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. Cancer 2011;117:238-49.
The trial ALL-BFM 95 for treatment of childhood acute lymphoblastic leukemia was designed to reduce acute and longterm toxicity in selected patient groups with favorable prognosis and to improve outcome in poor-risk groups by treatment intensification. These aims were pursued through a stratification strategy using white blood cell count, age, immunophenotype, treatment response, and unfavorable genetic aberrations providing an excellent discrimination of risk groups.
The present study quantified an often observed but so far hardly assessable problem. Activity in cancer patients is considerably reduced and patients with bone tumors are at increased risk from the detrimental effects of prolonged inactivity. Both our findings and the accepted fact that activity is an essential element of child development confirm the need for interventions tailored to a patient's needs and abilities during the course of treatment.
ABSTRACTweeks for a total of 15 doses (Online Supplementary Figure S1). In case of an allergy to or silent inactivation of PEGasparaginase, the patient was switched to Erwinia asparaginase as the second-line agent (20,000 IU/m 2 per dose) 2-3 times per week to complete 30 weeks of asparaginase therapy. In the case of high asparaginase activity levels (72 hours ≥100 U/L), the frequency of Erwinia asparaginase infusions was reduced to twice weekly.6 Both asparaginase preparations were administered intravenously over 1 hour.
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