title: Safety profile of asparaginase Erwinia chrysanthemi in a large compassionate-use trial.
abstract: BACKGROUND
  L-Asparaginase is an integral component of standard chemotherapy regimens for the treatment of acute lymphoblastic leukemia (ALL). Clinical hypersensitivity, a common reason for treatment discontinuation, has been reported in 10-30% of patients receiving Escherichia coli-derived asparaginase. After hypersensitivity, E. coli-derived asparaginase should be discontinued and an alternative asparaginase preparation, such as asparaginase Erwinia chrysanthemi, may be initiated. We conducted a compassionate-use study to collect additional safety information on asparaginase Erwinia chrysanthemi and to support FDA approval of the product.
  
  
  METHODS
  Patients with ALL or lymphoblastic lymphoma (LBL; N = 1368) who developed a hypersensitivity reaction (grade ≥2) to an E. coli-derived asparaginase participated in this trial. The recommended asparaginase Erwinia chrysanthemi dose was 25,000 IU/m(2) three days per week (Monday/Wednesday/Friday) for two consecutive weeks for each missed pegylated E. coli-derived asparaginase dose and 25,000 IU/m(2) for each missed nonpegylated asparaginase dose for the completion of their planned asparaginase treatment.
  
  
  RESULTS
  Adverse event reports and/or case report forms were completed for 940 patients. The most common adverse event (AE) was hypersensitivity (13.6%). Eighteen patients (1.9%) died during the study. Most patients (77.6%) completed their planned asparaginase treatment with asparaginase Erwinia chrysanthemi. There was no apparent difference in the incidence of the most commonly reported AEs with asparaginase treatment by age, administration, or disease state.
  
  
  CONCLUSIONS
  This study further established the safety profile of asparaginase Erwinia chrysanthemi in patients with ALL or LBL who had a hypersensitivity reaction to an E. coli-derived asparaginase.
authors.affiliation: Jazz Pharmaceuticals, Inc., Palo Alto, California.
authors.forename: Paul V
authors.initials: PV
authors.lastname: Plourde
authors.forename: Sima
authors.initials: S
authors.lastname: Jeha
authors.forename: Nobuko
authors.initials: N
authors.lastname: Hijiya
authors.forename: Frank G
authors.initials: FG
authors.lastname: Keller
authors.forename: Lewis B
authors.initials: LB
authors.lastname: Silverman
authors.forename: Susan R
authors.initials: SR
authors.lastname: Rheingold
authors.forename: ZoAnn E
authors.initials: ZE
authors.lastname: Dreyer
authors.forename: Gary V
authors.initials: GV
authors.lastname: Dahl
authors.forename: Taheri
authors.initials: T
authors.lastname: Mercedes
authors.forename: Chinglin
authors.initials: C
authors.lastname: Lai
authors.forename: Tim
authors.initials: T
authors.lastname: Corn
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001215:Asparaginase / Q000008:administration & dosage* / Q000009:adverse effects; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D016974:Dickeya chrysanthemi / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004342:Drug Hypersensitivity / Q000209:etiology / Q000401:mortality; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality; D011994:Recombinant Proteins / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D011994:Recombinant Proteins; D001215:Asparaginase
keywords: ALL; Escherichia coli-derived asparaginase; acute lymphoblastic leukemia; asparaginase Erwinia chrysanthemi; hypersensitivity; lymphoblastic lymphoma; safety