Clinical and laboratory changes induced by alpha interferon in chronic lymphocytic leukemia‐a pilot study

Abstract

Ten chronic lymphocytic leukemia patients were treated with partially pure alpha interferon (IFN-alpha) at doses ranging from 3-9 X 10(6) units administered intramuscularly daily. Of these patients, three patients with disease stages 0, 1, and 3 (and prolymphocytic leukemia), respectively, responded with partial remissions lasting from 10 to 24+ months; four additional patients had minor responses. Among those responding, modulation of B cell chronic lymphocytic leukemia, surface immunoglobulins, and surface antigens were observed in four patients. These changes included a decline in the proportion of B cells bearing surface immunoglobulin without change in the number of the B cells. Likewise, a decline in the proportion of B cells bearing T-1 antigen was observed in three patients. Increase in the percentage of T cells, primarily the T helper cells, was seen in two of the responding patients. Specific binding of alpha interferon was demonstrated prior to therapy in CLL cells of all patients. This binding declined rapidly following treatment with IFN-alpha. Induction of the enzyme 2'5' oligoisoadenylate synthetase was examined in CLL patients prior to and during therapy with IFN-alpha. Variable levels of the enzyme were induced in all patients on therapy; however, only minimal induction was observed in two of three patients failing therapy.

Interleukin-7 treatment counteracts IFN-α therapy-induced lymphopenia and stimulates SIV-specific cytotoxic T lymphocyte responses in SIV-infected rhesus macaques

“…IFN-␣-based therapy was the first and remains one of the most used treatments for viral infections, such as hepatitis C 33 as well as an immunomodulating compound for stimulation of specific immunity in advanced cancers. [34][35][36][37] Despite its efficacy, IFN-␣ treatment is always associated with significant side effects. Among these, the development of lymphopenia often limits its use, particularly in those patients who have received aggressive chemotherapy or who have T-cell depletion, such as that associated with chronic HIV infection.…”

Interferon‐alpha 2b (IFNα) for Early‐Phase Chronic Lymphocytic Leukaemia with High Risk for Disease Progression: Results of a Randomized Multicentre Study

“…IFN is considered to be ineffective (Foon et al, 1984;Horning et al, 1985) in advanced CLL, and response rates in the range of 30-71% were reported in early disease (Schulof et al, 1985;O'Connell et al, 1986;Talpaz et al, 1987;Boussiotis & Pangalis, 1988, 1991Rozman et al, 1988;Pangalis & Griva, 1988;Ziegler-Heitbrock et al, 1989;Molica & Alberti, 1990;McSweeney et al, 1993;Morabito et al, 1993). However, all these studies were uncontrolled phase II trials which determined response rates as major endpoints.…”

“…Moreover, in one study, treatment with chlorambucil was associated with a shorter survival due to the higher incidence of secondary malignancies (French Cooperative Group on Chronic Lymphocytic Leukemia, 1990a). Interferon alpha was not effective in advanced CLL (Foon et al, 1984;Horning et al, 1985), but several phase II studies demonstrated the activity of recombinant IFN in previously untreated early-stage patients, where partial responses could be achieved in 30-70% of patients (Schulof et al, 1985;O'Connell et al, 1986;Talpaz et al, 1987;Boussiotis & Pangalis, 1988, 1991Rozman et al, 1988;Pangalis & Griva, 1988;Ziegler-Heitbrock et al, 1989;Molica & Alberti, 1990;McSweeney et al, 1993;Morabito et al, 1993). Therefore, to assess the value of IFN for the prevention of disease progression of early-stage CLL, a risk-adapted multicentric phase III study was conducted.…”

Interferon and Malignant Disease - How Does it Work and Why Doesn't it Always?

“…Several studies have shown a correlation between the in vitro susceptibility of primary malignant cells to IFN and the clinical response of the patient to IFN therapy (22)(23)(24)(25)(26). This correlation is in sharp contrast to the data for the indirect antitumour effects of IFN: indeed, the fact that a clinical response is not seen if the malignant cells are completely insensitive to IFN strongly supports the idea that the antitumour effects of IFN result mainly from direct effects on the tumour cells.…”