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

Non-total body irradiation containing preparative regimen in alternative donor bone marrow transplantation for severe aplastic anemia

Summary:

Using non-total body irradiation (TBI) containing preparative regimens, 13 patients with severe aplastic anemia (SAA) were transplanted from an alternative donor in a single institute. In total, 12 donors were unrelated volunteers and one was an HLA one-locus mismatched sibling. Median time from diagnosis of SAA to bone marrow transplantation (BMT) was 10.1 months (range, 1.6–180.1). Nine patients had received immunosuppressive treatment with ATG before BMT, while four had not. Preparative regimens consisted of cyclophosphamide plus ATG in nine patients, cyclophosphamide plus fludarabine in two patients, and cyclophosphamide plus fludarabine plus ATG in two patients. All patients received non-T-cell depleted bone marrow from the donor. Cyclosporine plus methotrexate were given for GVHD prophylaxis. All patients engrafted on a median of day 21 (range, 15–27). Grade III–IV acute GVHD developed in three (23%) of 13 patients and extensive chronic GVHD in four (31%) of 12 evaluable patients. With a median follow-up duration of 1138 days (range, 118–1553), 10 patients are alive with durable engraftment showing 74.6% (95% confidence interval, 49.5–99.7%) of survival rate. Cause of the deaths was CNS bleeding in one and chronic GVHD in two. In conclusion, non-TBI containing preparative regimen could ensure durable engraftment in alternative donor BMT for SAA and showed promising results.

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

Figure 1

Similar content being viewed by others

References

  1. Marsh JC, Gordon-Smith EC . Treatment options in severe aplastic anaemia. Lancet 1998; 351: 1830–1831.

    Article  CAS  PubMed  Google Scholar 

  2. Young NS, Barrett AJ . The treatment of severe acquired aplastic anemia. Blood 1995; 85: 3367–3377.

    CAS  PubMed  Google Scholar 

  3. Frickhofen N, Kaltwasser JP, Schrezenmeier H et al. Treatment of aplastic anemia with antilymphocyte globulin and methylprednisolone with or without cyclosporine. The German Aplastic Anemia Study Group. N Engl J Med 1991; 324: 1297–1304.

    Article  CAS  PubMed  Google Scholar 

  4. Bacigalupo A, Broccia G, Corda G et al. Antilymphocyte globulin, cyclosporin, and granulocyte colony-stimulating factor in patients with acquired severe aplastic anemia (SAA): a pilot study of the EBMT SAA Working Party. Blood 1995; 85: 1348–1353.

    CAS  PubMed  Google Scholar 

  5. Margolis DA, Casper JT . Alternative-donor hematopoietic stem-cell transplantation for severe aplastic anemia. Semin Hematol 2000; 37: 43–55.

    Article  CAS  PubMed  Google Scholar 

  6. Margolis D, Camitta B, Pietryga D et al. Unrelated donor bone marrow transplantation to treat severe aplastic anaemia in children and young adults. Br J Haematol 1996; 94: 65–72.

    Article  CAS  PubMed  Google Scholar 

  7. Kojima S, Inaba J, Kondo M et al. Unrelated donor marrow transplantation for severe acquired aplastic anemia using cyclophosphamide, antithymocyte globulin, and total body irradiation. Blood 1995; 85: 291–292.

    CAS  PubMed  Google Scholar 

  8. Wagner JL, Deeg HJ, Seidel K et al. Bone marrow transplantation for severe aplastic anemia from genotypically HLA-nonidentical relatives. An update of the Seattle experience. Transplantation 1996; 61: 54–61.

    Article  CAS  PubMed  Google Scholar 

  9. 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.

    CAS  PubMed  Google Scholar 

  10. 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.

    CAS  PubMed  Google Scholar 

  11. Curtis RE, Rowlings PA, Deeg HJ et al. Solid cancers after bone marrow transplantation. N Engl J Med 1997; 336: 897–904.

    Article  CAS  PubMed  Google Scholar 

  12. Storb R, Deeg HJ . Failure of allogeneic canine marrow grafts after total-body irradiation. Allogeneic ‘resistance’ versus transfusion-induced sensitization. Transplantation 1986; 42: 571–580.

    Article  CAS  PubMed  Google Scholar 

  13. Storb R, Thomas ED, Buckner CD et al. Marrow transplantation in thirty ‘untransfused’ patients with severe aplastic anemia. Ann Intern Med 1980; 92: 30–36.

    Article  CAS  PubMed  Google Scholar 

  14. 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  CAS  PubMed  Google Scholar 

  15. 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  PubMed  Google Scholar 

  16. 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  PubMed  Google Scholar 

  17. 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  CAS  PubMed  Google Scholar 

  18. 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  CAS  PubMed  Google Scholar 

  19. Bean MA, Graham T, Appelbaum FR et al. Gamma radiation of blood products prevents rejection of subsequent DLA-identical marrow grafts. Tolerance versus abrogation of sensitization to non-DLA antigens. Transplantation 1996; 61: 334–335.

    Article  CAS  PubMed  Google Scholar 

  20. Storb R, Bean MA, Appelbaum FR et al. Treatment of marrow donor blood products with gamma-irradiation prevents transfusion-induced sensitization to DLA-identical marrow grafts. Transplant Proc 1991; 23: 1697–1698.

    CAS  PubMed  Google Scholar 

  21. 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, Inc.: Malden, 2004, pp 981–1001.

