Immune modulation in autologous bone marrow transplantation: cyclosporine and gamma-interferon trial

From March 1994 to November 1994, 16 patients with high risk hematological malignancies were entered in a phase I clinical trial, designed to confirm the toxicity of cyclosporine and gamma interferon given to induce autologou s graft-versus-host disease (GVHD) after autologous bone marrow transplanta tion (ABMT). This trial was based on the results in a rodent model, in whic h cyclosporine given after ABMT induces an autoimmune syndrome tautologous GVHD) identical to allogeneic GVHD. Further, this autologous GVHD is associ ated with a graft-versus-tumor effect augmented by interferon that upregula tes MHC class II expression on normal and tumor cells, the target of the cy tolytic T cells in autologous GVHD. In this trial, cyclosporine 1 mg/kg/day was given from the day of bone marrow reinfusion until the completion of t he interferon and gamma-interferon. Gamma-interferon at 0.025 mg/m(2) every other day was started when the total white cell count was >200 cells/ml fo r 2 consecutive days and continued for a total of 10 doses after ABMT. The preparative regimens were busulfan and cyclophosphamide, or cyclophosphamid e with total body irradiation. All patients received 4HC-purged marrow graf ts. Median age was 45 years (range 19-68). The diagnoses included chemo-res istant non-Hodgkin's lymphoma (10), acute lymphoblastic leukemia (two), che mo-resistant Hodgkin's disease (two), acute myeloid leukemia tone), and mul tiple myeloma tone). Median absolute neutrophil count recovery was 25.5 day s (range 19-46 days). Median platelet count recovery was 40.5 days (range 2 8-279 days). There were nine deaths, two were related to transplant toxicit y (infection), while the other seven were due to relapse. Event-free surviv al with a median of 964 days (range 19-1441 days of follow-up was 44%. In c onclusion, treatment with cyclosporine, and gamma-interferon after ABMT was well tolerated and did not impair engraftment. Further studies with a larg er number of patients are required to document any beneficial anti-tumor ef fect of autologous GVHD induction after ABMT.