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 language | English |
|---|---|
| Pages (from-to) | 1202-1210 |
| Number of pages | 9 |
| Journal | Journal of Clinical Oncology |
| Volume | 31 |
| Issue number | 9 |
| DOIs | |
| State | Published - Mar 20 2013 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
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 journal › Article
}
TY - JOUR
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.
UR - http://www.scopus.com/inward/record.url?scp=84875246943&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84875246943&partnerID=8YFLogxK
U2 - 10.1200/JCO.2012.43.2070
DO - 10.1200/JCO.2012.43.2070
M3 - Article
C2 - 23358966
AN - SCOPUS:84875246943
VL - 31
SP - 1202
EP - 1210
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
SN - 0732-183X
IS - 9
ER -