L-Asparaginase


L-Asparaginase (Kidrolase™ or Elspar™) is a catalyst of the hydrolysis of L-asparagin into aspartic acid and ammonium, resulting in the deprivation of blood L-asparaginase. Some leukaemic lymphoblasts and other tumour cells have a very low intracytoplasmic level of L-asparagine synthetase and cannot synthesise it de novo.

It is a protein enzyme extracted from cultures of Escherichia coli, and which may be very selective for tumour cells. However, tumour cells very rapidly deregulate the enzyme’s synthesis and become resistant to L-Asparaginase.

Indications

The main indications of L-Asparaginase are haematological, the action on solid tumours being very irregular:

Acute lymphoblastic leukaemia,

Leukaemic meningitis,

Non Hodgkin's lymphoma

Dosage

This treatment can be administered either intravenously, intramuscularly or by thecal injections.

The usual dosage is from 500 to 1.000 UI / kg / day or 7.500 to 10.000 UI / m2 / day for adults.

Main toxicities

Only specific toxicities (or major toxicities) are described here. Other common chemotherapy toxicities are described in the chapter on chemotherapy toxicity.

Hypersensitivity

This side-effect is very frequent: it provokes nettle rashes, more rarely laryngeal oedema or bronchospasm or genuine anaphylactic shock. The treatment should be immediately and definitively stopped.

Inhibition of protein synthesis

It corresponds to the diminution of endogen synthesis of L-asparagine in normal cells.

Thus, patients who already present a slight spontaneous diminution in a specific synthesis might suffer from complications due to strong diminution of synthesis of various factors such as fibrinogen, antithrombin III, plasminogen, coagulation factors VII, IX, X and VIII. Such diminution can be the cause of coagulation disorders, haemorrhage or thrombosis.

Other potentially affected factors include albuminemia, insulin or serum lipoproteins.

For a few patients, the diminution of the brain concentration of L-asparagine may be responsible for dizziness, confusion, stupor or even coma.

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