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Autografting

Second autologous transplant with cyclosporin/interferon α-induced graft versus host disease for patients who have failed first-line consolidation

Summary:

The prognosis for patients with non-Hodgkin's lymphoma (NHL) and advanced Hodgkin's disease (HD) who relapse following autologous transplant is poor. We report on a pilot study designed to evaluate the feasibility of using Cyclosporin A and interferon α to induce autologous GVHD following a second autologous transplant for relapsed lymphoma. In all, 10 patients entered the study with median age 46.5 years. Diagnosis was NHL (n=7) or Hodgkin's lymphoma (n=3). All had relapsed from a prior autologous transplant. The second transplant was well tolerated by all patients. Histological changes consistent with cutaneous GVHD developed in 30% of patients at a median of 22.5 days from transplant and settled spontaneously in all cases. Five patients have died (four from progressive disease) at a median 7 months from second transplant. Five patients are still alive and in complete remission at a median of 20 months from transplant. Median overall survival for the group is 13.5 months and median relapse-free survival has not been reached at 42 months. This is a well-tolerated regimen for use in this poor-risk group of patients with lymphoma. The overall survival and event-free survival are encouraging, however further studies are necessary.

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References

  1. Vose JM, Bierman PJ, Anderson JR et al. Progressive disease after high-dose therapy and autologous transplantation for lymphoid malignancy: clinical course and patient follow-up. Blood 1992; 80: 2142–2148.

    CAS  PubMed  Google Scholar 

  2. Shamash J, Lee SM, Radford JA et al. Patterns of relapse and subsequent management following high-dose chemotherapy with autologous haematopoietic support in relapsed or refractory Hodgkin's lymphoma: a two centre study. Ann Oncol 2000; 11: 715–719.

    Article  CAS  PubMed  Google Scholar 

  3. Vandenberghe E, Pearce R, Taghipour G et al. Role of a second transplant in the management of poor-prognosis lymphomas: a report from the European Blood and Bone Marrow Registry. J Clin Oncol 1997; 15: 1595–1600.

    Article  CAS  PubMed  Google Scholar 

  4. De Lima M, van Besien KW, Giralt SA et al. Bone marrow transplantation after failure of autologous transplant for non-Hodgkin's lymphoma. Bone Marrow Transplant 1997; 19: 121–127.

    Article  CAS  PubMed  Google Scholar 

  5. Tsai T, Goodman S, Saez R et al. Allogeneic bone marrow transplantation in patients who relapse after autologous transplantation. Bone Marrow Transplant 1997; 20: 859–863.

    Article  CAS  PubMed  Google Scholar 

  6. Jones RJ, Ambinder RF, Piantadosi S, Santos GW . Evidence of a graft-versus-lymphoma effect associated with allogeneic bone marrow transplantation. Blood 1991; 77: 649–653.

    CAS  PubMed  Google Scholar 

  7. Hood AF, Vogelsang GB, Black LP et al. Acute graft-vs-host disease. Development following autologous and syngeneic bone marrow transplantation. Arch Dermatol 1987; 123: 745–750.

    Article  CAS  PubMed  Google Scholar 

  8. Hess AD, Thoburn CJ . Immunobiology and immunotherapeutic implications of syngeneic/autologous graft-versus-host disease. Immunol Rev 1997; 157: 111–123.

    Article  CAS  PubMed  Google Scholar 

  9. Noga SJ, Horwitz L, Kim H et al. Interferon-gamma potentiates the antitumor effect of cyclosporine-induced autoimmunity. J Hematother 1992; 1: 75–84.

    Article  CAS  PubMed  Google Scholar 

  10. Horowitz MM, Gale RP, Sondel PM et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood 1990; 75: 555–562.

    CAS  PubMed  Google Scholar 

  11. Reynolds C, Ratanatharathorn V, Adams P et al. Allogeneic stem cell transplantation reduces disease progression compared to autologous transplantation in patients with multiple myeloma. Bone Marrow Transplant 2001; 27: 801–807.

    Article  CAS  PubMed  Google Scholar 

  12. Weiden PL, Flournoy N, Thomas ED et al. Antileukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts. N Engl J Med 1979; 300: 1068–1073.

    Article  CAS  PubMed  Google Scholar 

  13. Gale RP, Champlin RE . How does bone-marrow transplantation cure leukaemia? Lancet 1984; 2: 28–30.

    Article  CAS  PubMed  Google Scholar 

  14. Glazier A, Tutschka PJ, Farmer ER, Santos GW . Graft-versus-host disease in cyclosporin A-treated rats after syngeneic and autologous bone marrow reconstitution. J Exp Med 1983; 158: 1–8.

    Article  CAS  PubMed  Google Scholar 

  15. Bryson JS, Jennings CD, Caywood BE, Kaplan AM . Induction of a syngeneic graft-versus-host disease-like syndrome in DBA/2 mice. Transplantation 1989; 48: 1042–1047.

    Article  CAS  PubMed  Google Scholar 

  16. Fischer AC, Beschorner WE, Hess AD . Requirements for the induction and adoptive transfer of cyclosporine-induced syngeneic graft-versus-host disease. J Exp Med 1989; 169: 1031–1041.

