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/m(2) fixed dose (FD) or individualized dose (ID) starting at 12,500-IU/m(2), 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.
RCT Entities:
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/m(2) fixed dose (FD) or individualized dose (ID) starting at 12,500-IU/m(2), 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.
Authors: L B Silverman; R D Gelber; V K Dalton; B L Asselin; R D Barr; L A Clavell; C A Hurwitz; A Moghrabi; Y Samson; M A Schorin; S Arkin; L Declerck; H J Cohen; S E Sallan Journal: Blood Date: 2001-03-01 Impact factor: 22.113
Authors: Vassilios I Avramis; Susan Sencer; Antonia P Periclou; Harland Sather; Bruce C Bostrom; Lewis J Cohen; Alice G Ettinger; Lawrence J Ettinger; Janet Franklin; Paul S Gaynon; Joanne M Hilden; Beverly Lange; Fataneh Majlessipour; Pracad Mathew; Michael Needle; Joseph Neglia; Gregory Reaman; John S Holcenberg; Linda Stork Journal: Blood Date: 2002-03-15 Impact factor: 22.113
Authors: C Rizzari; M Zucchetti; V Conter; L Diomede; A Bruno; L Gavazzi; M Paganini; P Sparano; L Lo Nigro; M Aricò; M Milani; M D'Incalci Journal: Ann Oncol Date: 2000-02 Impact factor: 32.976
Authors: Britta Bürger; Rita Beier; Martin Zimmermann; Jörn D Beck; Alfred Reiter; Martin Schrappe Journal: Pediatr Blood Cancer Date: 2005-03 Impact factor: 3.167
Authors: Bruce C Bostrom; Martha R Sensel; Harland N Sather; Paul S Gaynon; Mei K La; Katherine Johnston; Gary R Erdmann; Stuart Gold; Nyla A Heerema; Raymond J Hutchinson; Arthur J Provisor; Michael E Trigg Journal: Blood Date: 2003-01-16 Impact factor: 22.113
Authors: Asim F Belgaumi; Mohammed Al-Bakrah; Mohammed Al-Mahr; Abdullah Al-Jefri; AbdulRahman Al-Musa; Mahasen Saleh; Mohammed F Salim; Mohammed Osman; Layla Osman; Hassan El-Solh Journal: Cancer Date: 2003-06-01 Impact factor: 6.860
Authors: Wing H Tong; Rob Pieters; Hester A de Groot-Kruseman; Wim C J Hop; Joachim Boos; Wim J E Tissing; Inge M van der Sluis Journal: Haematologica Date: 2014-08-22 Impact factor: 9.941
Authors: Emily S Tonorezos; Melissa M Hudson; Angela B Edgar; Leontien C Kremer; Charles A Sklar; W Hamish B Wallace; Kevin C Oeffinger Journal: Lancet Diabetes Endocrinol Date: 2015-04-12 Impact factor: 32.069
Authors: Troy Z Horvat; Joshua J Pecoraro; Ryan J Daley; Larry W Buie; Amber C King; Raajit K Rampal; Martin S Tallman; Jae H Park; Dan Douer Journal: Leuk Res Date: 2016-08-26 Impact factor: 3.156
Authors: Laura J Janke; Sara L Van Driest; Mary V Portera; Ravi V Atreya; Joshua C Denny; Deqing Pei; Cheng Cheng; Sue C Kaste; Hiroto Inaba; Sima Jeha; Ching-Hon Pui; Mary V Relling; Seth E Karol Journal: Blood Date: 2019-08-13 Impact factor: 22.113
Authors: Wanda L Salzer; Michael J Burke; Meenakshi Devidas; Si Chen; Lia Gore; Eric C Larsen; Michael Borowitz; Brent Wood; Nyla A Heerema; Andrew J Carroll; Joanne M Hilden; Mignon L Loh; Elizabeth A Raetz; Naomi J Winick; William L Carroll; Stephen P Hunger Journal: Cancer Date: 2017-12-19 Impact factor: 6.860