title: Treatment of anti-recombinant interferon-alpha 2 antibody positive CML patients with natural interferon-alpha.
abstract: Of 38 patients with a Philadelphia-chromosome positive chronic myeloid leukaemia treated with recombinant interferon alpha (rIFN-alpha) 2a or 2b and monitored for emergence of IFN-antibodies in their sera 11 patients developed rIFN-alpha 2 binding and 10 rIFN-alpha 2 neutralizing antibodies. rIFN-alpha neutralizing antibody positive patients experienced significantly (P less than 0.025) more clinical relapses (6/10) than IFN-antibody negative patients (6/28) during continuous IFN-therapy. Furthermore, IFN-antibody-positive patients with titre above 400 INU/ml were more likely to relapse under rIFN-alpha-therapy than IFN-antibody-negative patients with titre below 400 INU/ml (P less than 0.05). Seven rIFN-antibody-positive patients experiencing a clinical relapse or a primary non-responsiveness were treated with two- to three-fold increased doses of rIFN-alpha 2. Only one of these seven patients developed a partial haematological remission upon intensification of the rIFN-alpha 2 therapy. Consecutively, the six patients failing high dose rIFN-alpha treatment were switched to a natural IFN-alpha preparation (3 x 9 x 10(6) I.U. weekly s.c.). Under such treatment two of the six patients achieved a long-lasting complete, one a partial haematological remission. In high-titred IFN-antibody positive patients significantly altered serum-IFN-titre and minimal IFN-inducible Mx-homologue concentrations were measured; in contrast, nIFN-alpha induced normal IFN-titre and dose-equivalent Mx-homologue amounts in these patients. The data prove that high-titred rIFN-alpha neutralizing antibodies abrogate the biological action of rIFN-alpha, but not of nIFN-alpha in vivo and explains why nIFN-alpha can be effective in the anti rIFN-alpha 2 positive patients.
authors.affiliation: Department of Immunology and Transfusion Medicine, Medical School of Hannover, West Germany.
authors.forename: P V
authors.initials: PV
authors.lastname: Wussow
authors.forename: D
authors.initials: D
authors.lastname: Jakschies
authors.forename: M
authors.initials: M
authors.lastname: Freund
authors.forename: R
authors.initials: R
authors.lastname: Hehlmann
authors.forename: F
authors.initials: F
authors.lastname: Brockhaus
authors.forename: H
authors.initials: H
authors.lastname: Hochkeppel
authors.forename: M
authors.initials: M
authors.lastname: Horisberger
authors.forename: H
authors.initials: H
authors.lastname: Deicher
mesh_terms: D000912:Antibodies, Neoplasm / Q000032:analysis; D000998:Antiviral Agents / Q000097:blood; D001798:Blood Proteins / Q000032:analysis; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000097:blood / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000276:immunology* / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000628:therapy*; D008297:Male; D011994:Recombinant Proteins
chemical_list: D000912:Antibodies, Neoplasm; D000998:Antiviral Agents; D001798:Blood Proteins; D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins