Skip to main content
SpringerLink
Log in

Stem Cell Transplantation for Aplastic Anemia

  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

Survival of patients with aplastic anemia treated with transplantation of bone marrow has improved significantly over the past several decades.Allogeneic bone marrow transplantation (BMT) for patients with HLA-identical siblings is now the firstline therapy, and long-term survival of approximately 90% can be expected with cyclophosphamide/antithymocyte globulin conditioning and postgrafting methotrexate/cyclosporine immunosuppression.The outcome of unrelated donor BMT has also improved significantly with the identification of a preparative regimen with less toxicity combined with the development of high-resolution DNA-based HLA typing to identify the optimal unrelated marrow donor. Patients with fully HLA-matched unrelated donors should be considered candidates for transplantation prior to exposure to repeat courses of immunosuppres-sion. Future progress in hematopoietic stem cell transplantation for aplastic anemia will be directed toward further decreasing the acute toxicity and decreasing the delayed effects of the conditioning regimens while maintaining highly reliable rates of sustained engraftment with prevention of acute and chronic graft-versus-host disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Referencess

  1. Lum LG, Seigneuret MC, Doney KC, Storb R. In vitro immuno-globulin production, proliferation, and cell markers before and after antithymocyte globulin therapy in patients with aplastic anemia.Am J Hematol. 1987;26:1–15.

    Article  PubMed  CAS  Google Scholar 

  2. Elfenbein GJ, Kallman CH, Tutschka PJ, et al. The immune system in 40 aplastic anemia patients receiving conventional therapy.Blood. 1979;53:652–665.

    PubMed  CAS  Google Scholar 

  3. Storb R, Yu C, Wagner JL, et al. Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation.Blood. 1997;89:3048–3054.

    PubMed  CAS  Google Scholar 

  4. Santos GW, Owens AH Jr. Allogeneic marrow transplants in cyclophosphamide treated mice.Transplant Proc. 1969;1:44–46.

    PubMed  CAS  Google Scholar 

  5. Storb R, Epstein RB, Rudolph RH, Thomas ED. Allogeneic canine bone marrow transplantation following cyclophosphamide.Transplantation. 1969;7:378–386.

    Article  PubMed  CAS  Google Scholar 

  6. Thomas ED, Buckner CD, Storb R, et al. Aplastic anaemia treated by marrow transplantation.Lancet. 1972;I:284–289.

    Article  Google Scholar 

  7. Storb R, Thomas ED, Buckner CD, et al. Allogeneic marrow grafting for treatment of aplastic anemia.Blood. 1974;43:157–180.

    PubMed  CAS  Google Scholar 

  8. 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;296:61–66.

    Article  PubMed  CAS  Google Scholar 

  9. van Bekkum DW, Bach F, Bergan JJ, et al. Bone marrow transplantation from histocompatible, allogeneic donors for aplastic anemia. A report from the ACS/NIH bone marrow transplant registry.JAMA. 1976;236:1131–1135.

    Article  Google Scholar 

  10. Storb R, Weiden PL, Deeg HJ, et al. Rejection of marrow from DLA-identical canine littermates given transfusions before grafting: antigens involved are expressed on leukocytes and skin epithelial cells but not on platelets and red blood cells.Blood. 1979;54:477–484.

    PubMed  CAS  Google Scholar 

  11. Storb R, Prentice RL, Thomas ED, et al. Factors associated with graft rejection after HLA-identical marrow transplantation for aplastic anaemia.Br J Haematol. 1983;55:573–585.

    Article  PubMed  CAS  Google Scholar 

  12. Deeg HJ, Aprile J, Storb R, et al. Functional dendritic cells are required for transfusion-induced sensitization in canine marrow graft recipients.Blood. 1988;71:1138–1140.

    PubMed  CAS  Google Scholar 

  13. Anasetti C, Doney KC, Storb R, et al. Marrow transplantation for severe aplastic anemia: long term outcome in fifty “untransfused” patients.Ann Intern Med. 1986;104:461–466.

    Article  PubMed  CAS  Google Scholar 

  14. Storb R, Sanders JE, Pepe M, et al. Graft-versus-host disease prophylaxis with methotrexate/cyclosporine in children with severe aplastic anemia treated with cyclophosphamide and HLA-identical marrow grafts [letter].Blood. 1991;78:1144–1145.

    PubMed  CAS  Google Scholar 

  15. Bean MA, Storb R, Graham T, et al. Prevention of transfusion-induced sensitization to minor histocompatibility antigens on DLA-identical canine marrow grafts by gamma irradiation of marrow donor blood.Transplantation. 1991;52:956–960.

    Article  PubMed  CAS  Google Scholar 

  16. Bean MA, Graham T, Appelbaum FR, et al. Gamma-irradiation of pretransplant blood transfusions from unrelated donors prevents sensitization to minor histocompatibility antigens on dog leukocyte antigen-identical canine marrow grafts.Transplantation. 1994;57:423–426.

