Is asparaginase a critical component in the treatment of acute lymphoblastic leukemia?

The outcome of pediatric acute lymphoblastic leukemia (ALL) has improved dramatically over the last 40 years through a systematic approach of well-designed large trials including use of asparaginase. Although asparaginase has been incorporated with other drugs in adult ALL protocols, it has been associated with more toxicities in older patients resulting in caution in the inclusion of asparaginase-containing regimens for adults. Consequently, to date, no randomized trials with asparaginase have been performed in adults. Furthermore, adult regimens that do not include asparaginase have shown comparable outcomes to regimens with asparaginase, which makes the necessity of asparaginase in adult regimens unclear. There are several other factors which influence the role of asparaginase use in adults, including the level and sustainability of asparagine depletion, schedule, dosing, and form of asparaginase and the consequent toxicities and immunogenicity reactions.