Antibody response to Escherichia coli L-asparaginase. Prognostic significance and clinical utility of antibody measurement.
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). None of the six with low or absent L-ASP antibody response have relapsed (followed for 20-35 months). In six children with allergic reactions to L-ASP reinduction, all had high titers of L-ASP specific IgG4 (greater than or equal to 20 U/ml) at the time of their reaction. In 16 other children with low L-ASP IgG4 (less than 13 U/ml), none demonstrated allergic reactions to rechallenge. Specific IgE was not consistently detectable in either group. In 21 patients with leukemia or lymphoma on L-ASP with cyclophosphamide-containing regimens, none developed significant IgG antibody response, compared with seven of 13 not receiving cyclophosphamide (p less than 0.001). We conclude: (a) development of L-ASP antibodies may have prognostic significance; (b) the detection of specific IgG4 can predict L-ASP allergy; and (c) cyclophosphamide-containing regimens reduce antibody formation to L-ASP and may allow repetitive (without anaphylaxis) and more effective (avoiding neutralizing antibodies) use of L-ASP.
D000293:Adolescent; D000917:Antibody Formation / Q000187:drug effects*; D001215:Asparaginase / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004926:Escherichia coli / Q000201:enzymology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007073:Immunoglobulin E / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007223:Infant; D007700:Kinetics; D007945:Leukemia, Lymphoid / Q000188:drug therapy / Q000276:immunology*; D008223:Lymphoma / Q000188:drug therapy / Q000276:immunology*; D008297:Male; D011379:Prognosis; D011863:Radioimmunoassay / Q000379:methods
D007074:Immunoglobulin G; D007073:Immunoglobulin E; D001215:Asparaginase