Treatment of anti-recombinant interferon-alpha 2 antibody positive CML patients with natural interferon-alpha.
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.
Wussow
P V
PV
Department of Immunology and Transfusion Medicine, Medical School of Hannover, West Germany.
Jakschies
D
D
Freund
M
M
Hehlmann
R
R
Brockhaus
F
F
Hochkeppel
H
H
Horisberger
M
M
Deicher
H
H
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
D000912:Antibodies, Neoplasm; D000998:Antiviral Agents; D001798:Blood Proteins; D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins