CLINICAL AND BIOLOGICAL EFFECTS OF GAMMA-INTERFERON AND THE COMBINATION OF GAMMA-INTERFERON AND INTERLEUKIN-2 AFTER AUTOLOGOUS BONE-MARROW TRANSPLANTATION

Interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) have shown syner gistic immunomodulatory and anti-tumor effects in preclinical studies. The present study was designed to assess the effects of the combinati on of these cytokines after autologous bone marrow transplantation (AB MT). Ten patients received rIFN-gamma alone and 13 patients the combin ation of rIFN-gamma + rIL-2. Patients received transplants because of lymphoma (10 patients), acute leukemia (3 patients) or solid tumors (1 0 patients). Immunotherapy was started at a median of 67 days after AB MT. All patients received either 5 x 10(6) (8 pts) or 10 x 10(6) IU/m( 2) (16 pts) rIFN-gamma by subcutaneous injection 3 times weekly for 14 weeks, rIL-2 therapy consisted of 5 cycles of continuous intravenous infusion of 12 x 10(6) IU/m(2)/day starting 1 week after administratio n of rIFN-gamma, In the rIFN-gamma group, toxicity was mild and some b iological changes were seen (NK/LAK activation, increase of phagocytos is and of NBT reduction). The combination of rIFN-gamma with rIL-2 did not increase the usual rIL-2 toxicity. NK/LAK cytotoxicity was strong ly activated after the first cycle of rIL-2 and was maintained until t he end of therapy. Granulocyte chemotaxis was defective after cycle 1 but recovered thereafter. We conclude that the administration of rIFN- gamma + rIL-2 is feasible after ABMT. Our data suggest that the combin ation may have prolonged the immunologic activation provided by rIL-2 and some improvement of the deleterious effects of rIL-2 on granulocyt e functions was achieved. Controlled studies are warranted to assess t he impact of this strategy on biological response and patient outcome.