PHASE-I TRIAL OF INTERFERON-GAMMA TO POTENTIATE CYCLOSPORINE-INDUCED GRAFT-VERSUS-HOST DISEASE IN WOMEN UNDERGOING AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR BREAST-CANCER

Purpose: We investigated if interferon gamma (IFN-γ) could augment cyclosporine (CSA)-induced graft-versus-host disease (GVHD) following autologous bone marrow transplant in women with metastatic breast cancer and defined the toxicities of this therapy. Patients and Methods: Thirty-six women with advanced breast cancer were treated with CSA 2.5 mg/kg daily for 28 days and IFN-γ 0.025 mg/m2 subcutaneously (SC) every other day, days 7 to 28 following autologous bone marrow transplantation and monitored for induction and severity of GVHD and toxicity of therapy. Results: GVHD was induced in 56% of patients. The severity of GVHD was greater than in a historic control population treated with CSA alone. Stage III rash was seen in 36% of patients, compared with 3% in the historic control population. Fourteen of 36 patients required therapy with topical corticosteroids and two of 36 required systemic treatment. Only three of 31 historic controls needed topical corticosteroids and no patient was treated systemically. There was no severe visceral GVHD. Hematopoietic recovery was not delayed. There were three toxic deaths. Conclusion: CSA-induced GVHD can be safely augmented by IFN-γ in women treated with high-dose alkylating agents and autologous bone marrow transplantation. There is little evidence of increased toxicity. Evidence of antitumor efficacy awaits further investigation.