L‐asparaginase treatment in acute lymphoblastic leukemia

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. Cancer 2011;117:238-49.

Screening and characterization of extracelluar L-asparaginase producing Bacillus subtilis strain hswx88, isolated from Taptapani hotspring of Odisha, India

“…Treatment with LAse, polyphenoloxidase and low frequency laser decreased adhesion of uropathogenic Escherichia coli to human erythrocytes [4] . LAse also known commercially as Oncaspar, Colaspase, Crasnitin, Kidrolase, Erwinase and Elspar [5] . It is also used in food industry for the production of acrylamide (a potent carcinogen and a neurotoxic compound) free starchy fry food [6] .…”

“…The results of the morphological, biochemical and physiological tests were put into Bergey's Manual of Determinative Bacteriology [19] and bacterial identification software's like PIBwin version 2.0 and ABIS online for accurate identification. The isolate TPS-12 was exposed to temperature range of 40-100°C, pH range of [3][4][5][6][7][8][9][10][11][12] and sodium chloride concentrations range of 2%-10% for evaluation of physiological characteristics. The antibiogram pattern of the isolate TPS-12 was tested for sensitivity against different antibiotic discs (Himedia, Mumbai) viz., erythromycin (15 …”

“…The isolate TPS-12 when exposed to temperature range of 40-100 °C, showed growth in the temperature range of 150-70 °C, while the growth was restricted above and below the above specified range. The isolate TPS-12 when exposed to different pH range (3)(4)(5)(6)(7)(8)(9)(10)(11)(12) and tolerance to different concentrations of sodium chloride (2%-10%), exhibited growth at pH range of [5][6][7][8][9][10] and tolerated sodium chloride concentrations 2%-7% respectively. The isolate showed no growth at pH 3 The results of the antibiogram pattern revealed that the isolate TPS-12 was very sensitive to all the tested antibiotics.…”

In Vivo Imaging of Antileukemic Drug Asparaginase Reveals a Rapid Macrophage-Mediated Clearance from the Bone Marrow

“…Upon administration, this drug converts serum asparagine into aspartate, thereby effectively depleting the blood from this amino acid. Unlike most other cells in the body, lymphocytes, including leukemic blasts, are fully dependent on uptake of asparagine from the blood and die as a result of nutrient stress (1).…”

Cure trends in acute lymphoblastic leukemia: is it time for a revised concept of cure?

“…using dexamethasone instead of prednisolone, 7 and less so by the introduction of novel agents. More recently, therapy optimization focusses on asparaginase, including asparaginase dose intensification, therapeutic drug monitoring, and the use of novel pegylated formulations, as reviewed by Pieters et al 8 The progress made with these changes are not yet visible in the results reported by Gatta et al as these developments are too recent. At least as important are the improvements in supportive care reducing the number of patients dying from treatment-related mortality, 9 including developments in blood-banking, antibiotics and antifungals, parenteral nutrition and tumor lysis prevention.…”