Polypeptide of bacterial origin (E. coli) widely used in the treatment of acute lymphoblastic leukemia in children and adults.
Incidence
Highest of all antimitotic agents.
Intravenous route: 15 to 33%.
Intramuscular route: 6 to 18%.
Deaths reported.
Risk factors
Intravenous use.
Hiatus of 1 month or more between two courses.
Non-association with prednisone and vincristine.
Prior exposure months or years previously.
Clinical manifestations
General: anaphylactic shock.
Cutaneous: pruritus, rash, urticaria, angioedema.
Respiratory: laryngospasm, bronchospasm.
Diagnostic methods
Cutaneous testing.
Ineffective (false positive and negative).
Specific IgE.
Increased specific IgE antibodies found in patients in whom L-asparaginase infusions are followed by allergic reactions.
Specific IgM and IgG (microtiter solid-phase radioimmunoassay).
High titers of IgG3 or IgG4 anti L-asparaginase may predict L-asparaginase allergy.
Complement activation (C3d).
L-asparaginase-specific IgG antibodies bind and activate the complement system.
Mechanisms
IgE-mediated hypersensitivity: a few cases.
Complement activation induced by formation of immune complexes of L-asparaginase and specific IgM and IgG class antibodies.
Leukotriene production by bone marrow-derived mast cells.
Management
Avoidance, but hypersensitivity reactions to L-asparaginase do not impact on the remission duration in adults with acute lymphoblastic leukemia.
Use of alternative formulations:
- L-asparaginase derived from Erwinia chrysantemia: fewer anaphylactic reactions and no cross-reactivity with Escherichia coli L-asparaginase
- Polyethyleneglycol-L-asparaginase: lower immunogenicity.
Premedication (epinephrine).
Desensitization (in a 2-year-old child with myelogenous leukemia).
From 1.2 U/hour over 4.2 hours to 1200 U/hour over 3.8 hours.