Radiation Oncology Journal

The Korean Society for Radiation Oncology (대한방사선종양학회)
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Total lymphoid irradiation based conditioning for hematopoietic stem cell transplantation in severe aplastic anemia

  • Lee, Yun-Hee (Department of Radiation Oncology, The Catholic University of Korea College of Medicine) ;
  • Kim, Ji-Yoon (Department of Radiation Oncology, The Catholic University of Korea College of Medicine) ;
  • Choi, Byung-Ock (Department of Radiation Oncology, The Catholic University of Korea College of Medicine) ;
  • Ryu, Mi-Ryeong (Department of Radiation Oncology, The Catholic University of Korea College of Medicine) ;
  • Chung, Su-Mi (Department of Radiation Oncology, The Catholic University of Korea College of Medicine)
  • Received : 2012.09.04
  • Accepted : 2012.10.18
  • Published : 2012.12.30
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Abstract

Purpose: To retrospectively evaluate the outcome and toxicity of total lymphoid irradiation (TLI) based conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in severe aplastic anemia (SAA) patients who experienced an engraftment failure from prior HSCT or were heavily transfused. Materials and Methods: Between 1995 and 2006, 20 SAA patients received TLI for conditioning of HSCT. All patients were multi-transfused or had long duration of disease. Fifteen (75%) patients had graft failure from prior HSCT. In 18 (90%) patients, the donors were human leukocyte antigen identical siblings. The stem cell source was the peripheral blood stem cell in 15 (75%) patients. The conditioning regimen was composed of antithymocyte globulin plus TLI with a median dose of 750 cGy in 1 fraction. The graft-versus-host disease (GVHD) prophylaxis used cyclosporine with methotrexate. Results: With a median follow-up of 10.8 years, graft failures developed in 6 patients. Among them, 3 patients received their third HSCT to be engrafted finally. The Kaplan-Meier overall survival rate was 85.0% and 83.1% at 5 and 10 years, respectively. The incidence of acute and chronic GVHD was 20% and 20%, respectively. None of the patients have developed a malignancy after HSCT. Conclusion: In our study, TLI based conditioning in allogeneic HSCT was feasible with acceptable rates of GVHD in SAA patients who experienced graft failure from prior HSCT or was at a high risk of graft rejection. We achieved relatively better results of engraftment and survival with a long term follow-up.

