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:

Post-Transplant Events

Non-radiotherapy conditioning with stem cell transplantation from alternative donors in children with refractory severe aplastic anemia

Summary:

Conditioning including total body/lymphoid irradiation is widely used to prevent graft rejection in patients with refractory severe aplastic anemia (SAA) undergoing hemopoietic cell transplantation (HCT) from alternative donors and or after graft manipulation. To reduce regimen-related toxicity we transplanted three children with refractory SAA after conditioning with radiotherapy-free regimens. Conditioning included fludarabine 175–180 mg/m2 in all patients. In addition, patient 1 (failing two previous grafts) received thiotepa 10 mg/kg and Campath-1H 60 mg/m2; patient 2 cyclophosphamide 120 mg/kg, thiotepa 15 mg/kg and OKT-3 0.1 mg/kg/day for 4 weeks; and patient 3 cyclophosphamide 120 and ATG 90 mg/kg. Stem cell source was unmanipulated marrow from the same unrelated donor as for the two previous transplantations in patient 1 and CD34+-purified peripheral blood stem cells from an HLA-matched unrelated donor and from the haploidentical mother in patients 2 and 3. Only patient 1 received graft-versus-host disease (GVHD) prophylaxis with cyclosporine A and mycophenolate mofetil. Follow-up is now 30, 51, and 15 months. None of the patients developed GVHD. All patients have normal counts with complete donor chimerism. Fludarabine-based conditioning is powerfully immunosuppressive and may be used for children with refractory SAA undergoing HCT from alternative donors even after rejection following previous HCT.

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. 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: 504–514.

    CAS  Google Scholar 

  2. Doney K, Leisenring W, Storb R, Appelbaum FR . Primary treatment of acquired aplastic anemia: outcomes with bone marrow transplantation and immunosuppressive therapy. Seattle Bone Marrow Transplant Team. Ann Intern Med 1997; 126: 107–115.

    Article  CAS  Google Scholar 

  3. 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  Google Scholar 

  4. Kojima S, Matsuyama T, Kato S et al. Outcome of 154 patients with severe aplastic anemia who received transplants from unrelated donors: the Japan Marrow Donor Program. Blood 2002; 100: 799–803.

    Article  CAS  Google Scholar 

  5. 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.

    CAS  Google Scholar 

  6. Deeg HJ, Seidel K, Casper J et al. Marrow transplantation from unrelated donors for patients with severe aplastic anemia who have failed immunosuppressive therapy. Biol Blood Marrow Transplant 1999; 5: 243–252.

    Article  CAS  Google Scholar 

  7. Bacigalupo A, Oneto R, Bruno B et al. Current results of bone marrow transplantation in patients with acquired severe aplastic anemia. Report of the European Group for Blood and Marrow transplantation. On behalf of the Working Party on Severe Aplastic Anemia of the European Group for Blood and Marrow Transplantation. Acta Haematol 2000; 103: 19–25.

    Article  CAS  Google Scholar 

  8. Gustafsson A, Remberger M, Winiarski J, Ringden O . Unrelated bone marrow transplantation in children: outcome and a comparison with sibling donor grafting. Bone Marrow Transplant 2000; 25: 1059–1065.

    Article  CAS  Google Scholar 

  9. Leung WH, Turner V, Richardson SL et al. Effect of HLA class I or class II incompatibility in pediatric marrow transplantation from unrelated and related donors. Hum Immunol 2001; 62: 399–407.

    Article  CAS  Google Scholar 

  10. Balduzzi A, Gooley T, Anasetti C et al. Unrelated donor marrow transplantation in children. Blood 1995; 86: 3247–3256.

    CAS  Google Scholar 

  11. Sasazuki T, Juji T, Morishima Y et al. Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor. Japan Marrow Donor Program. N Engl J Med 1998; 339: 1177–1185.

    Article  CAS  Google Scholar 

  12. Champlin RE, Horowitz MM, van Bekkum DW et al. Graft failure following bone marrow transplantation for severe aplastic anemia: risk factors and treatment results. Blood 1989; 73: 606–613.

    CAS  Google Scholar 

  13. Benesch M, Urban C, Sykora KW et al. Transplantation of highly purified CD34+ progenitor cells from alternative donors in children with refractory severe aplastic anaemia. Br J Haematol 2004; 125: 58–63.

    Article  Google Scholar 

  14. Schwinger W, Urban C, Lackner H et al. Unrelated peripheral blood stem cell transplantation with ‘megadoses’ of purified CD34+ cells in three children with refractory severe aplastic anemia. Bone Marrow Transplant 2000; 25: 513–517.

