Asparaginases are important agents used in the treatment of children with
acute lymphoblastic leukemia (ALL). Three types of
asparaginase are currently available: two are derived from Escherichia coli [native
asparaginase and
pegylated asparaginase (
PEG-asparaginase)] and one from Erwinia chrysanthemi (crisantaspase). All three products share the same mechanism of action but have different pharmacokinetic properties, which do not make them easily interchangeable. Among the known toxicities and side-effects,
allergic reactions and silent inactivation represent the most important limitations to the prolonged use of any
asparaginase product, with associated reduced
therapeutic effects and poorer outcomes. Routine real time monitoring can help to identify patients with silent inactivation and facilitate a switch to a different product to ensure continued depletion of
asparagine, completion of the treatment schedule and maintenance of outcomes. However, the most appropriate second-line treatment is still a matter of debate.
PEG-asparaginase has lower immunogenicity and a longer half-life than native Escherichia coli (E. coli)
asparaginase, which makes it useful for both first-line and second-line use with a reduced number of doses. However,
PEG-asparaginase displays cross-reactivity with native E. coli
asparaginase that may harm its
therapeutic effects. Crisantaspase does not display cross-reactivity to either of the E. coli-derived products, which has made crisantaspase the second-line treatment option in a number of recent protocols. As crisantaspase has a much shorter
biological half-life than the E. coli-derived products, the appropriate dosage and administration schedule are of paramount importance in delivering treatment with this product. In the ongoing trial AIEOP-BFM ALL 2009 (Associazione Italiana Ematologia Oncologia Pediatrica - Berlin-Franklin-Munster), in which
PEG-asparaginase is used first-line, one dose of
PEG-asparaginase is substituted by seven doses of crisantaspase given intravenously at 20,000 IU/m2 on alternate days when clinical
allergy or silent inactivation is present. Based on the indications of different protocols, lack of cross-reactivity to the E. coli-derived products and taking into consideration regulatory factors and availability, crisantaspase may be considered a viable second-line
therapy.