title: Silent hypersensitivity to Escherichia coli asparaginase in children with acute lymphoblastic leukemia.
abstract: This prospective study aimed to assess the incidence of silent hypersensitivity to Escherichia coli asparaginase in the treatment of acute lymphoblastic leukemia (ALL). Thirty-three children with newly diagnosed ALL were included in the study and treated according to the FRALLE 2000 protocol. The 'A group' (n = 18) differed from the 'B-T group' (n = 15) by a less intensive chemotherapy, the absence of concurrent prednisone therapy, and different asparaginase administration modalities during the second intensification. Asparagine, asparaginase activity, and anti-asparaginase antibodies were measured in each phase before the next injection of asparaginase. Eighteen percent of children presented a silent hypersensitivity. Most of them were in the 'B-T group' (p = 0.07), and maintained low antibody titers throughout the treatment. Clinical hypersensitivity was statistically more frequent in group A (p = 0.002), and allergy occurred mainly during the second intensification when antibody concentrations were significantly increased. We did not find any significant difference between asparaginase activity or asparagine depletion between the silent hypersensitivity and clinical allergy groups. In all, the results of this study suggest that chemotherapy and corticosteroid therapy associated with asparaginase treatment can lower antibody production and contribute to maintaining a silent hypersensitivity state.
authors.affiliation: Service d'Onco-Hématologie Pédiatrique, CHU de Nantes, Hopital Mère-Enfant, Nantes, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Strullu
authors.forename: Nadège
authors.initials: N
authors.lastname: Corradini
authors.forename: Marie
authors.initials: M
authors.lastname: Audrain
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Orsonneau
authors.forename: Daniel
authors.initials: D
authors.lastname: Bouige
authors.forename: Patrick
authors.initials: P
authors.lastname: Thomare
authors.forename: Claudine
authors.initials: C
authors.lastname: Vermot-Desroches
authors.forename: Adeline
authors.initials: A
authors.lastname: Mansuy
authors.forename: Arnaud
authors.initials: A
authors.lastname: Legrand
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Rozé
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.forename: Françoise
authors.initials: F
authors.lastname: Méchinaud
mesh_terms: D000293:Adolescent; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001215:Asparaginase / Q000009:adverse effects* / Q000276:immunology; D001216:Asparagine / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004342:Drug Hypersensitivity; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000201:enzymology*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000970:Antineoplastic Agents; D001216:Asparagine; D001215:Asparaginase