Effective natural interferon-alpha therapy in recombinant interferon-alpha-resistant patients with hairy cell leukemia.
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.
von Wussow
P
P
Department of Immunology, Medical School of Hanover, Germany.
Pralle
H
H
Hochkeppel
H K
HK
Jakschies
D
D
Sonnen
S
S
Schmidt
H
H
Müller-Rosenau
D
D
Franke
M
M
Haferlach
T
T
Zwingers
T
T
D000328:Adult; D000368:Aged; D004274:DNA, Recombinant / Q000235:genetics*; D004341:Drug Evaluation; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000592:standards / Q000627:therapeutic use*; D007943:Leukemia, Hairy Cell / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged
D004274:DNA, Recombinant; D007370:Interferon Type I