    Article  PubMed  CAS  Google Scholar 

  17. Bortin MM, Gale RP, Rimm AA, for the Advisory Committee of the International Bone Marrow Transplant Registry. Allogeneic bone marrow transplantation for 144 patients with severe aplastic anemia.JAMA. 1981;245:1132–1139.

    Article  PubMed  CAS  Google Scholar 

  18. Gluckman E, Barrett AJ, Arcese W, Devergie A, Degoulet P. Bone marrow transplantation in severe aplastic anemia: a survey of the European Group for Bone Marrow Transplantation (E.G.B.M.T.).Br J Haematol. 1981;49:165–173.

    Article  PubMed  CAS  Google Scholar 

  19. Storb R, Thomas ED, Appelbaum FR, et al. Marrow transplantation for severe aplastic anemia: the Seattle experience. In: Young NS, Levine AS, Humphries RK, eds.Aplastic Anemia: Stem Cell Biology and Advances in Treatment. New York, NY: Alan R. Liss Inc; 1984:297–313.

    Google Scholar 

  20. Deeg HJ, Prentice R, Fritz TE, et al. Increased incidence of malignant tumors in dogs after total body irradiation and marrow transplantation.Int J Radiat Oncol Biol Physiol. 1983;9:1505–1511.

    Article  CAS  Google Scholar 

  21. Deeg HJ, Socié G, Schoch G, et al. Malignancies after marrow transplantation for aplastic anemia and Fanconi anemia: a joint Seattle and Paris analysis of results in 700 patients.Blood. 1996;87:386–392.

    PubMed  CAS  Google Scholar 

  22. Sanders JE, Hawley J, Levy W, et al. Pregnancies following high-dose cyclophosphamide with or without high-dose busulfan or total-body irradiation and bone marrow transplantation.Blood. 1996;87:3045–3052.

    PubMed  CAS  Google Scholar 

  23. Storb R, Doney KC, Thomas ED, et al. Marrow transplantation with or without donor buffy coat cells for 65 transfused aplastic anemia patients.Blood. 1982;59:236–246.

    PubMed  CAS  Google Scholar 

  24. Storb R, Deeg HJ, Farewell V, et al. Marrow transplantation for severe aplastic anemia: methotrexate alone compared with a combination of methotrexate and cyclosporine for prevention of acute graft-versus-host disease.Blood. 1986;68:119–125.

    PubMed  CAS  Google Scholar 

  25. Storb R, Floersheim GL, Weiden PL, et al. Effect of prior blood transfusions on marrow grafts: abrogation of sensitization by procarbazine and antithymocyte serum.J Immunol. 1974;112:1508–1516.

    PubMed  CAS  Google Scholar 

  26. Weiden PL, Storb R, Slichter S, Warren RP, Sale GE. Effect of six weekly transfusions on canine marrow grafts: tests for sensitization and abrogation of sensitization by procarbazine and antithymocyte serum.J Immunol. 1976;117:143–150.

    PubMed  CAS  Google Scholar 

  27. Storb R, Weiden PL, Sullivan KM, et al. Second marrow transplants in patients with aplastic anemia rejecting the first graft: use of a conditioning regimen including cyclophosphamide and antithymocyte globulin.Blood. 1987;70:116–121.

    PubMed  CAS  Google Scholar 

  28. 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.

    PubMed  CAS  Google Scholar 

  29. Storb R, Blume KG, O’Donnell MR, et al. Cyclophosphamide and antithymocyte globulin to condition patients with aplastic anemia for allogeneic marrow transplantations: the experience in four centers.Biol Blood Marrow Transplant 2001;7:39–44.

    Article  PubMed  CAS  Google Scholar 

  30. Locatelli F, Bruno B, Zecca M, et al. Cyclosporin A and short-term methotrexate versus cyclosporin A as graft versus host disease prophylaxis in patients with severe aplastic anemia given allogeneic bone marrow transplantation from an HLA-identical sibling: results of a GITMO/EBMT randomized trial.Blood. 2000;96:1690–1697.

    PubMed  CAS  Google Scholar 

  31. Niederwieser D, Pepe M, Storb R, Loughran TP Jr, Longton G, for the Seattle Marrow Transplant Team. Improvement in rejection, engraftment rate and survival without increase in graft-versus-host disease by high marrow cell dose in patients transplanted for aplas-tic anemia.Br J Haematol. 1988;69:23–28.

    Article  PubMed  CAS  Google Scholar 

  32. Bensinger WI, Martin PJ, Storer B, et al. Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers.N Engl J Med. 2001;344:175–181.

    Article  PubMed  CAS  Google Scholar 

  33. Storb R, Deeg HJ, Whitehead J, et al. Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia.N Engl J Med. 1986;314:729–735.

    Article  PubMed  CAS  Google Scholar 

  34. Nash RA, Pepe MS, Storb R, et al. Acute graft-versus-host disease: analysis of risk factors after allogeneic marrow transplantation and prophylaxis with cyclosporine and methotrexate.Blood. 1992;80:1838–1845.

    PubMed  CAS  Google Scholar 

  35. Storb R, Pepe M, Anasetti C, et al. What role for prednisone in prevention of acute graft-versus-host disease in patients undergoing marrow transplants?Blood. 1990;76:1037–1045.

