title: L-asparaginase treatment in acute lymphoblastic leukemia: a focus on Erwinia asparaginase.
abstract: Asparaginases are a cornerstone of treatment protocols for acute lymphoblastic leukemia (ALL) and are used for remission induction and intensification treatment in all pediatric regimens and in the majority of adult treatment protocols. Extensive clinical data have shown that intensive asparaginase treatment improves clinical outcomes in childhood ALL. Three asparaginase preparations are available: the native asparaginase derived from Escherichia coli (E. coli asparaginase), a pegylated form of this enzyme (PEG-asparaginase), and a product isolated from Erwinia chrysanthemi, ie, Erwinia asparaginase. Clinical hypersensitivity reactions and silent inactivation due to antibodies against E. coli asparaginase, lead to inactivation of E. coli asparaginase in up to 60% of cases. Current treatment protocols include E. coli asparaginase or PEG-asparaginase for first-line treatment of ALL. Typically, patients exhibiting sensitivity to one formulation of asparaginase are switched to another to ensure they receive the most efficacious treatment regimen possible. Erwinia asparaginase is used as a second- or third-line treatment in European and US protocols. Despite the universal inclusion of asparaginase in such treatment protocols, debate on the optimal formulation and dosage of these agents continues. This article provides an overview of available evidence for optimal use of Erwinia asparaginase in the treatment of ALL.
authors.affiliation: Erasmus MC-Sophia Children's Hospital, Rotterdam, Netherlands. rob.pieters@erasmusmc.nl
authors.forename: Rob
authors.initials: R
authors.lastname: Pieters
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Hunger
authors.forename: Joachim
authors.initials: J
authors.lastname: Boos
authors.forename: Carmelo
authors.initials: C
authors.lastname: Rizzari
authors.forename: Lewis
authors.initials: L
authors.lastname: Silverman
authors.forename: Andre
authors.initials: A
authors.lastname: Baruchel
authors.forename: Nicola
authors.initials: N
authors.lastname: Goekbuget
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
mesh_terms: D001215:Asparaginase / Q000009:adverse effects / Q000627:therapeutic use*; D004338:Drug Combinations; D004342:Drug Hypersensitivity; D016903:Drug Monitoring; D004885:Erwinia / Q000201:enzymology*; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D013148:Spironolactone; D013449:Sulfonamides
chemical_list: D004338:Drug Combinations; D013449:Sulfonamides; D013148:Spironolactone; C026063:spironolactone, althiazide drug combination; D001215:Asparaginase
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