Seminars in Hematology
Volume 37, Issue 1 , Pages 69-80 , January 2000

Treatment of acquired severe aplastic anemia: Bone marrow transplantation compared with immunosuppressive therapy-the European group for blood and marrow transplantation experience

  • Andrea Bacigalupo

      Affiliations

    • Corresponding Author InformationAddress reprint requests to A. Bacigalupo, MD, Department of Hematology, Ospedak San Martina, Genova, Italy 16132.
    • From the Working Party on Severe Aplastic Anemia of the European Blood and Marrow Transplantation Group, Leiden, The Netherlands
    • From the Medical Statistical Department, University of Leiden, Leiden, The Netherlands
    • ,
  • Ronald Brand

      Affiliations

    • From the Working Party on Severe Aplastic Anemia of the European Blood and Marrow Transplantation Group, Leiden, The Netherlands
    • From the Medical Statistical Department, University of Leiden, Leiden, The Netherlands
    • ,
  • Rosi Oneto

      Affiliations

    • From the Working Party on Severe Aplastic Anemia of the European Blood and Marrow Transplantation Group, Leiden, The Netherlands
    • From the Medical Statistical Department, University of Leiden, Leiden, The Netherlands
    • ,
  • Barbara Bruno

      Affiliations

    • From the Working Party on Severe Aplastic Anemia of the European Blood and Marrow Transplantation Group, Leiden, The Netherlands
    • From the Medical Statistical Department, University of Leiden, Leiden, The Netherlands
    • ,
  • Gerard Sodé

      Affiliations

    • From the Working Party on Severe Aplastic Anemia of the European Blood and Marrow Transplantation Group, Leiden, The Netherlands
    • From the Medical Statistical Department, University of Leiden, Leiden, The Netherlands
    • ,
  • Jakob Passweg

      Affiliations

    • From the Working Party on Severe Aplastic Anemia of the European Blood and Marrow Transplantation Group, Leiden, The Netherlands
    • From the Medical Statistical Department, University of Leiden, Leiden, The Netherlands
    • ,
  • Anna Locasciulli

      Affiliations

    • From the Working Party on Severe Aplastic Anemia of the European Blood and Marrow Transplantation Group, Leiden, The Netherlands
    • From the Medical Statistical Department, University of Leiden, Leiden, The Netherlands
    • ,
  • Maria Teresa Van Lint

      Affiliations

    • From the Working Party on Severe Aplastic Anemia of the European Blood and Marrow Transplantation Group, Leiden, The Netherlands
    • From the Medical Statistical Department, University of Leiden, Leiden, The Netherlands
    • ,
  • André Tichelli

      Affiliations

    • From the Working Party on Severe Aplastic Anemia of the European Blood and Marrow Transplantation Group, Leiden, The Netherlands
    • From the Medical Statistical Department, University of Leiden, Leiden, The Netherlands
    • ,
  • Shaun McCann

      Affiliations

    • From the Working Party on Severe Aplastic Anemia of the European Blood and Marrow Transplantation Group, Leiden, The Netherlands
    • From the Medical Statistical Department, University of Leiden, Leiden, The Netherlands
    • ,
  • Judith Marsh

      Affiliations

    • From the Working Party on Severe Aplastic Anemia of the European Blood and Marrow Transplantation Group, Leiden, The Netherlands
    • From the Medical Statistical Department, University of Leiden, Leiden, The Netherlands
    • ,
  • Per Ljungman

      Affiliations

    • From the Working Party on Severe Aplastic Anemia of the European Blood and Marrow Transplantation Group, Leiden, The Netherlands
    • From the Medical Statistical Department, University of Leiden, Leiden, The Netherlands
    • ,
  • Jill Hows

      Affiliations

    • From the Working Party on Severe Aplastic Anemia of the European Blood and Marrow Transplantation Group, Leiden, The Netherlands
    • From the Medical Statistical Department, University of Leiden, Leiden, The Netherlands
    • ,
  • Pedro Marin

      Affiliations

    • From the Working Party on Severe Aplastic Anemia of the European Blood and Marrow Transplantation Group, Leiden, The Netherlands
    • From the Medical Statistical Department, University of Leiden, Leiden, The Netherlands
    • ,
  • Hubert Schrezenmeier

      Affiliations

    • From the Working Party on Severe Aplastic Anemia of the European Blood and Marrow Transplantation Group, Leiden, The Netherlands
    • From the Medical Statistical Department, University of Leiden, Leiden, The Netherlands

