title: Development of asparaginase Erwinia chrysanthemi for the treatment of acute lymphoblastic leukemia.
abstract: Since it was identified in 1963 as the antileukemic agent in guinea pig serum, L-asparaginase (ASNase) has become an integral component of chemotherapy protocols to treat patients with acute lymphoblastic leukemia (ALL). Escherichia coli and Erwinia chrysanthemi provide the sources of ASNase used clinically today. From the time ASNase was first introduced into treatment protocols, the 5-year survival rate has increased significantly, particularly in children and adolescents. E. coli-derived ASNase was approved in 1978 to be used as part of a multiagent chemotherapy to treat ALL. However, the development of hypersensitivity in 10-30% of patients often leads to treatment discontinuation. E. chrysanthemi-derived ASNase (referred to herein as ASNase Erwinia chrysanthemi) is immunologically distinct from E. coli ASNase and therefore does not cross-react with the E. coli enzyme. In 2011, ASNase Erwinia chrysanthemi was approved in the United States for patients who develop hypersensitivity to E. coli-derived ASNase. When indicated, a switch from ASNase E. coli to ASNase E. chrysanthemi allows patients to continue to receive treatment and maintain therapeutic levels of ASNase activity. Therapeutic drug monitoring may help ensure that therapeutic enzyme levels are maintained. Pegylated recombinant ASNase Erwinia chrysanthemi is currently being developed to improve pharmacokinetic properties and reduce immunogenicity.
authors.affiliation: United States Army Medical Research and Materiel Command, Fort Detrick, Maryland.
authors.forename: Wanda L
authors.initials: WL
authors.lastname: Salzer
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Asselin
authors.forename: Paul V
authors.initials: PV
authors.lastname: Plourde
authors.forename: Tim
authors.initials: T
authors.lastname: Corn
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Hunger
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000627:therapeutic use*; D001215:Asparaginase / Q000302:isolation & purification / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000639:trends; D003429:Cross Reactions / Q000187:drug effects / Q000276:immunology; D016974:Dickeya chrysanthemi / Q000201:enzymology*; D055808:Drug Discovery / Q000639:trends*; D006168:Guinea Pigs; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001215:Asparaginase
keywords: Erwinia chrysanthemi; asparaginase; hypersensitivity; leukemia