title: Intravenous PEG-asparaginase during remission induction in children and adolescents with newly diagnosed acute lymphoblastic leukemia.
abstract: Over the past several decades, L-asparaginase, an important component of therapy for acute lymphoblastic leukemia (ALL), has typically been administered intramuscularly rather than intravenously in North America because of concerns regarding anaphylaxis. We evaluated the feasibility of giving polyethylene glycosylated (PEG)-asparaginase, the polyethylene glycol conjugate of Escherichia coli L-asparaginase, by intravenous infusion in children with ALL. Between 2005 and 2007, 197 patients (age, 1-17 years) were enrolled on Dana-Farber Cancer Institute ALL Consortium Protocol 05-01 and received a single dose of intravenous PEG-asparaginase (2500 IU/m(2)) over 1 hour during remission induction. Serum asparaginase activity more than 0.1 IU/mL was detected in 95%, 88%, and 7% of patients at 11, 18, and 25 days after dosing, respectively. Toxicities included allergy (1.5%), venous thrombosis (2%), and pancreatitis (4.6%). We conclude that intravenous administration of PEG-asparaginase is tolerable in children with ALL, and potentially therapeutic enzyme activity is maintained for at least 2 weeks after a single dose in most patients. This trial was registered at www.clinicaltrials.gov as #NCT00400946.
authors.affiliation: Departments of Pediatric Oncology, Biostatistics, and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Lewis_Silverman@dfci.harvard.edu
authors.forename: Lewis B
authors.initials: LB
authors.lastname: Silverman
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Supko
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Stevenson
authors.forename: Christina
authors.initials: C
authors.lastname: Woodward
authors.forename: Lynda M
authors.initials: LM
authors.lastname: Vrooman
authors.forename: Donna S
authors.initials: DS
authors.lastname: Neuberg
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Asselin
authors.forename: Uma H
authors.initials: UH
authors.lastname: Athale
authors.forename: Luis
authors.initials: L
authors.lastname: Clavell
authors.forename: Peter D
authors.initials: PD
authors.lastname: Cole
authors.forename: Kara M
authors.initials: KM
authors.lastname: Kelly
authors.forename: Caroline
authors.initials: C
authors.lastname: Laverdière
authors.forename: Bruno
authors.initials: B
authors.lastname: Michon
authors.forename: Marshall
authors.initials: M
authors.lastname: Schorin
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Schwartz
authors.forename: Jane E
authors.initials: JE
authors.lastname: O'Brien
authors.forename: Harvey J
authors.initials: HJ
authors.lastname: Cohen
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Sallan
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001215:Asparaginase / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D002648:Child; D002675:Child, Preschool; D005240:Feasibility Studies; D006801:Humans; D007223:Infant; D007262:Infusions, Intravenous; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy*; D012074:Remission Induction
chemical_list: D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; C042705:pegaspargase; D001215:Asparaginase