Crisantaspase

Synonyms: asparaginase

Crisantaspase is an enzyme, asparaginase, derived from the bacterium Erwinia chrysanthemi. A lot of progress in the treatment of acute lymphoblastic leukaemias has been made over the last 30 years using combinations of drugs including crisantaspase.¹ Now 80% of patients can be cured, although clinical subgroups with a poor prognosis can be identified (for example those with central nervous system disease).²

Asparagine is important for protein synthesis in leukaemia cells (it cannot be synthesised without the enzyme asparaginase synthase). Crisantaspase (asparaginase) depletes leukaemia cells of asparagine so blocking protein synthesis and cell proliferation. It also causes apoptosis. In many cases patients develop drug-resistant forms of the disease which correlate with up-regulation of the enzyme glutamine dependent asparagine synthetase, although may not be linked directly to the up-regulation.³ Newer derivatives of the drug are proving useful in the treatment of relapsed or refractory leukaemias.^4,5

Crisantaspase is a major component of regimens for the treatment of acute lymphoblastic leukaemia (ALL), particularly in children, but some debate exists about the best formulation and dosage.⁶ It is a crucial drug in the induction therapy for ALL. It should be used as part of regimens designed and initiated in specialist treatment centres.

It is given intravenously through central or peripheral line but can also be given intramuscularly and subcutaneously. Asparaginase derived from E. coli has been found to be superior but more toxic than that derived from Erwinia chrysanthemi. ⁶ A review of the different types shows that newer preparations show advantages over older, native preparations.^5,7,8

Pregnancy and breastfeeding.

Caution with aspirin and anticoagulants. Crisantaspase affects production of clotting factors in the liver and thus may cause changes in blood clotting, occasionally with bruising or bleeding. Such effects may be exacerbated with concomitant use of aspirin or anticoagulants.

• Itchy rash and fever occur commonly.
• Other significant side effects include:
  • Nausea and vomiting.
  • Loss of appetite.
  • Coagulation disorders (causing bruising and bleeding).
  • Liver function changes.
  • Pancreatitis.
  • Hyperglycaemia.
  • Lipid changes.
• As it is a protein, allergic reactions can occur.
• Hair loss is not a problem with crisantaspase.

This should be coordinated in specialist treatment centres and incorporate monitoring of the disease being treated as well as monitoring for adverse effects of treatment. Patients are warned of symptoms of hyperglycaemia (thirst, polyuria) and given instructions in testing for glycosuria. Facilities for the management of anaphylaxis should be available when administered.

Shared care protocols with details of the drug regimens and detail about drugs within the particular regimen should be sought from the treatment centres.