References 

  1. Ascensao J, Kagan W, Moore M, et al.  Aplastic anemia: Evidence for an immunological mechanism. Lancet. 1976;1:669–671
  2. Bacigalupo A, Hows J, Gluckman E, et al.  Bone marrow transplantation (BMT) versus immunosuppression for the treatment of severe aplastic anaemia (SAA): A report of the EBMT SAA Working Party. Br J Haematol. 1988;177:70–74
  3. Bacigalupo A, Chaple M, Hows J, et al.  Treatment of aplastic anemia (AA) with antilymphocyte globulin (ALG) and methylprednisolone (MPred) with or without androgens: A randomized trial from the EBMT SAA working party. Br J Haematol. 1993;83:145–151
  4. Bacigalupo A, Broccia G, Corda G, et al.  Antilymphocyte globulin, cyclosporin and granulocyte stimulating factor in patients with acquired severe aplastic anemia (SAA): A pilot study of the EBMT SAA working party. Blood. 1995;85:1348–1353
  5. Bayever E, Champlin R, Ho W, et al.  Comparison between bone marrow transplantation and antithymocyte globulin in treatment of young patients with severe aplastic anemia. J Pediatr. 1984;105:920–925
  6. Brodsky RA, Sensenbrenner LL, Jones RJ. Complete remission in severe aplastic anemia after high-dose cyclophosphamide without bone marrow transplantation. Blood. 1998;87:491–494
  7. Camitta BM, Thomas ED, Nathan DG, et al.  A prospective study of androgens and bone marrow transplantation for treatment of severe aplastic anemia. Blood. 1979;53:504
  8. Camitta B, O'Reilly RJ, Sensenbrenner L, et al.  Antithoracic duct lymphocyte globulin therapy of severe aplastic anemia. Blood. 1983;62:883–888
  9. Champlin R, Ho W, Gale RP. Antithymocyte globulin treatment in patients with aplastic anemia: A prospective randomized trial. N Engl J Med. 1983;308:113–118
  10. Champlin RE, Ho WG, Nimer SD, et al.  Bone Marrow transplantation for severe aplastic anemia. Transplantation. 1990;49:720–724
  11. Deeg HJ, Leisenring W, Storb R, et al.  Long term outcome after marrow transplantation for severe aplastic anemia. Blood. 1998;91:3637–3645
  12. Doney K, Martin P, Storb R, et al.  A randomized trial of antihuman thymocyte globulin versus murine monoclonal antihuman T-cell antibodies as immunosuppressive therapy for aplastic anemia. Exp Hematol. 1985;13:520–524
  13. Doney K, Kopecky K, Storb R, et al.  Long-term comparison of immunosuppressive dierapy with antithymocyte globulin to bone marrow transplantation in aplastic anemia. In:  Shahidi NT editors. Aplastic Anemia and Other Bone Marrow Failure Syndromes. 1990;p. 104–114
  14. Doney K, Leisenring W, Storb R, et al.  Primary treatment of acquired aplastic anemia: Outcomes with bone marrow transplantation and immunosuppressive therapy. Ann Intern Med. 1997;126:107–115
  15. Faille A, Barrett AJ, Balitrand N, et al.  Effect of antilymphocyte globulin on granulocyte precursors in aplastic anemia. Br J Haematol. 1979;42:371–380
  16. Frickhofen N, Kaltwasser JP, Schrezenmeier H, et al.  Treatment of aplastic anemia with antithymocyte globulin and methylprednisolone with or without cyclosporine. N Engl J Med. 1991;324:1297–1304
  17. Fuhrer M, Rampf U, Burdach S, et al.  Immunosuppressive therapy (IST) and bone marrow transplantation (BMT) for aplastic anemia (AA) in children. Blood. 1998;92(suppl 1):156a; abstr 631
  18. Gluckman E, Devergie A, Poros A, Degoulet P. Results of immunosuppression in 170 cases of severe aplastic anaemia. Report of the European Group of Bone Marrow Transplant (EGBMT). Br J Haematol. 1982;51:541–550
  19. Gluckman E, Sociè G, Devergie A, et al.  Bone marrow transplantation in 107 patients with severe aplastic anemia using cyclophosphamide and thoraco-abdominal irradiation for conditioning: long-term follow-up. Blood. 1991;78:2451–2455
  20. Goldberg MA, Antin JH, Guinan EC, et al.  Cyclophosphamide cardiotoxicity: An analysis of dosing as a risk factor. Blood. 1986;68:1114–1148
  21. Haak HL, Speck B. Inhibition of CFUE and BFUE by mononuclear peripheral blood cells during chronic benzene treatment in rabbits. Acta Haematol. 1982;67:27–33
  22. Halperlin DS, Grisaru D, Freedman MH, et al.  Severe acquired aplastic anemia in children: 11-year experience with bone marrow transplantation and immunosuppressive therapy. Am J Pediatr Hematol Oncol. 1989;11:304–309
  23. Locasciulli A, Bacigalupo A, Van Lint MT, et al.  Hepatitis B virus (HBV) infection and liver disease after allogeneic bone marrow transplantation: A report of 30 cases. Bone Marrow Transplant. 1990;6:25–29
