Low incidence of antibody formation due to long-term interferon-alpha 2c treatment of cancer patients.

In order to study the long-term immunogenicity of interferon-alpha 2c (Berofor) in cancer patients, serum was collected starting in 1983 from study patients with various proliferative diseases who received interferon-alpha 2c at different doses, according to different schedules, and via different routes. A total of 1992 samples were tested for the presence of anti-interferon-alpha 2c antibodies. Due to long-term interferon-alpha 2c treatment, 346 patients were eligible for induction of neutralizing anti-interferon antibodies over a treatment period of 2-52 months. Most patients were treated for longer than 6 months. Of the 346 patients, three patients (0.87%) exhibited measurable titers of neutralizing antibodies following therapy with interferon-alpha 2c. One hundred and sixty-three patients suffered from non-Hodgkin lymphomas, leukemias, and preleukemias. One patient with chronic myeloid leukemia experienced antibody induction under therapy. The other 183 patients had solid tumors. Two of them reacted with antibody production. All titers were very low (1:12, 1:8, and 1:64). Compared with figures reported for other interferon-alpha preparations, the propensity of interferon-alpha 2c to induce neutralizing antibodies seems to be very low. This property might be related to arginines occurring as critical residues in positions 23 and 34 of the interferon-alpha 2c molecule.

Clinical implications of increased plasma levels of CD8 in patients with hairy cell leukemia.

Plasma levels of soluble T-suppressor/cytotoxic antigen (sCD8) were measured at diagnosis or before systemic treatment in 69 patients with hairy cell leukemia (HCL). The 49 nonsplenectomized patients were characterized by high concentrations of sCD8 antigen as compared with 17 controls (P less than .0001). The median sCD8 level in non-splenectomized patients was 1,050 U/mL (range: 160 to 2,400 U/mL) and was significantly higher (P less than .0001) than the median of 275 U/mL (range: 20 to 1,080 U/mL) in splenectomized patients. The relationship of sCD8 to clinical response to subsequent interferon alpha (IFN alpha) treatment was analyzed. Patients who showed subsequent hematologic response with normalization of all blood counts had significantly lower levels of sCD8 concentrations at diagnosis than those who did not (P = .0056). Furthermore, normalization of sCD8 during IFN alpha treatment paralleled the achievement of normal counts in peripheral blood, whereas soluble interleukin-2 receptor (sIL-2R) levels remained high in most patients after 12 to 15 months of treatment. We speculate that activation of suppressor/cytotoxic T cells might play a role in myelosuppression, and its modulation during treatment with IFN alpha correlates with normalization in peripheral blood counts.