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Effective natural interferon-alpha therapy in recombinant interferon-
alpha-resistant patients with hairy cell leukemia
P von Wussow, H Pralle, HK Hochkeppel, D Jakschies, S Sonnen, H Schmidt, D Muller-Rosenau, M Franke, T Haferlach and T Zwingers
Department of Immunology, Medical School of Hanover, Germany.
To explore the relationship between anti-interferon-alpha (anti-IFN- alpha)
antibodies and loss of clinical responsiveness to IFN-alpha treatment, we
examined sera from 59 patients with hairy cell leukemia who responded to
therapy with recombinant IFN-alpha-2a (rIFN-alpha-2a). During the first 2
years of therapy, 10 patients developed rIFN-alpha- 2a-neutralizing and 15
rIFN-alpha-2a-binding antibodies. Nine of the 59 initially responding
patients became resistant to rIFN-alpha-2a and suffered a relapse of the
disease at 7 to 24 months of treatment. All nine relapsing patients tested
positive for both neutralizing and binding antibodies with titers above 400
INU/mL, while none of the antibody-negative patients relapsed. Six patients
with detectable binding antibody titers below 400 INU/mL continued to
respond to treatment. By measuring the IFN kinetics and the levels of the
IFN- induced Mx-homologous protein in mononuclear cells after a single
injection each of rIFN-alpha-2a and nIFN-alpha the IFN antibodies of eight
of the nine resistant rIFN-alpha patients were found to be highly specific
for rIFN-alpha-2a. Therefore, these eight patients were switched to natural
IFN-alpha (nIFN-alpha) therapy at doses of 3 million IU, three times a
week. All eight patients responded to treatment with nIFN-alpha, achieving
durable objective responses similar to those obtained previously with
rIFN-alpha-2a. These data clearly demonstrate that rIFN-alpha
antibody-positive patients can effectively be treated with nIFN-alpha.
Volume 78,
Issue 1,
pp. 38-43,
07/01/1991
Copyright © 1991 by The American Society of Hematology
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