Asparaginase Erwinia chrysanthemi as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia who have developed hypersensitivity to E. coli-derived asparaginase

SUMMARY

Asparaginase has been a mainstay of therapy in the treatment of acute lymphoblastic leukemia since the 1970s. There are two major preparations available and FDA approved in the United States today, one derived from Escherichia coli and the other from Erwinia chrysanthemi. Erwinia asparaginase is antigenically distinct from and has a considerably shorter biological half-life than E coli asparaginase. Erwinia asparaginase has been used in cases of hypersensitivity to E. coli-derived asparaginases, which has been reported in up to 30% of patients. While PEG asparaginase is increasingly used in front-line therapy for ALL, hypersensitivity still occurs with this preparation, and a change to a non-cross-reactive preparation may be necessary.

KEYWORDS:

• Asparaginase
• leukemia
• hypersensitivity
• pancreatitis
• thrombosis

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

• Asparaginase remains a vital component of acute lymphoblastic leukemia therapy.

• There are two asparaginase products available in the US: a pegylated form of Escherichia coli-derived asparaginase called polyethylene glycol (PEG) asparaginase and Erwinia chrysanthemi-derived asparaginase.

• Hypersensitivity is the most common toxicity of asparaginase therapy and limits the further use of the drug.

• Erwinia asparaginase is immunologically distinct from the E. coli-derived asparaginases, and therefore, most individuals will tolerate Erwinia asparaginase when a clinical allergy occurs after exposure to native E. coli asparaginase or PEG asparaginase.

• Erwinia asparaginase has a shorter half-life compared to E. coli asparaginase, and therefore, more frequent dosing is necessary to achieve adequate asparagine depletion.

• When dosed appropriately, there was no difference in efficacy between the different drug preparations.