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

G. B. Vogelsang, R. J. Bitton, S. Piantadosi, V. Altomonte, T. Horn, R. J. Jones, C. Miller, D. Marcellus, R. Abrams, A. D. Hess

Research output: Contribution to journalArticle

Abstract

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 tautologous GVHD) identical to allogeneic GVKD. 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.

Original languageEnglish (US)
Pages (from-to)637-640
Number of pages4
JournalBone marrow transplantation
Volume24
Issue number6
DOIs
StatePublished - Jan 1 1999

Keywords

  • Autologous GVHD
  • Autologous transplant
  • Cyclosporine
  • Gamma interferon

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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    Vogelsang, G. B., Bitton, R. J., Piantadosi, S., Altomonte, V., Horn, T., Jones, R. J., Miller, C., Marcellus, D., Abrams, R., & Hess, A. D. (1999). Immune modulation in autologous bone marrow transplantation: Cyclosporine and gamma-interferon trial. Bone marrow transplantation, 24(6), 637-640. https://doi.org/10.1038/sj.bmt.1701942