    Article  CAS  PubMed  Google Scholar 

  17. Hess AD, Fischer AC, Horwitz L et al. Characterization of peripheral autoregulatory mechanisms that prevent development of cyclosporin-induced syngeneic graft-versus-host disease. J Immunol 1994; 153: 400–411.

    CAS  PubMed  Google Scholar 

  18. Shinozawa T, Beschorner WE, Hess AD . The thymus and prolonged administration of cyclosporine. Irreversible immunopathologic changes associated with autologous pseudo-graft-versus-host disease. Transplantation 1990; 50: 106–111.

    Article  CAS  PubMed  Google Scholar 

  19. Beschorner WE, Ren H, Phillips J et al. Prevention of syngeneic graft-versus-host disease by recovery of thymic microenvironment after cyclosporine. Transplantation 1991; 52: 668–674.

    Article  CAS  PubMed  Google Scholar 

  20. Hess AD, Horwitz L, Beschorner WE, Santos GW . Development of graft-vs-host disease-like syndrome in cyclosporine-treated rats after syngeneic bone marrow transplantation. I. Development of cytotoxic T lymphocytes with apparent polyclonal anti-Ia specificity, including autoreactivity. J Exp Med 1985; 161: 718–730.

    Article  CAS  PubMed  Google Scholar 

  21. Geller RB, Esa AH, Beschorner WE et al. Successful in vitro graft-versus-tumor effect against an Ia-bearing tumor using cyclosporine-induced syngeneic graft-versus-host disease in the rat. Blood 1989; 74: 1165–1171.

    CAS  PubMed  Google Scholar 

  22. Hess AD, Bright EC, Thoburn C et al. Specificity of effector T lymphocytes in autologous graft-versus-host disease: role of the major histocompatibility complex class II invariant chain peptide. Blood 1997; 89: 2203–2209.

    CAS  PubMed  Google Scholar 

  23. Bryson JS, Jennings CD, Lowery DM et al. Rejection of an MHC class II negative tumor following induction of murine syngeneic graft-versus-host disease. Bone Marrow Transplant 1999; 23: 363–372.

    Article  CAS  PubMed  Google Scholar 

  24. Miura Y, Ueda M, Zeng W H et al. Induction of autologous graft-versus-host disease with cyclosporin A after peripheral blood stem cell transplantation: analysis of factors affecting induction. J Allergy Clin Immunol 2000; 106: S51–S57.

    Article  CAS  PubMed  Google Scholar 

  25. Jones RJ, Vogelsang GB, Hess AD et al. Induction of graft-versus-host disease after autologous bone marrow transplantation. Lancet 1989; 1: 754–757.

    Article  CAS  PubMed  Google Scholar 

  26. Ratanatharathorn V, Uberti J, Karanes C et al. Phase I study of alpha-interferon augmentation of cyclosporine-induced graft versus host disease in recipients of autologous bone marrow transplantation. Bone Marrow Transplant 1994; 13: 625–630.

    CAS  PubMed  Google Scholar 

  27. Pati AR, Godder KT, Abhyankar SH et al. Cyclosporine-induced autologous graft-versus-host disease following autologous blood stem cell transplantation for lymphoma. Bone Marrow Transplant 1996; 17: 1081–1083.

    CAS  PubMed  Google Scholar 

  28. Gryn J, Johnson E, Goldman N et al. The treatment of relapsed or refractory intermediate grade non-Hodgkin's lymphoma with autologous bone marrow transplantation followed by cyclosporine and interferon. Bone Marrow Transplant 1997; 19: 221–226.

    Article  CAS  PubMed  Google Scholar 

  29. Vogelsang G, Bitton R, Piantadosi S et al. Immune modulation in autologous bone marrow transplantation: cyclosporine and gamma-interferon trial. Bone Marrow Transplant 1999; 24: 637–640.

    Article  CAS  PubMed  Google Scholar 

  30. Baron F, Gothot A, Salmon JP et al. Clinical course and predictive factors for cyclosporin-induced autologous graft-versus-host disease after autologous haematopoietic stem cell transplantation. Br J Haematol 2000; 111: 745–753.

    CAS  PubMed  Google Scholar 

  31. Miura Y, Thoburn CJ, Bright EC et al. Characterization of the T-cell repertoire in autologous graft-versus-host disease (GVHD): evidence for the involvement of antigen-driven T-cell response in the development of autologous GVHD. Blood 2001; 98: 868–876.

    Article  CAS  PubMed  Google Scholar 

  32. Wu DY, Goldschneider I . Tolerance to cyclosporin A-induced autologous graft-versus-host disease is mediated by a CD4+CD25+ subset of recent thymic emigrants. J Immunol 2001; 166: 7158–7164.

    Article  CAS  PubMed  Google Scholar 

  33. Branson K, Chopra R, Kottaridis PD et al. Role of nonmyeloablative allogeneic stem-cell transplantation after failure of autologous transplantation in patients with lymphoproliferative malignancies. J Clin Oncol 2002; 20: 4022–4031.

    Article  PubMed  Google Scholar 

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Correspondence to S A Schey.

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Streetly, M., Kazmi, M., Radia, D. et al. Second autologous transplant with cyclosporin/interferon α-induced graft versus host disease for patients who have failed first-line consolidation. Bone Marrow Transplant 33, 1131–1135 (2004). https://doi.org/10.1038/sj.bmt.1704484

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