asparaginase IgE

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In a series of 40 patients treated with L-asparaginase for various neoplastic diseases, 6 patients had generalized anaphylactic reactions to L-asparaginase. Each of these reactors had antibodies detectable by passive hemagglutination, but precipitins were detectable in only one of this group of six patients. That patient had received two courses of the enzyme. 1 wk after the anaphylactic reaction, complement-fixing antibodies were present in all the patients that were studied. Specific reagin antibodies (IgE) were demonstrated in one patient by the release of histamine from his leukocytes after incubation in vitro with L-asparaginase...

Suppression of anti-L-asparaginase (anti-A-ase) IgG and IgE antibody responses was achieved in Balb/c mice with polyethylene glycol (PEG, MW, 5,000) conjugated Escherichia coli A-ase. Following the administration of the mixture of A-ase and PEG-A-ase, antibody production to A-ase was reduced. PEG-A-ase administration prior to A-ase suppressed the primary and secondary responses to A-ase antibody. The suppression could be transferred to normal mice with spleen cells from A-ase tolerant mice. The cell transfer experiment showed that the suppression was caused by suppressor T cells...

L-Asparaginase (l-Asp) is widely used as an effective drug against childhood and adult acute lymphoblastic leukemia (ALL). However, it is immunogenic in humans and may lead to hypersensitivity reactions. The immunological basis of these reactions is not clear. Since the presence of l-Asp specific IgG-antibodies seems to correlate better with clinical reactions than IgE-antibodies and IgG-antibodies are known to be able to fix and activate the complement system, we speculated that the mechanism of anaphylaxis may be complement- rather than IgE-mediated...

By using a modification of the microtiter solid-phase radioimmunoassay, we have measured Escherichia coli L-asparaginase (L-ASP) specific IgG, IgG4, and IgE antibodies in children who received L-ASP as part of their chemotherapy for leukemia and lymphoma. In 13 children with acute lymphoblastic leukemia induced with vincristine, prednisone, and L-ASP (10,000 IU/M2 i.v. each week for 3 weeks), seven developed high titer specific IgG antibodies. Four of the seven relapsed at the time of their peaking IgG response (6-10 months)...

The formation of specific IgE antibodies to L-Asp was studied in 27 children with ALL. Increased titers of specific IgE antibodies were significantly more frequent (p less than 0.001) prior to L-Asp infusions followed by allergic reactions than in those without reactions. After passive sensitization of basophile granulocytes of a healthy volunteer using patient's serum with the highest titers of specific IgE antibodies to L-Asp a significant release of histamine was observed after exposure of cells to L-Asp...

All cancer chemotherapeutic agents, except altretamine, the nitrosoureas, and dactinomycin, have produced at least an isolated instance of a HSR. Certain drugs, such as L-asparaginase and mitomycin (administered intravesically), cause HSRs of significant degree in approximately 10% of patients. All four types of HSRs are represented in the reactions produced by antitumor drugs, although Type I is the most common. Some of the Type I reactions are IgE-mediated, and others are probably mediated by nonspecific release of vasoactive substances from targets such as mast cells...

One hundred and fourteen patients with acute leukemia, 57 children (10 AML and 47 ALL) and 57 adults (37 AML and 20 ALL) were treated with L-asparaginase (Asnase) 200 or 1000 IU/kg daily for 30 days unless withdrawn on account of side effects. Combinations with other cytotoxic drugs were used in all but eight patients. Hypersensitive reactions, decrease in Asnase activity in plasma, and bivalent antibodies to Asnase appeared more frequently in adults (28%, 46%, and 79%, respectively) than in children (16%, 17%, and 25% respectively)...

The following in vitro methods are predominantly discussed: Specific IgE determination (RAST). The test can be used to detect allergies of the immediate type such as anaphylactic shock and urticaria. Antibodies can be detected to a limited number of drugs such as penicillin, ACTH, TSH, insulin, asparaginase and proteins of animal sources. Degranulation of basophil leucocytes and histaminliberation have been used for many years. The practical value of the test has been limited but improved methods for analysis have given the tests hopes for a come-back...