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References

  1. Horowitz MM. Current status of allogeneic bone marrow transplantation in acquired aplastic anemia. Semin Hematol 2000;37:30-42. https://doi.org/10.1016/S0037-1963(00)90028-3
  2. Young NS, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood 2006;108:2509-19. https://doi.org/10.1182/blood-2006-03-010777
  3. Bacigalupo A. Treatment strategies for patients with severe aplastic anemia. Bone Marrow Transplant 2008;42 Suppl1:S42-4. https://doi.org/10.1038/bmt.2008.113
  4. Ramsay NK, Kim T, Nesbit ME, et al. Total lymphoid irradiation and cyclophosphamide as preparation for bone marrow transplantation in severe aplastic anemia. Blood 1980;55:344-6.
  5. Gluckman E, Socie G, Devergie A, Bourdeau-Esperou H, Traineau R, Cosset JM. Bone marrow transplantation in 107 patients with severe aplastic anemia using cyclophosphamide and thoraco-abdominal irradiation for conditioning: longterm follow-up. Blood 1991;78:2451-5.
  6. Arranz R, Otero MJ, Ramos R, et al. Clinical results in 50 multiply transfused patients with severe aplastic anemia treated with bone marrow transplantation or immunosuppressive therapy. Bone Marrow Transplant 1994;13:383-7.
  7. 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;73:606-13.
  8. Choi DR, Choi IB, Kang KM, Shinn KS, Kim CC. Total body irradiation technique: basic data measurements and in vivo dosimetry. J Korean Soc Ther Radiol 1994;12:219-24.
  9. Slavin S, Strober S, Fuks Z, Kaplan HS. Induction of specific tissue transplantation tolerance using fractionated total lymphoid irradiation in adult mice: long-term survival of allogeneic bone marrow and skin grafts. J Exp Med 1977;146:34-48. https://doi.org/10.1084/jem.146.1.34
  10. Kersey JH, Kruger J, Song C, Kloster B. Prolonged bone marrow and skin allograft survival after pretransplant conditioning with cyclophosphamide and total lymphoid irradiation. Transplantation 1980;29:388-91. https://doi.org/10.1097/00007890-198005000-00008
  11. Sanders JE. The impact of marrow transplant preparative regimens on subsequent growth and development: The Seattle Marrow Transplant Team. Semin Hematol 1991;28:244-9.
  12. Ades L, Mary JY, Robin M, et al. Long-term outcome after bone marrow transplantation for severe aplastic anemia. Blood 2004;103:2490-7. https://doi.org/10.1182/blood-2003-07-2546
  13. Socie G, Henry-Amar M, Cosset JM, Devergie A, Girinsky T, Gluckman E. Increased incidence of solid malignant tumors after bone marrow transplantation for severe aplastic anemia. Blood 1991;78:277-9.
  14. Camitta BM, Thomas ED, Nathan DG, et al. Severe aplastic anemia: a prospective study of the effect of early marrow transplantation on acute mortality. Blood 1976;48:63-70.
  15. Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant 1995;15:825-8.
  16. Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. diagnosis and staging working group report. Biol Blood Marrow Transplant 2005;11:945-56. https://doi.org/10.1016/j.bbmt.2005.09.004
  17. Fuks Z, Strober S, Bobrove AM, Sasazuki T, McMichael A, Kaplan HS. Long term effects of radiation of T and B lymphocytes in peripheral blood of patients with Hodgkin's disease. J Clin Invest 1976;58:803-14. https://doi.org/10.1172/JCI108532
  18. Lowsky R, Takahashi T, Liu YP, et al. Protective conditioning for acute graft-versus-host disease. N Engl J Med 2005;353:1321-31. https://doi.org/10.1056/NEJMoa050642
  19. Gaziev D, Giardini C, Galimberti M, et al. Bone marrow transplantation for transfused patients with severe aplastic anemia using cyclophosphamide and total lymphoid irradiation as conditioning therapy: long-term follow-up from a single center. Bone Marrow Transplant 1999;24:253-7. https://doi.org/10.1038/sj.bmt.1701887
  20. Novitzky N, Thomas V, Stubbings H, Hale G, Waldmann H. Radiotherapy-based conditioning is effective immunosuppression for patients undergoing transplantation with T-cell depleted stem cell grafts for severe aplasia. Cytotherapy 2004;6:450-6. https://doi.org/10.1080/14653240410004970
  21. Inamoto Y, Suzuki R, Kuwatsuka Y, et al. Long-term outcome after bone marrow transplantation for aplastic anemia using cyclophosphamide and total lymphoid irradiation as conditioning regimen. Biol Blood Marrow Transplant 2008;14:43-9.
  22. Storek J, Gooley T, Siadak M, et al. Allogeneic peripheral blood stem cell transplantation may be associated with a high risk of chronic graft-versus-host disease. Blood 1997;90:4705-9.
  23. Deeg HJ, Socie 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;87:386-92.
  24. Bhatia S, Ramsay NK, Steinbuch M, et al. Malignant neoplasms following bone marrow transplantation. Blood 1996;87:3633-9.
  25. 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;13:233-7.
  26. Heinzelmann F, Lang PJ, Ottinger H, et al. Immunosuppressive total lymphoid irradiation-based reconditioning regimens enable engraftment after graft rejection or graft failure in patients treated with allogeneic hematopoietic stem cell transplantation. Int J Radiat Oncol Biol Phys 2008;70:523-8. https://doi.org/10.1016/j.ijrobp.2007.06.037

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