    PubMed  CAS  Google Scholar 

  36. Chao NJ, Snyder DS, Jain M, et al. Equivalence of 2 effective graftversus-host disease prophylaxis regimens: results of a prospective double-blind randomized trial.Biol Blood Marrow Transplant. 2000;6:254–261.

    Article  PubMed  CAS  Google Scholar 

  37. 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.

    PubMed  CAS  Google Scholar 

  38. Passweg JR, Socié G, Hinterberger W, et al. Bone marrow transplant for severe aplastic anemia: has outcome improved?Blood. 1997;90:858–864.

    PubMed  CAS  Google Scholar 

  39. 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;48:485–490.

    PubMed  CAS  Google Scholar 

  40. Storb R, Prentice RL, Sullivan KM, et al. Predictive factors in chronic graft-versus-host disease in patients with aplastic anemia treated by marrow transplantation from HLA-identical siblings.Ann Intern Med. 1983;98:461–466.

    Article  PubMed  CAS  Google Scholar 

  41. Sullivan KM, Agura E, Anasetti C, et al. Chronic graft-versus-host disease and other late complications of bone marrow transplantation.Semin Hematol. 1991;28:250–259.

    CAS  PubMed  Google Scholar 

  42. Weiden PL, Sullivan KM, Flournoy N, Storb R, Thomas ED, and the Seattle Marrow Transplant Team. Antileukemic effect of chronic graft-versus-host disease. Contribution to improved survival after allogeneic marrow transplantation.N Engl J Med. 1981;304:1529–1533.

    Article  PubMed  CAS  Google Scholar 

  43. Deeg HJ, Leisenring W, Storb R, et al. Long-term outcome after marrow transplantation for severe aplastic anemia.Blood. 1998;91:3637–3645.

    PubMed  CAS  Google Scholar 

  44. Bunin N, Leahey A, Kamani N, August C. Bone marrow transplantation in pediatric patients with severe aplastic anemia: cyclophos-phamide and anti-thymocyte globulin conditioning followed by recombinant human granulocyte-macrophage colony stimulating factor.J Pediatr Hematol Oncol. 1996;18:68–71.

    Article  PubMed  CAS  Google Scholar 

  45. Horstmann M, Stockschlaeder 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  PubMed  CAS  Google Scholar 

  46. Azuma E, Kojima S, Kato K, et al. Conditioning with cyclophos-phamide/antithymocyte globulin for allogeneic bone marrow transplantation from HLA-matched siblings in children with severe aplastic anemia.Bone Marrow Transplant. 1997;19:1085–1087.

    Article  PubMed  CAS  Google Scholar 

  47. 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  PubMed  CAS  Google Scholar 

  48. Hows JM, Yin JL, Marsh J, et al. Histocompatible unrelated volunteer donors compared with HLA nonidentical family donors in marrow transplantation for aplastic anemia and leukemia.Blood. 1986;68:1322–1328.

    PubMed  CAS  Google Scholar 

  49. Gajewski JL, Chattopadhyay A. Treatment of aplastic anemia with bone marrow transplants from closely matched unrelated donors. In: Champlin RE, Gale RP, eds.New Strategies in Bone Marrow Transplantation. New York, NY: Wiley-Liss; 1991:101–108.

    Google Scholar 

  50. Gordon-Smith EC, Fairhead SM, Chipping PM, et al. Bone-marrow transplantation for severe aplastic anaemia using histocompatible unrelated volunteer donors.Br Med J. 1982;285:835–837.

    Article  CAS  Google Scholar 

  51. 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 [letter].Blood. 1994;83:3417–3418.

    PubMed  CAS  Google Scholar 

  52. Gluckman E, Horowitz MM, Champlin RE, et al. Bone marrow transplantation for severe aplastic anemia: influence of conditioning and graft-versus-host disease prophylaxis regimens on outcome.Blood. 1992;79:269–275.

    PubMed  CAS  Google Scholar 

  53. Deeg HJ, Amylon MD, 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  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  55. Vassiliou GS, Webb DKH, Pamphilon D, Knapper S, Veys PA. Improved outcome of alternative marrow donor bone marrow transplantation in children with severe aplastic anemia using a conditioning regimen containing low-dose total body irradiation, cyclophosphamide and Campath.Br J Haematol. 2001;114:701–705.

    Article  PubMed  CAS  Google Scholar 

  56. Petersdorf EW, Gooley TA, Anasetti C, et al. Optimizing outcome after unrelated marrow transplantation by comprehensive matching of HLA class I and II alleles in the donor and recipient.Blood. 1998;92:3515–3520.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

    George E. Georges & Rainer Storb

  2. Department of Medicine, University of Washington, Seattle, Washington, USA

    George E. Georges & Rainer Storb

Authors
  1. George E. Georges
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rainer Storb
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to George E. Georges.

About this article

Cite this article

Georges, G.E., Storb, R. Stem Cell Transplantation for Aplastic Anemia. Int J Hematol 75, 141–146 (2002). https://doi.org/10.1007/BF02982018

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02982018

Key words

Search

Navigation