title: Activity and Toxicity of Intravenous Erwinia Asparaginase Following Allergy to E. coli-Derived Asparaginase in Children and Adolescents With Acute Lymphoblastic Leukemia.
abstract: BACKGROUND
  Erwinia asparaginase is antigenically distinct from E.coli-derived asparaginase and may be used after E.coli-derived asparaginase hypersensitivity. In a single-arm, multicenter study, we evaluated nadir serum asparaginase activity (NSAA) and toxicity with intravenously administered asparaginase Erwinia chrysanthemi (IV-Erwinia) in children and adolescents with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma with hypersensitivity to E.coli-derived asparaginase.
  
  
  METHODS
  Between 2012 and 2013, 30 patients (age 1-17 years) enrolled from 10 centers. Patients received IV-Erwinia, 25,000 IU/m(2)/dose on Monday/Wednesday/Friday, for 2 consecutive-weeks (6 doses = 1 cycle) for each dose of pegaspargase remaining in the original treatment plan. The primary objective was to determine the proportion of patients achieving NSAA ≥ 0.1 IU/ml 48 hr after dose 5 in Cycle 1. Secondary objectives included determining the proportion achieving NSAA ≥ 0.1 IU/ml 72 hr after Cycle 1 dose 6, and the frequency of asparaginase-related toxicities.
  
  
  RESULTS
  Twenty-six patients completed Cycle 1; 24 were evaluable for NSAA assessment. In Cycle 1, NSAA ≥ 0.10 IU/ml was detected in 83% of patients (95% confidence interval [CI], 63-95%) 48 hr post-dose 5 (mean ± SD; 0.32 IU/ml ± 0.23), and in 43% (95% CI, 22-66%) 72 hr post-dose 6 (mean ± SD; 0.089 IU/ml ± 0.072). For all 30 patients over all cycles, hypersensitivity/infusional reactions with IV-Erwinia occurred in 37%, pancreatitis 7%, and thrombosis 3%.
  
  
  CONCLUSIONS
  IV-Erwinia administration in children/adolescents appeared feasible and tolerable. A therapeutically-effective NSAA (≥ 0.10 IU/ml) was achieved in most patients at 48 hr, but in fewer than half 72 hr post-dosing, suggesting that monitoring NSAA levels and/or every 48 hr dosing may be indicated.
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Division of Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Lynda M
authors.initials: LM
authors.lastname: Vrooman
authors.affiliation: Division of Oncology, Children's Hospital of Orange County, Orange, California.
authors.forename: Ivan I
authors.initials: II
authors.lastname: Kirov
authors.affiliation: Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas.
authors.forename: ZoAnn E
authors.initials: ZE
authors.lastname: Dreyer
authors.affiliation: Division of Pediatric Hematology, Oncology, and Bone Marrow Transplant, Children's Hospital of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Michael
authors.initials: M
authors.lastname: Kelly
authors.affiliation: Ann & Robert H. Lurie Children's Hospital and Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors.forename: Nobuko
authors.initials: N
authors.lastname: Hijiya
authors.affiliation: Pediatric Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Brown
authors.affiliation: Department of Pediatric Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Drachtman
authors.affiliation: Pediatric Hematology-Oncology, Children's Hospitals & Clinics of Minnesota, Minneapolis, Minnesota.
authors.forename: Yoav H
authors.initials: YH
authors.lastname: Messinger
authors.affiliation: Division of Hematology/Oncology, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: A Kim
authors.initials: AK
authors.lastname: Ritchey
authors.affiliation: Department of Hematology-Oncology, All Children's Hospital, St. Petersburg, Florida.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Hale
authors.affiliation: Center for Cancer & Blood Disorders, Children's Hospital Colorado, Aurora, Colorado.
authors.forename: Kelly
authors.initials: K
authors.lastname: Maloney
authors.affiliation: Jazz Pharmaceuticals, Palo Alto, California.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Formerly of Jazz Pharmaceuticals, Palo Alto, California.
authors.forename: Paul V
authors.initials: PV
authors.lastname: Plourde
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Division of Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Lewis B
authors.initials: LB
authors.lastname: Silverman
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001215:Asparaginase / Q000097:blood* / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D016974:Dickeya chrysanthemi / Q000201:enzymology*; D004342:Drug Hypersensitivity; D004926:Escherichia coli; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D001215:Asparaginase
keywords: Erwinia asparaginase; acute lymphoblastic leukemia; childhood ALL; clinical trials; pharmacokinetics