Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Conditioning Regimens

Fludarabine, cyclophosphamide plus thymoglobulin conditioning regimen for unrelated bone marrow transplantation in severe aplastic anemia

Summary:

Antithymocyte globulin (ATG) has been used in severe aplastic anemia (SAA) as a part of the conditioning regimen. Among the many kinds of ATG preparations, thymoglobulin had been found to be more effective in preventing GVHD and rejection of organ transplants. As the fludarabine-based conditioning regimens without total body irradiation have been reported to be promising for bone marrow transplantation (BMT) from alternative donors in SAA, thymoglobulin was added to fludarabine and cyclophosphamide conditioning to reduce GVHD and to allow good engraftment in unrelated BMT. Five patients underwent BMT with cyclophosphamide (50 mg/kg once daily i.v. on days −9, −8, −7 and −6), fludarabine (30 mg/m2 once daily i.v. on days −5, −4, −3 and −2) and thymoglobulin (2.5 mg/kg once daily i.v. on days −3, −2 and −1) from HLA-matched unrelated donors. Complete donor type hematologic recovery was achieved in all patients. No serious complication occurred during BMT. Only one patient developed grade I acute GVHD resolved spontaneously. Except for one who had rupture of hepatic adenoma 78 days after BMT, all the other four patients are still alive with median 566 days. Fludarabine, cyclophosphamide plus thymoglobulin conditioning allows for the promising results of good engraftment, tolerable toxicity and minimal GVHD.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Storb R, Etzioni 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.

    CAS  PubMed  Google Scholar 

  2. Georges GE, Storb R . Allogeneic hematopoietic cell transplantation for aplastic anemia. In: Blume KG, Forman SJ, Appelbaum FR (eds) Thomas' Hematopoietic Cell Transplantation. Blackwell Publishing Ltd: Oxford, 2004; pp 981–1001.

    Google Scholar 

  3. Deeg HJ, Anasetti C, Petersdorf E et al. Cyclophosphamide plus ATG conditioning is insufficient for sustained hematopoietic reconstitution in patients with severe aplastic anemia transplanted with marrow from HLA-A, B, DRB matched unrelated donors. Blood 1994; 83: 3417–3418.

    CAS  PubMed  Google Scholar 

  4. Deeg HJ, Amylon ID, Harris RE et al. Marrow transplants from unrelated donors for patients with aplastic anemia: minimum effective dose of total body irradiation. Biol Blood Marrow Transplant 2001; 7: 208–215.

    Article  CAS  PubMed  Google Scholar 

  5. Kojima S, Inaba J, Yoshimi A et al. Unrelated donor marrow transplantation in children with severe aplastic anaemia using cyclophosphamide, anti-thymocyte globulin and total body irradiation. Br J Haematol 2001; 114: 706–711.

    Article  CAS  PubMed  Google Scholar 

  6. Vassiliou GS, Webb DK, Pamphilon D et al. Improved outcome of alternative donor bone marrow transplantation in children with severe aplastic anaemia using a conditioning regimen containing low-dose total body irradiation, cyclophosphamide and Campath. Br J Haematol 2001; 114: 701–705.

    Article  CAS  PubMed  Google Scholar 

  7. Chan KW, Li CK, Worth LL et al. A fludarabine-based conditioning regimen for severe aplastic anemia. Bone Marrow Transplant 2001; 27: 125–128.

    Article  CAS  PubMed  Google Scholar 

  8. Horstmann M, Stockschlader M, Kruger W et al. Cyclophosphamide/antithymocyte globulin conditioning of patients with severe aplastic anemia for marrow transplantation from HLA-matched siblings: preliminary results. Ann Hematol 1995; 71: 77–81.

    Article  CAS  PubMed  Google Scholar 

  9. Zander AR, Zabelina T, Kroger N et al. Use of a five-agent GVHD prevention regimen in recipients of unrelated donor marrow. Bone Marrow Transplant 1999; 23: 889–893.

    Article  CAS  PubMed  Google Scholar 

  10. Kroger N, Zabelina T, Kruger W et al. Anti-thymocyte-globulin as part of the preparative regimen prevents graft failure and severe graft versus host disease (GvHD) in allogeneic stem cell transplantation from unrelated donors. Ann Hematol 2001; 80: 209–215.

    Article  CAS  PubMed  Google Scholar 

  11. Bacigalupo A, Lamparelli T, Bruzzi P et al. Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO). Blood 2001; 98: 2942–2947.

