticals, Cambridge, MA; Barbara L. Asselin, University of Rochester Medical Center, Rochester; Kara M. Kelly, Columbia University Medical Center, Morgan Stanley
Bruno Michon - Lynda M. Vrooman, Kristen E. Stevenson, Jane O'Brien, Suzanne Dahlberg, Donna S. Neuberg, Stephen E. Sallan, and Lewis B. Silverman, Dana-Farber Cancer Institute; Lynda M. Vrooman, Stephen E. Sallan, and Lewis B. Silverman, Boston Children's Hospital; Jeffrey G. Supko, Massachusetts General Hospital, Boston; Jeffery L. Kutok, Infinity Pharmaceuticals, Cambridge, MA; Barbara L. Asselin, University of Rochester Medical Center, Rochester; Kara M. Kelly, Columbia University Medical Center, Morgan Stanley
Marshall Schorin - Lynda M. Vrooman, Kristen E. Stevenson, Jane O'Brien, Suzanne Dahlberg, Donna S. Neuberg, Stephen E. Sallan, and Lewis B. Silverman, Dana-Farber Cancer Institute; Lynda M. Vrooman, Stephen E. Sallan, and Lewis B. Silverman, Boston Children's Hospital; Jeffrey G. Supko, Massachusetts General Hospital, Boston; Jeffery L. Kutok, Infinity Pharmaceuticals, Cambridge, MA; Barbara L. Asselin, University of Rochester Medical Center, Rochester; Kara M. Kelly, Columbia University Medical Center, Morgan Stanley
Mary V Relling - Lynda M. Vrooman, Kristen E. Stevenson, Jane O'Brien, Suzanne Dahlberg, Donna S. Neuberg, Stephen E. Sallan, and Lewis B. Silverman, Dana-Farber Cancer Institute; Lynda M. Vrooman, Stephen E. Sallan, and Lewis B. Silverman, Boston Children's Hospital; Jeffrey G. Supko, Massachusetts General Hospital, Boston; Jeffery L. Kutok, Infinity Pharmaceuticals, Cambridge, MA; Barbara L. Asselin, University of Rochester Medical Center, Rochester; Kara M. Kelly, Columbia University Medical Center, Morgan Stanley
Harvey J Cohen - Lynda M. Vrooman, Kristen E. Stevenson, Jane O'Brien, Suzanne Dahlberg, Donna S. Neuberg, Stephen E. Sallan, and Lewis B. Silverman, Dana-Farber Cancer Institute; Lynda M. Vrooman, Stephen E. Sallan, and Lewis B. Silverman, Boston Children's Hospital; Jeffrey G. Supko, Massachusetts General Hospital, Boston; Jeffery L. Kutok, Infinity Pharmaceuticals, Cambridge, MA; Barbara L. Asselin, University of Rochester Medical Center, Rochester; Kara M. Kelly, Columbia University Medical Center, Morgan Stanley
Donna S Neuberg - Lynda M. Vrooman, Kristen E. Stevenson, Jane O'Brien, Suzanne Dahlberg, Donna S. Neuberg, Stephen E. Sallan, and Lewis B. Silverman, Dana-Farber Cancer Institute; Lynda M. Vrooman, Stephen E. Sallan, and Lewis B. Silverman, Boston Children's Hospital; Jeffrey G. Supko, Massachusetts General Hospital, Boston; Jeffery L. Kutok, Infinity Pharmaceuticals, Cambridge, MA; Barbara L. Asselin, University of Rochester Medical Center, Rochester; Kara M. Kelly, Columbia University Medical Center, Morgan Stanley
Stephen E Sallan - Lynda M. Vrooman, Kristen E. Stevenson, Jane O'Brien, Suzanne Dahlberg, Donna S. Neuberg, Stephen E. Sallan, and Lewis B. Silverman, Dana-Farber Cancer Institute; Lynda M. Vrooman, Stephen E. Sallan, and Lewis B. Silverman, Boston Children's Hospital; Jeffrey G. Supko, Massachusetts General Hospital, Boston; Jeffery L. Kutok, Infinity Pharmaceuticals, Cambridge, MA; Barbara L. Asselin, University of Rochester Medical Center, Rochester; Kara M. Kelly, Columbia University Medical Center, Morgan Stanley
Lewis B Silverman - Lynda M. Vrooman, Kristen E. Stevenson, Jane O'Brien, Suzanne Dahlberg, Donna S. Neuberg, Stephen E. Sallan, and Lewis B. Silverman, Dana-Farber Cancer Institute; Lynda M. Vrooman, Stephen E. Sallan, and Lewis B. Silverman, Boston Children's Hospital; Jeffrey G. Supko, Massachusetts General Hospital, Boston; Jeffery L. Kutok, Infinity Pharmaceuticals, Cambridge, MA; Barbara L. Asselin, University of Rochester Medical Center, Rochester; Kara M. Kelly, Columbia University Medical Center, Morgan Stanley
Publication Details: Journal of clinical oncology, Vol.31(9), pp.1202-1210
Academic Unit: UMMG Department of Pediatrics
Language: English
Resource Type: Journal article
PMID: 23358966
PMCID: PMC3595424
Record Identifier: 991031575680602976