title: Five-year single-center study of asparaginase therapy within the ALL-BFM 2000 trial.
abstract: BACKGROUND
  Therapeutic drug monitoring (TDM) of asparaginase (ASNase), a fundamental element of acute lymphoblastic leukemia treatment, was integrated in the ALL-BFM 2000 protocol on a voluntary basis.
  
  
  METHODS
  Over a 5-year period, 127 patients (1,355 samples) were monitored for asparaginase activity in a single-center setting. We report monitoring data from throughout the ASNase containing treatment elements. Additional information obtained on risk stratification, minimal residual disease (MRD), steroid randomization and relapse is discussed in relation to ASNase activity.
  
  
  RESULTS
  At completion of the induction phase 93% (115/124) of patients showed sufficient ASNase activity (5,000 U/m(2) Escherichia coli ASNase), 77 of 86 (90%) monitored patients finished the first re-intensification element without requiring Erwinia ASNase. MRD, risk stratification and steroid randomization were not associated with significant differences in ASNase activity. Of patients who relapsed, only 25% (3/12) were able to maintain sufficient ASNase activity after E. coli ASNase.
  
  
  CONCLUSIONS
  This single-center data set gives a true and unbiased insight into clinical reality of ASNase therapy. It shows no significant relationship between MRD positivity or risk stratification and ASNase treatment intensity. Overall, within the ALL-BFM 2000 trial, 90% of patients completed first re-intensification without requiring third-line Erwinia ASNase.
authors.affiliation: Department of Paediatric Haematology and Oncology, University Hospital Muenster, Muenster, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Schrey
authors.forename: Katharina
authors.initials: K
authors.lastname: Speitel
authors.forename: Claudia
authors.initials: C
authors.lastname: Lanvers-Kaminsky
authors.forename: Joachim
authors.initials: J
authors.lastname: Gerss
authors.forename: Anja
authors.initials: A
authors.lastname: Möricke
authors.forename: Joachim
authors.initials: J
authors.lastname: Boos
mesh_terms: D000293:Adolescent; D001215:Asparaginase / Q000008:administration & dosage* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D018365:Neoplasm, Residual / Q000188:drug therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012008:Recurrence; D018570:Risk Assessment; D013256:Steroids / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D013256:Steroids; D001215:Asparaginase