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 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/m2 every other day was started when the total white cell count was >200 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 gamma-interferon 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.
Vogelsang
G
G
Bone Marrow Transplantation Unit of The Johns Hopkins Oncology Center, The Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Bitton
R
R
Piantadosi
S
S
Altomonte
V
V
Horn
T
T
Jones
R
R
Miller
C
C
Marcellus
D
D
Abrams
R
R
Hess
A
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000401:mortality; D016572:Cyclosporine / Q000009:adverse effects*; D006086:Graft vs Host Disease / Q000209:etiology; D006801:Humans; D007371:Interferon-gamma / Q000009:adverse effects*; D008875:Middle Aged; D011446:Prospective Studies; D014182:Transplantation, Autologous
D007371:Interferon-gamma; D016572:Cyclosporine