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Treatment of anti‐recombinant interferon‐alpha 2 antibody positive CML patients with natural interferon‐alpha
Author(s) -
Wussow P. v.,
Jakschies D.,
Freund M.,
Hehlmann R.,
Brockhaus F.,
Hochkeppel H.,
Horisberger M.,
Deicher H.
Publication year - 1991
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.1991.tb04418.x
Subject(s) - medicine , antibody , titer , alpha interferon , immunology , interferon alfa , gastroenterology , neutralizing antibody , interferon
Summary Of 38 patients with a Philadelphia‐chromosome positive chronic myeloid leukaemia treated with recombinant interferon alpha (rIFN‐α) 2a or 2b and monitored for emergence of IFN‐antibodies in their sera 11 patients developed rIFN‐α2 binding and 10 rIFN‐α2 neutralizing antibodies. rIFN‐α neutralizing antibody positive patients experienced significantly ( P <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‐α‐therapy than IFN‐antibody‐negative patients with titre below 400 INU/ml ( P <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‐α2. Only one of these seven patients developed a partial haematological remission upon intensification of the rIFN‐α2 therapy. Consecutively, the six patients failing high dose rIFN‐α treatment were switched to a natural IFN‐α preparation (3 × 9 × 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 Mxhomologue concentrations were measured; in contrast, nIFN‐α induced normal IFN‐titre and dose‐equivalent Mxhomologue amounts in these patients. The data prove that high‐titred rIFN‐α neutralizing antibodies abrogate the biological action of rIFN‐α, but not of nIFN‐α in vivo and explains why nIFN‐α can be effective in the anti rIFN‐α2 positive patients.