Summary:
Busulfan was added at the dose of 4 mg/kg to 200 mg/kg cyclophosphamide in 81 patients (3–53 years, median 24) with aplastic anemia to reduce graft rejection. Graft-versus-host disease (GVHD) prophylaxis comprised cyclosporine–methotrexate. The number of prior transfusions was 0–276 (median 26), and 48% had received prior immunosuppressive therapy. Two patients experienced primary graft failure, and 10 secondary rejection at 28–1001 days (median 317 days). The cumulative incidence of rejection was 22%; for heavily transfused patients (⩾50 U) it was 43% compared to 16% for the rest (P=0.06). Overall survival rate at 8 years was 56%; patients who received ⩽15 and >15 transfusions was 78 and 50%, respectively (P=0.01), whereas it was 67 and 28% for ⩽50 and >50 transfusions, respectively (P=0.002). In multivariate analysis, higher number of prior transfusions, shorter period of immunosuppression with cyclosporine and GVHD were associated with inferior survival; moreover, a higher risk of graft rejection were associated with a higher number of prior transfusions and a trend was observed for a shorter cyclosporine administration. Low-dose busulfan is feasible and may be helpful in patients exposed to <50 transfusions. However, rejection remains a significant problem, mainly in heavily transfused patients.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
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.
Bacigalupo A, Brand R, Oneto R et al. Treatment of acquired severe aplastic anemia: bone marrow transplantation compared with immunosuppressive therapy – The European Group for Blood and Marrow Transplantation experience. Semin Hematol 2000; 37: 69–80.
Horowitz MM . Current status of allogeneic bone marrow transplantation in acquired aplastic anemia. Semin Hematol 2000; 37: 30–42.
Stucki A, Leisenring W, Sandmaier BM et al. Decreased rejection and improved survival of first and second marrow transplants for severe aplastic anemia (a 26-year retrospective analysis). Blood 1998; 92: 2742–2749.
Deeg HJ, Leisenring W, Storb R et al. Long-term outcome after marrow transplantation for severe aplastic anemia. Blood 1998; 91: 3637–3645.
Anonymous. Bone marrow transplantation from donors with aplastic anemia. A report from the ACS/NIH bone marrow transplant registry. JAMA 1976; 236: 1131–1135.
UCLA Bone Marrow Transplant Team. Bone-marrow transplantation in severe aplastic anaemia. Lancet 1976; 2: 921–923.
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.
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.
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: 344–346.
Feig SA, Champlin R, Arenson E et al. Improved survival following bone marrow transplantation for aplastic anaemia. Br J Haematol 1983; 54: 509–517.
Bacigalupo A, Hows J, Gluckman E et al. Bone marrow transplantation (BMT) versus immunosuppression for the treatment of severe aplastic anaemia (SAA): a report of the EBMT SAA working party. Br J Haematol 1988; 70: 177–182.
Locasciulli A, van't Veer L, Bacigalupo A et al. Treatment with marrow transplantation or immunosuppression of childhood acquired severe aplastic anemia: a report from the EBMT SAA Working Party. Bone Marrow Transplant 1990; 6: 211–217.
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.
Addison IE . Immunosuppression with busulphan: the effect on spleen, marrow and thymus cells of mice. Eur J Immunol 1973; 3: 419–424.
Tutschka PJ, Santon GW . Bone marrow transplantation in the busulphan-treated rat. III. Relationship between myelosuppression and immunosuppression for conditioning bone marrow recipients. Transplantation 1977; 24: 52–62.
Floersheim GL, Elsons LA . Restoration of hematopoiesis following a lethal dose of dimethyl myleran by isologic bone marrow transplantation in mice. Experiments on modification of intolerance to homologous bone marrow by 6-mercaptopurine, amino-chlorambucil and cortisone. Acta Haematol 1961; 26: 233–245.
Tutschka PJ, Copelan EA, Klein JP . Bone marrow transplantation for leukemia following a new busulfan and cyclophosphamide regimen. Blood 1987; 70: 1382–1388.
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.
Storb R, Raff RF, Appelbaum FR et al. The influence of transfusions from unrelated DLA-matched or mismatched donors upon marrow grafts between DLA-identical canine littermates. Transplantation 1988; 46: 334–336.
Storb R, Epstein RB, Rudolph RH et al. The effect of prior transfusion on marrow grafts between histocompatible canine siblings. J Immunol 1970; 105: 627–633.
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.
Acknowledgements
We acknowledge Arlete Rocha for her Secretariat assistance.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Dulley, F., Vigorito, A., Aranha, F. et al. Addition of low-dose busulfan to cyclophosphamide in aplastic anemia patients prior to allogeneic bone marrow transplantation to reduce rejection. Bone Marrow Transplant 33, 9–13 (2004). https://doi.org/10.1038/sj.bmt.1704325
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bmt.1704325
Keywords
This article is cited by
-
Bulsufan decreases the incidence of mixed chimaerism in HLA-matched donor transplantation for severe aplastic anaemia
Bone Marrow Transplantation (2022)
-
Optimizing conditioning regimen with low-dose irradiation or busulfan enables the outcome of transplantation from a 6–7/8 HLA-matched donor comparable to that from an 8/8 HLA-matched unrelated donor in severe aplastic anemia patients under 40 years
Annals of Hematology (2021)
-
The impact of low dose busulfan on gonodal function after allogeneic hematopoietic stem cell transplantation for aplastic anemia
Bone Marrow Transplantation (2020)
-
Upfront haploidentical transplant for acquired severe aplastic anemia: registry-based comparison with matched related transplant
Journal of Hematology & Oncology (2017)
-
The Latin American experience of allografting patients with severe aplastic anaemia: real-world data on the impact of stem cell source and ATG administration in HLA-identical sibling transplants
Bone Marrow Transplantation (2017)