    Article  CAS  Google Scholar 

  15. Führer M, Burdach S, Ebell W et al. Relapse and clonal disease in children with aplastic anemia (AA) after immunosuppressive therapy (IST): the SAA 94 experience. German/Austrian Pediatric Aplastic Anemia Working Group. Klin Pädiatr 1998; 210: 173–179.

    Article  Google Scholar 

  16. Bensinger WI . High-dose chemotherapy and chemoradiotherapy preparative regimens. In: Atkinson K, Champlin R, Ritz J, Fibbe WE, Ljungman P, Brenner MK (eds). Clinical Bone Marrow and Blood Stem Cell Transplantation, 3rd edn. Cambridge University Press: UK, pp 337–356.

  17. 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 Hematol 2001; 114: 701–705.

    Article  CAS  Google Scholar 

  18. Kojima S, Horibe K, Inaba J et al. Long-term outcome of acquired aplastic anaemia in children: comparison between immunosuppressive therapy and bone marrow transplantation. Br J Hematol 2000; 111: 321–328.

    Article  CAS  Google Scholar 

  19. Friedman DL, Leisenring W, Schwartz JL, Deeg HJ . Second malignant neoplasms following hematopoietic stem cell transplantation. Int J Hematol 2004; 79: 229–234.

    Article  Google Scholar 

  20. Leiper AD . Non-endocrine late complications of bone marrow transplantation in childhood: part I. Br J Hematol 2002; 118: 3–22.

    Article  Google Scholar 

  21. Leiper AD . Non-endocrine late complications of bone marrow transplantation in childhood: Part II. Br J Hematol 2002; 118: 23–43.

    Article  Google Scholar 

  22. Sanders JE . Endocrine complications of high-dose therapy with stem cell transplantation. Pediatr Transplant 2004; 8 (Suppl. 5): 39–50.

    Article  Google Scholar 

  23. 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  Google Scholar 

  24. Jackson GH . Use of fludarabine in the treatment of acute myeloid leukemia. Hematol J 2004; 5 (Suppl. 1): 62–67.

    Article  Google Scholar 

  25. Nabhan C, Gartenhaus RB, Tallman MS . Purine nucleoside analogues and combination therapies in B-cell chronic lymphocytic leukemia: dawn of a new era. Leuk Res 2004; 28: 429–442.

    Article  CAS  Google Scholar 

  26. Maris MB, Niederwieser D, Sandmaier BM et al. HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies. Blood 2003; 102: 2021–2030.

    Article  CAS  Google Scholar 

  27. Storb R . Non-myeloablative allogeneic transplantation-state-of-the-art. Pediatr Transplant 2004; 8 (Suppl. 5): 12–18.

    Article  Google Scholar 

  28. Aversa F, Tabilio A, Velardi A et al. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med 1998; 339: 1186–1193.

    Article  CAS  Google Scholar 

  29. Jacobsohn DA, Duerst R, Tse W, Kletzel M . Reduced intensity haemopoietic stem-cell transplantation for treatment of non-malignant diseases in children. Lancet 2004; 364: 156–162.

    Article  Google Scholar 

  30. Claviez A, Klingebiel T, Beyer J et al. Allogeneic peripheral blood stem cell transplantation following fludarabine-based conditioning in six children with advanced Hodgkin's disease. Ann Hematol 2004; 83: 237–241.

    Article  Google Scholar 

  31. 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  Google Scholar 

  32. Del Toro G, Satwani P, Harrison L et al. A pilot study of reduced intensity conditioning and allogeneic stem cell transplantation from unrelated cord blood and matched family donors in children and adolescent recipients. Bone Marrow Transplant 2004; 33: 613–622.

    Article  CAS  Google Scholar 

  33. de la Fuente J, Reiss S, McCloy M et al. Non-TBI stem cell transplantation protocol for Fanconi anaemia using HLA-compatible sibling and unrelated donors. Bone Marrow Transplant 2003; 32: 653–656.

    Article  CAS  Google Scholar 

  34. Langer T, Beck JD, Gravou-Apostulatou C et al. Successful treatment of primary refractory acute myeloid leukemia with megadose stem cell transplantation, bone marrow boost and reduced intensity conditioning avoiding chronic graft vs host disease and severe late toxicity. Pediatr Transplant 2003; 7: 494–496.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M Benesch.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Urban, C., Benesch, M., Sykora, K. et al. Non-radiotherapy conditioning with stem cell transplantation from alternative donors in children with refractory severe aplastic anemia. Bone Marrow Transplant 35, 591–594 (2005). https://doi.org/10.1038/sj.bmt.1704792

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704792

Keywords

This article is cited by

Search

Quick links