Clinical and biological effects of gamma interferon and the combination of gamma interferon and interleukin-2 after autologous bone marrow transplantation

Interferon-gamma (IFN-γ) and interleukin-2 (IL-2) have shown synergistic immunomodulatory and anti-tumor effects in preclinical studies. The present study was designed to assess the effects of the combination of these cytokines after autologous bone marrow transplantation (ABMT). Ten patients received rIFN-γ alone and 13 patients the combination of rIFN-γ + rIL-2. Patients received transplants because of lymphoma (10 patients), acute leukemia (3 patients) or solid tumors (10 patients). Immunotherapy was started at a median of 67 days after ABMT. All patients received either 5 x 106 (8 pts) or 10 x 106 IU/m2 (16 pts) rIFN-γ by subcutaneous injection 3 times weekly for 14 weeks. rIL-2 therapy consisted of 5 cycles of continuous intravenous infusion of 12 x 106 IU/m2/day starting 1 week after administration of rIFN-γ. In the rIFN-γ group, toxicity was mild and some biological changes were seen (NK/LAK activation, increase of phagocytosis and of NBT reduction). The combination of rIFN-γ with rIL-2 did not increase the usual rIL-2 toxicity. NK/LAK cytotoxicity was strongly activated after the first cycle of rIL-2 and was maintained until the end of therapy. Granulocyte chemotaxis was defective after cycle 1 but recovered thereafter. We conclude that the administration of rIFN-γ + rIL-2 is feasible after ABMT. Our data suggest that the combination may have prolonged the immunologic activation provided by rIL-2 and some improvement of the deleterious effects of rIL-2 on granulocyte functions was achieved. Controlled studies are warranted to assess the impact of this strategy on biological response and patient outcome.