  24. Marsh JCW, Hows J, Bryett KA, et al.  Survival after antilymphocyte globulin therapy for aplastic anemia depends on disease severity. Blood. 1987;70:1046–1052
  25. Marsh J, Schrezenmeier H, Marin P, et al.  Prospective randomized multicenter study comparing cyclosporin alone versus the combination of antithymocyte globulin and cyclosporin for treatment of patients with nonsevere aplastic anemia. Blood. 1999;93:2191–2195
  26. Mathè G, Amiel JL, Schwarzenberg L, et al.  Bone marrow graft in man after conditioning by antilymphocytic serum. Br Med J. 1970;2:131–136
  27. McCann SR, Lawler M. Mixed chimaerism; detection and significance following BMT. Bone Marrow Transplant. 1993;11:91–94
  28. McCann SR, Bacigalupo A, Gluckman E, et al.  Graft rejection and second bone marrow transplants for acquired aplastic anaemia: A report from the Aplastic Anaemia Working Party of the European Bone Marrow Transplant Group. Bone Marrow Transplant. 1994;13:233–237
  29. McGlave PB, Haake R, Miller W, et al.  Therapy of severe aplastic anemia in young adults and children with allogeneic bone marrow transplantation. Blood. 1987;70:1325–1330
  30. Moore MAS, Castro-Malaspina H. Immunosuppression in aplastic anemia. Postponing the inevitable?. N Engl J Med. 1991;324:1358–1360
  31. Paquette RL, Tebyani N, Frane M, et al.  Long-term outcome of aplastic anemia in adults treated with antithymocyte globulin: Comparison with bone marrow transplantation. Blood. 1995;85:283–290
  32. Passweg JR, Sociè G, Hinterberger W, et al.  Bone marrow transplantation for severe aplastic anemia: Has outcome improved?. Blood. 1997;90:858–864
  33. Rosenfeld S, Kimball J, Vining D, et al.  Intensive immuno-suppression with antithymocyte globulin and cyclosporin as treatment for severe aplastic anemia. Blood. 1995;85:3058–3065
  34. Santos GW, Owens AH. Allogeneic marrow transplants in cyclophosphamide treated mice. Transplant Proc. 1969;1:44–46
  35. Schrezenmeier H, Marin P, Ragavachar A, et al.  Relapse of aplastic anaemia after immunosuppressive treatment: A report from the European Bone Marrow Transplantation Group SAA Working Party. Br J Haematol. 1993;85:371–377
  36. Sociè G, Henry-Amar M, Cosset JM, et al.  Increased incidence of solid malignant tumors after bone marrow transplantation for severe aplastic anemia. Blood. 1991;78:277–279
  37. Sociè G, Amar MH, Bacigalupo A, et al.  Malignancies occurring after treatment of aplastic anemia: A survey conducted by the severe aplastic anaemia Working Party of the European Group for Bone Marrow Transplantation. N Engl J Med. 1993;329:1152–1157
  38. Speck B, Gluckman E, Haak HL, et al.  Treatment of aplastic anemia by antilymphocyte globulin with and without allogeneic bone marrow infusion. Lancet. 1977;2:1145–1147
  39. Speck B, Grathwohl A, Nissen C, et al.  Treatment of severe aplastic anemia with antilymphocyte globulin or bone-marrow transplantation. Br Med J. 1981;282:860–863
  40. Speck B, Tichelli A, Grathwohl A, et al.  Treatment of severe aplastic anemia: A 12-year follow-up of patients after bone marrow transplantation or after therapy with antilymphocyte globulin. In:  Shahidi T editors. Aplastic Anemia and Other Bone Marrow Failure Syndromes. 1990;p. 96
  41. Storb R, Thomas ED, Buckner CD, et al.  Allogeneic marrow grafting for treatment of aplastic anemia: A follow up on long-term survivors. Blood. 1976;48:817–841
  42. Storb R, Prentice RL, Thomas ED. Marrow transplantation for treatment of aplastic anemia. An analysis of factors associated with graft rejection. N Engl J Med. 1977;296:61–65
  43. Storb R, Thomas ED. Marrow transplantation for treatment of aplastic anemia. Clin Haematol. 1978;7:597–609
  44. Storb R, Erzioni R, Anasetti C, et al.  Cyclophosphamide combined with antithymocyte globulin in preparation for allogeneic marrow transplants in patients with aplastic anemia. Blood. 1994;84:941–949
  45. Tichelli A, Sociè G, Henry-Amar M, et al.  Effectiveness of immunosuppressive therapy in older patients with aplastic anemia. Ann Intern Med. 1999;130:193–201
  46. Young N, Barrett J. The treatment of severe acquired aplastic anemia. Blood. 1998;85:3367–3377

☆ Supported by BIOMED EEC Grant No. 951031 to U.S., an Assodazione Italiana Ricerca contro il Cancro (AIRC) Milano grant to A.B., and by the Assodazione Ricerca Trapianto Midollo Osseo (ARITMO), Geneva.

PII: S0037-1963(00)90031-3

Seminars in Hematology
Volume 37, Issue 1 , Pages 69-80 , January 2000

Article Tools