title: Erwinia asparaginase achieves therapeutic activity after pegaspargase allergy: a report from the Children's Oncology Group.
abstract: AALL07P2 evaluated whether substitution of Erwinia asparaginase 25000 IU/m(2) for 6 doses given intramuscularly Monday/Wednesday/Friday (M/W/F) to children and young adults with acute lymphoblastic leukemia and clinical allergy to pegaspargase would provide a 48-hour nadir serum asparaginase activity (NSAA) ≥ 0.10 IU/mL. AALL07P2 enrolled 55 eligible/evaluable patients. NSAA ≥ 0.1 IU/mL was achieved in 38 of 41 patients (92.7%) with acceptable samples 48 hours and in 38 of 43 patients (88.4%) 72 hours after dosing during course 1. Among samples obtained during all courses, 95.8% (252 of 263) of 48-hour samples and 84.5% (125 of 148) of 72-hour samples had NSAA ≥ 0.10-IU/mL. Pharmacokinetic parameters were estimated by fitting the serum asparaginase activity-time course for all 6 doses given during course 1 to a 1-compartment open model with first order absorption. Erwinia asparaginase administered with this schedule achieved therapeutic NSAA at both 48 and 72 hours and was well tolerated with no reports of hemorrhage, thrombosis, or death, and few cases of grade 2 to 3 allergic reaction (n = 6), grade 1 to 3 hyperglycemia (n = 6), or grade 1 pancreatitis (n = 1). Following allergy to pegaspargase, Erwinia asparaginase 25000 IU/m(2) × 6 intramuscularly M/W/F can be substituted for a single dose of pegaspargase.
authors.affiliation: US Army Medical Research and Materiel Command, Fort Detrick, MD 21702-5012, USA. wanda.l.salzer.mil@mail.mil
authors.forename: Wanda L
authors.initials: WL
authors.lastname: Salzer
authors.forename: Barbara
authors.initials: B
authors.lastname: Asselin
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Supko
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Devidas
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Kaiser
authors.forename: Paul
authors.initials: P
authors.lastname: Plourde
authors.forename: Naomi J
authors.initials: NJ
authors.lastname: Winick
authors.forename: Gregory H
authors.initials: GH
authors.lastname: Reaman
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Raetz
authors.forename: William L
authors.initials: WL
authors.lastname: Carroll
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Hunger
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004342:Drug Hypersensitivity / Q000209:etiology; D057915:Drug Substitution; D004885:Erwinia / Q000201:enzymology*; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008495:Medical Oncology / Q000379:methods / Q000458:organization & administration; D011092:Polyethylene Glycols / Q000009:adverse effects*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D012074:Remission Induction / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; C042705:pegaspargase; D001215:Asparaginase