title: Effective natural interferon-alpha therapy in recombinant interferon-alpha-resistant patients with hairy cell leukemia.
abstract: 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.
authors.affiliation: Department of Immunology, Medical School of Hanover, Germany.
authors.forename: P
authors.initials: P
authors.lastname: von Wussow
authors.forename: H
authors.initials: H
authors.lastname: Pralle
authors.forename: H K
authors.initials: HK
authors.lastname: Hochkeppel
authors.forename: D
authors.initials: D
authors.lastname: Jakschies
authors.forename: S
authors.initials: S
authors.lastname: Sonnen
authors.forename: H
authors.initials: H
authors.lastname: Schmidt
authors.forename: D
authors.initials: D
authors.lastname: Müller-Rosenau
authors.forename: M
authors.initials: M
authors.lastname: Franke
authors.forename: T
authors.initials: T
authors.lastname: Haferlach
authors.forename: T
authors.initials: T
authors.lastname: Zwingers
mesh_terms: 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
chemical_list: D004274:DNA, Recombinant; D007370:Interferon Type I