Back to the future: the amazing journey of the therapeutic anti-leukemia enzyme asparaginase <i>Erwinia chrysanthemi</i>

Abstract

For several decades asparaginase has been considered world-wide as an essential component of combination chemotherapy for the treatment of childhood acute lymphoblastic leukemia (ALL). Discovered over 60 years ago, two main unmanipulated asparaginase products originated from primary bacteria sources, namely Escherichia coli and Erwinia chrysanthemi, have been available for clinical use. A pegylated product of the Escherichia coli asparaginase was subsequently developed and is now the main product used by several international cooperative groups.&#x0D; The various asparaginase products all display the same mechanism of action (hydrolysis of circulating asparagine) and are associated with similar efficacy and toxicity patterns. However, their different pharmacokinetics, pharmacodynamics and immunological properties require distinctive modalities of application and monitoring.&#x0D; Erwinia chrysanthemi asparaginase was initially used as a first-line product, but subsequently became a preferred second-line product for children who experienced immunological reactions to the Escherichia coli asparaginase products. An asparaginase product displaying the same characteristics of the Erwinia chrysanthemi asparaginase recently has been produced by use of recombinant technology, thus securing a preparation available for use as an alternative, or as a back-up in case of shortages, for the non-recombinant product.&#x0D; The long journey of the Erwinia chrysanthemi asparaginase product as it has developed throughout the last several decades has made it possible for almost every child and adult with ALL to complete the asparaginase-based protocol treatment when an immunological reaction has occurred to any Escherichia coli asparaginase product.

Comment on: Desensitization using PEGasparaginase in the era of commercially available Erwinia: A single‐institution report on efficacy, cost, and resource utilization

“…1 Finally, Feldman et al studied the costs in their cost analysis, revealing that substantial savings were found when ALL patients received desensitization over the now commercially available recombinant Erwinia asparaginase, Rylaze. 16 Back to the future, Tong et al published their cost analysis focusing on asparaginase preparations. They concluded that the cost of the intensification course of 30 weeks was $57,893 US dollars (€1 = $1.40 US dollar, according to the price level in 2010, and Dutch tariffs).…”