title: Consensus expert recommendations for identification and management of asparaginase hypersensitivity and silent inactivation.
abstract: L-asparaginase is an integral component of therapy for acute lymphoblastic leukemia. However, asparaginase-related complications, including the development of hypersensitivity reactions, can limit its use in individual patients. Of considerable concern in the setting of clinical allergy is the development of neutralizing antibodies and associated asparaginase inactivity. Also problematic in the use of asparaginase is the potential for the development of silent inactivation, with the formation of neutralizing antibodies and reduced asparaginase activity in the absence of a clinically evident allergic reaction. Here we present guidelines for the identification and management of clinical hypersensitivity and silent inactivation with Escherichia coli- and Erwinia chrysanthemi- derived asparaginase preparations. These guidelines were developed by a consensus panel of experts following a review of the available published data. We provide a consensus of expert opinions on the role of serum asparaginase level assessment, indications for switching asparaginase preparation, and monitoring after change in asparaginase preparation.
authors.affiliation: Department of Pediatric Hematology/Oncology, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands i.vandersluis@erasmusmc.nl lynda_vrooman@dfci.harvard.edu.
authors.forename: Inge M
authors.initials: IM
authors.lastname: van der Sluis
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Division of Hematology/Oncology, Boston Children's Hospital, MA, USA i.vandersluis@erasmusmc.nl lynda_vrooman@dfci.harvard.edu.
authors.forename: Lynda M
authors.initials: LM
authors.lastname: Vrooman
authors.affiliation: Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
authors.affiliation: Department of Pediatric Hematology, Hôpital Robert Debré, Paris and University Paris Diderot, France.
authors.forename: Andre
authors.initials: A
authors.lastname: Baruchel
authors.affiliation: University Medical Centre Hamburg-Eppendorf, Clinic of Paediatric Hematology and Oncology, Hamburg, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Escherich
authors.affiliation: Great Ormond Street Hospital, London, UK.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Goulden
authors.affiliation: Pediatric Hematology/Oncology and Stem cell transplantation, Ghent University Hospital, Belgium.
authors.forename: Veerle
authors.initials: V
authors.lastname: Mondelaers
authors.affiliation: Department of Pediatric Hematology/Oncology, University Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Sanchez de Toledo
authors.affiliation: Pediatric Hematology-Oncology Unit, Department of Pediatrics, University of Milano-Bicocca, Hospital S. Gerardo, Monza.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Rizzari
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Division of Hematology/Oncology, Boston Children's Hospital, MA, USA.
authors.forename: Lewis B
authors.initials: LB
authors.lastname: Silverman
authors.affiliation: Division of Haematology/Oncology, The Hospital for Sick Children and Department of Paediatrics, University of Toronto, Ontario, Canada.
authors.forename: James A
authors.initials: JA
authors.lastname: Whitlock
mesh_terms: D057134:Antibodies, Neutralizing / Q000096:biosynthesis / Q000097:blood; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001215:Asparaginase / Q000037:antagonists & inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016974:Dickeya chrysanthemi / Q000235:genetics / Q000378:metabolism; D019468:Disease Management; D004342:Drug Hypersensitivity / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D016903:Drug Monitoring; D057915:Drug Substitution; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D011994:Recombinant Proteins / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D057134:Antibodies, Neutralizing; D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D001215:Asparaginase