title: Anti-Escherichia coli asparaginase antibody levels determine the activity of second-line treatment with pegylated E coli asparaginase: a retrospective analysis within the ALL-BFM trials.
abstract: Hypersensitivity reactions limit the use of the antileukemic enzyme asparaginase (ASE). We evaluated Ab levels against Escherichia coli ASE and ASE activity in 1221 serum samples from 329 patients with acute lymphoblastic leukemia who had received ASE treatment according to the ALL-BFM 2000 or the ALL-REZ BFM 2002 protocol for primary or relapsed disease. ASE activity during first-line treatment with native E coli ASE and second-line treatment with pegylated E coli ASE was inversely related to anti-E coli ASE Ab levels (P < .0001; Spearman rank order correlation). An effect on ASE activity during second-line treatment with pegylated E coli ASE was, however, only observed when anti-E coli ASE Ab levels were high (> 200 AU/mL). In the presence of moderate or intermediate Ab levels (6.25-200 AU/mL) the switch from native to pegylated E coli ASE resulted in a significant increase of ASE activity above the threshold of 100 U/L (P < .05). Erwinia chrysanthemi ASE activity was not correlated with anti-E coli ASE Ab levels. Erwinia ASE was found to be the best ASE alternative if Ab levels against E coli ASE exceed 200 AU/mL. This retrospective analysis is the first to describe the relationship between the level of anti-E coli ASE Abs and serum activity of pegylated E coli ASE used second-line after native E coli ASE.
authors.affiliation: Department of Pediatric Hematology and Oncology, University Children's Hospital of Muenster, Muenster, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Willer
authors.forename: Joachim
authors.initials: J
authors.lastname: Gerss
authors.forename: Thorsten
authors.initials: T
authors.lastname: König
authors.forename: Dieter
authors.initials: D
authors.lastname: Franke
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Kühnel
authors.forename: Günter
authors.initials: G
authors.lastname: Henze
authors.forename: Arendt
authors.initials: A
authors.lastname: von Stackelberg
authors.forename: Anja
authors.initials: A
authors.lastname: Möricke
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
authors.forename: Joachim
authors.initials: J
authors.lastname: Boos
authors.forename: Claudia
authors.initials: C
authors.lastname: Lanvers-Kaminsky
mesh_terms: D000293:Adolescent; D000328:Adult; D000906:Antibodies / Q000097:blood*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000276:immunology / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage* / Q000276:immunology* / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological / Q000097:blood; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D003630:Daunorubicin / Q000276:immunology / Q000627:therapeutic use; D004342:Drug Hypersensitivity / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D016903:Drug Monitoring / Q000379:methods; D004926:Escherichia coli / Q000201:enzymology / Q000276:immunology; D029968:Escherichia coli Proteins / Q000276:immunology*; D006801:Humans; D007223:Infant; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000188:drug therapy*; D011241:Prednisone / Q000276:immunology / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D012189:Retrospective Studies; D014750:Vincristine / Q000276:immunology / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D054316:Biomarkers, Pharmacological; D029968:Escherichia coli Proteins; D011994:Recombinant Proteins; D014750:Vincristine; D001215:Asparaginase; D011241:Prednisone; D003630:Daunorubicin