    Article  CAS  PubMed  Google Scholar 

  12. Bacigalupo A, Oneto R, Lamparelli T et al. Pre-emptive treatment of acute graft versus host disease in alternative donor transplants: a randomized trial of day+7 rabbit anti-thymocyte globulin (ATG). Blood 2002; 100: 637a.

    Google Scholar 

  13. Remberger M, Storer B, Ringden O, Anasetti C . Association between pretransplant thymoglobulin and reduced non-relapse mortality rate after marrow transplantation from unrelated donors. Bone Marrow Transplant 2002; 29: 391–397.

    Article  CAS  PubMed  Google Scholar 

  14. Bonifazi F, Bandini G, Rondelli D et al. Reduced incidence of GVHD without increase in relapse with low-dose rabbit ATG in the preparative regimen for unrelated bone marrow transplants in CML. Bone Marrow Transplant 2003; 32: 237–242.

    Article  CAS  PubMed  Google Scholar 

  15. Finke J, Schmoor C, Lang H et al. Matched and mismatched allogeneic stem-cell transplantation from unrelated donors using combined graft-versus-host disease prophylaxis including rabbit anti-T lymphocyte globulin. J Clin Oncol 2003; 21: 506–513.

    Article  PubMed  Google Scholar 

  16. Zuckermann AO, Grimm M, Czerny M et al. Improved long-term results with thymoglobuline induction therapy after cardiac transplantation: a comparison of two different rabbit-antithymocyte globulines. Transplantation 2000; 69: 1890–1898.

    Article  CAS  PubMed  Google Scholar 

  17. Brennan DC, Flavin K, Lowell JA et al. A randomized, double-blinded comparison of thymoglobulin versus Atgam for induction immunosuppressive therapy in adult renal transplant recipients. Transplantation 1999; 67: 1011–1018.

    Article  CAS  PubMed  Google Scholar 

  18. Remberger M, Svahn BM, Hentschke P et al. Effect on cytokine release and graft-versus-host disease of different anti-T cell antibodies during conditioning for unrelated haematopoietic stem cell transplantation. Bone Marrow Transplant 1999; 24: 823–830.

    Article  CAS  PubMed  Google Scholar 

  19. Kang HJ, Shin HY, Choi HS et al. Autologous peripheral blood stem cell transplantation with BCVAC conditioning in childhood acute myeloid leukemia. Bone Marrow Transplant 2004; 33: 471–476.

    Article  CAS  PubMed  Google Scholar 

  20. Common Toxicity Criteria Version 2.0. National Cancer Institute: Bethesda, MD, 1999.

  21. Comans-Bitter WM, de Groot R, van den Beemd R et al. Immunophenotyping of blood lymphocytes in childhood. Reference values for lymphocyte subpopulations. J Pediatr 1997; 130: 388–393.

    Article  CAS  PubMed  Google Scholar 

  22. Sanders JE . Chronic graft-versus-host disease and late effects after hematopoietic stem cell transplantation. Int J Hematol 2002; 76 (Suppl 2): 15–28.

    Article  PubMed  Google Scholar 

  23. Socie 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.

    CAS  PubMed  Google Scholar 

  24. Michallet MC, Saltel F, Preville X et al. Cathepsin-B-dependent apoptosis triggered by antithymocyte globulins: a novel mechanism of T-cell depletion. Blood 2003; 102: 3719–3726.

    Article  CAS  PubMed  Google Scholar 

  25. Genestier L, Fournel S, Flacher M et al. Induction of Fas (Apo-1, CD95)-mediated apoptosis of activated lymphocytes by polyclonal antithymocyte globulins. Blood 1998; 91: 2360–2368.

    CAS  PubMed  Google Scholar 

  26. Chao NJ, Schmidt GM, Niland JC et al. Cyclosporine, methotrexate, and prednisone compared with cyclosporine and prednisone for prophylaxis of acute graft-versus-host disease. N Engl J Med 1993; 329: 1225–1230.

    Article  CAS  PubMed  Google Scholar 

  27. Kim DH, Kim JG, Sohn SK et al. Clinical impact of early absolute lymphocyte count after allogeneic stem cell transplantation. Br J Haematol 2004; 125: 217–224.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to H Y Shin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kang, H., Shin, H., Choi, H. et al. Fludarabine, cyclophosphamide plus thymoglobulin conditioning regimen for unrelated bone marrow transplantation in severe aplastic anemia. Bone Marrow Transplant 34, 939–943 (2004). https://doi.org/10.1038/sj.bmt.1704720

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704720

Keywords

This article is cited by

Search

Quick links