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Summary: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 autologous graft-versus-host disease (GVHD) after autologous bone marrow transplantation (ABMT). This trial was based on the results in a rodent model, in which cyclosporine given after ABMT induces an autoimmune syndrome (autologous GVHD) identical to allogeneic GVHD. Further, this autologous GVHD is associated with a graft-versus-tumor effect augmented by interferon that upregulates MHC class II expression on normal and tumor cells, the target of the cytolytic 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 the interferon and gamma-interferon. Gamma-interferon at 0.025 mg/m 2 every other day was started when the total white cell count was Ͼ200 cells/ml for 2 consecutive days and continued for a total of 10 doses after ABMT. The preparative regimens were busulfan and cyclophosphamide, or cyclophosphamide with total body irradiation. All patients received 4HC-purged marrow grafts. Median age was 45 years (range 19-68). The diagnoses included chemo-resistant non-Hodgkin's lymphoma (10), acute lymphoblastic leukemia (two), chemo-resistant Hodgkin's disease (two), acute myeloid leukemia (one), and multiple myeloma (one). Median absolute neutrophil count recovery was 25.5 days (range 19-46 days). Median platelet count recovery was 40.5 days (range 28-279 days). There were nine deaths, two were related to transplant toxicity (infection), while the other seven were due to relapse. Event-free survival with a median of 964 days (range 19-1441 days of follow-up was 44%. In conclusion, treatment with cyclosporine, and gammainterferon after ABMT was well tolerated and did not impair engraftment. Further studies with a larger number of patients are required to document any beneficial anti-tumor effect of autologous GVHD induction after ABMT.

In order to test the effect of peripheral blood mononuclear cell infusions on hematopoietic recovery in man we intensively leukapheresed a normal identical twin and obtained 9.8 x 10(10) peripheral blood mononuclear cells containing 4 x 10(5) CFU-C. These isologous cells were infused into his identical twin brother who had received 150 rad of total body irradiation and intensive combination chemotherapy as adjuvant therapy for Ewing's sarcoma. When compared to other patients receiving similar treatment, leukocyte recovery was accelerated by 3–4 wk, and occurred at a rate comparable to that induced by infusion of autologous cryopreserved marrow. Recovery of granulocytes, monocytes and platelets was not accelerated. The low number of CFU-C present in the preparation used ((one-eighth the number of CFU-C we usually obtain from bone marrow autograft collections) may have led to the pattern of hematopoietic recovery we observed in this patient.

In order to test the effect of peripheral blood mononuclear cell infusions on hematopoietic recovery in man we intensively leukapheresed a normal identical twin and obtained 9.8 x 10(10) peripheral blood mononuclear cells containing 4 x 10(5) CFU-C. These isologous cells were infused into his identical twin brother who had received 150 rad of total body irradiation and intensive combination chemotherapy as adjuvant therapy for Ewing's sarcoma. When compared to other patients receiving similar treatment, leukocyte recovery was accelerated by 3–4 wk, and occurred at a rate comparable to that induced by infusion of autologous cryopreserved marrow. Recovery of granulocytes, monocytes and platelets was not accelerated. The low number of CFU-C present in the preparation used ((one-eighth the number of CFU-C we usually obtain from bone marrow autograft collections) may have led to the pattern of hematopoietic recovery we observed in this patient.

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