Effective natural interferon-alpha therapy in recombinant interferon- alpha-resistant patients with hairy cell leukemia

To explore the relationship between antiinterferon-a (antiIFN-a) antibodies and loss of clinical responsiveness to IFN-a treatment, we examined sera from 59 patients with hairy cell leukemia who responded to therapy with recombinant IFN&?a (rlFN-cr-2a). During the first 2 years of therapy, 10 patients developed rlFN-a-2a-neutralizing and 15 rlFN-a-2abinding antibodies. Nine of the 59 initially responding patients became resistant to rlFN-a-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 TH THE AVAILABILITY of recombinant DNA technology, genetically engineered cytokines have rapidly become a therapeutic option in the treatment of malignant and infectious diseases. The most dramatic illustration of the efficacy of recombinant interferon-a (rIFN-a) has been in the treatment of hairy cell leukemia (HCL). Numerous studies have shown that approximately 90% of patients with HCL respond to treatment with rIFN-a, including those in whom splenectomy and other forms of systemic therapy have failed.’-5 Sustained responses are typically obtained with continued rIFN-a therapy, and the mean duration of response is in excess of 3 years. In contrast to conventional treatment, rIFN-a therapy alleviates cytopenia in almost all patients, resulting in a significant decrease in the need for tiansfusions and a pronounced reduction in the frequency and severity of infections. The enhanced survival and improvement in quality of life achieved with rIFN-a in HCL has made it the most successful example of the clinical use of biologic response modifiers to date. During therapy with rIFN-a, both IFN-binding and IFN-neutralizing antibodies can emerge. The incidence and clinical significance of these antibodies has been as yet a matter of considerable controversy. However, in several studies the presence of neutralizing antibodies has coin