    Google Scholar 

  22. 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  PubMed  Google Scholar 

  23. 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 

  24. 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  PubMed  Google Scholar 

  25. Horowitz MM . Current status of allogeneic bone marrow transplantation in acquired aplastic anemia. Semin Hematol 2000; 37: 30–42.

    Article  CAS  PubMed  Google Scholar 

  26. 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 

  27. 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 

  28. Elebute MO, Ball SE, Gordon-Smith EC et al. Autologous recovery following non-myeloablative unrelated donor bone marrow transplantation for severe aplastic anaemia. Ann Hematol 2002; 81: 378–381.

    Article  CAS  PubMed  Google Scholar 

  29. 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 

  30. Lee JH, Lee JH, Lee JS et al. Cyclophosphamide and antithymocyte globulin conditioning may be sufficient for Korean patients with early stage severe aplastic anemia transplanted with marrow from donors other than HLA-identical siblings. Haematologica 2001; 86: 434–435.

    CAS  PubMed  Google Scholar 

  31. Camitta BM, Rappeport JM, Parkman R, Nathan DG . Selection of patients for bone marrow transplantation in severe aplastic anemia. Blood 1975; 45: 355–363.

    CAS  PubMed  Google Scholar 

  32. Hopkins KA . Basic microlymphocytotoxicity test. In: Zachary AA, Teresi GA (ed.). Laboratory Manual. American Society of Histocompatibility and Immunogenetics: Lenexa, 1990, pp 195–201.

    Google Scholar 

  33. Shulman HM, Sullivan KM, Weiden PL et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med 1980; 69: 204–217.

    Article  CAS  PubMed  Google Scholar 

  34. Tutschka PJ, Beschorner WE, Hess AD, Santos GW . Cyclosporin-A to prevent graft-versus-host disease: a pilot study in 22 patients receiving allogeneic marrow transplants. Blood 1983; 61: 318–325.

    CAS  PubMed  Google Scholar 

  35. Przepiorka D, Anderlini P, Saliba R et al. Chronic graft-versus-host disease after allogeneic blood stem cell transplantation. Blood 2001; 98: 1695–1700.

    Article  CAS  PubMed  Google Scholar 

  36. Przepiorka D, Khouri I, Ippoliti C et al. Tacrolimus and minidose methotrexate for prevention of acute graft-versus-host disease after HLA-mismatched marrow or blood stem cell transplantation. Bone Marrow Transplant 1999; 24: 763–768.

    Article  CAS  PubMed  Google Scholar 

  37. McDonald GB, Hinds MS, Fisher LD et al. Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients. Ann Intern Med 1993; 118: 255–267.

    Article  CAS  PubMed  Google Scholar 

  38. Bearman SI . The syndrome of hepatic veno-occlusive disease after marrow transplantation. Blood 1995; 85: 3005–3020.

    CAS  PubMed  Google Scholar 

  39. Gleaves CA, Smith TF, Shuster EA, Pearson GR . Comparison of standard tube and shell vial cell culture techniques for the detection of cytomegalovirus in clinical specimens. J Clin Microbiol 1985; 21: 217–221.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Pancholi P, Wu F, Della-Latta P . Rapid detection of cytomegalovirus infection in transplant patients. Expert Rev Mol Diagn 2004; 4: 231–242.

    Article  CAS  PubMed  Google Scholar 

  41. St George K, Rinaldo Jr CR . Comparison of cytomegalovirus antigenemia and culture assays in patients on and off antiviral therapy. J Med Virol 1999; 59: 91–97.

    Article  CAS  PubMed  Google Scholar 

  42. Choi SJ, Lee KH, Lee JH et al. Prognostic value of hematopoietic chimerism in patients with acute leukemia after allogeneic bone marrow transplantation: a prospective study. Bone Marrow Transplant 2000; 26: 327–332.

    Article  CAS  PubMed  Google Scholar 

  43. 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 

  44. Hows J, Szydlo R, Anasetti C et al. Unrelated donor marrow transplants for severe acquired aplastic anemia. Bone Marrow Transplant 1992; 10 (Suppl 1): 102–106.

    PubMed  Google Scholar 

  45. 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 

  46. Morishima Y, Kodera Y, Hirabayashi N et al. Low incidence of acute GVHD in patients transplanted with marrow from HLA-A,B,DR-compatible unrelated donors among Japanese. Bone Marrow Transplant 1995; 15: 235–239.

    CAS  PubMed  Google Scholar 

  47. Lin MT, Storer B, Martin PJ et al. Relation of an interleukin-10 promoter polymorphism to graft-versus-host disease and survival after hematopoietic-cell transplantation. N Engl J Med 2003; 349: 2201–2210.

    Article  CAS  PubMed  Google Scholar 

  48. Deeg HJ, Spitzer TR, Cottler-Fox M et al. Conditioning-related toxicity and acute graft-versus-host disease in patients given methotrexate/cyclosporine prophylaxis. Bone Marrow Transplant 1991; 7: 193–198.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J-H Lee.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, JH., Choi, SJ., Lee, JH. et al. Non-total body irradiation containing preparative regimen in alternative donor bone marrow transplantation for severe aplastic anemia. Bone Marrow Transplant 35, 755–761 (2005). https://doi.org/10.1038/sj.bmt.1704880

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704880

Keywords

This article is cited by

Search

Quick links