Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Treatment of aplastic anemia in adults

Stanley L Schrier, MD
Section Editor
William C Mentzer, MD
Deputy Editor
Alan G Rosmarin, MD


Aplastic anemia (AA) is a disorder of hematopoietic stem cells that causes pancytopenia and a hypocellular bone marrow without splenomegaly. Affected patients typically present with recurrent infections due to neutropenia, bleeding episodes due to thrombocytopenia, and fatigue due to anemia. Patients with AA are at risk of life-threatening complications, especially when pancytopenia is severe. Thus, a long-term approach to therapy is needed.

This topic reviews the treatment and prognosis of AA in adults. Additional topics discuss the diagnosis of AA, the management of inherited and acquired AA in children and adolescents, and the role of hematopoietic cell transplantation (HCT) for AA:


Diagnosis – (See "Aplastic anemia: Pathogenesis; clinical manifestations; and diagnosis".)

Role of HCT – (See "Hematopoietic cell transplantation for aplastic anemia in adults".)


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Sep 8, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Brodsky RA, Jones RJ. Aplastic anaemia. Lancet 2005; 365:1647.
  2. Young NS, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood 2006; 108:2509.
  3. Scheinberg P, Young NS. How I treat acquired aplastic anemia. Blood 2012; 120:1185.
  4. Marsh JC, Ball SE, Cavenagh J, et al. Guidelines for the diagnosis and management of aplastic anaemia. Br J Haematol 2009; 147:43.
  5. Tichelli A, Marsh JC. Treatment of aplastic anaemia in elderly patients aged >60 years. Bone Marrow Transplant 2013; 48:180.
  6. 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.
  7. Guinan EC. Diagnosis and management of aplastic anemia. Hematology Am Soc Hematol Educ Program 2011; 2011:76.
  8. Höchsmann B, Moicean A, Risitano A, et al. Supportive care in severe and very severe aplastic anemia. Bone Marrow Transplant 2013; 48:168.
  9. Desmond R, Townsley DM, Dunbar C, Young NS. Eltrombopag in aplastic anemia. Semin Hematol 2015; 52:31.
  10. Schrezenmeier H, Körper S, Höchsmann B. [Aplastic anemia: Current state of diagnosis and treatment]. Internist (Berl) 2015; 56:989.
  11. Risitano AM. Aplastic Anemia: Alternative Immunosuppressive Treatments and Eltrombopag. A report from the 2014 EBMT Educational Meeting from the Severe Aplastic Anaemia and Infectious Diseases Working Parties. Curr Drug Targets 2015.
  12. Peinemann F, Bartel C, Grouven U. First-line allogeneic hematopoietic stem cell transplantation of HLA-matched sibling donors compared with first-line ciclosporin and/or antithymocyte or antilymphocyte globulin for acquired severe aplastic anemia. Cochrane Database Syst Rev 2013; :CD006407.
  13. 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.
  14. Passweg JR, Socié G, Hinterberger W, et al. Bone marrow transplantation for severe aplastic anemia: has outcome improved? Blood 1997; 90:858.
  15. Paquette RL, Tebyani N, Frane M, et al. Long-term outcome of aplastic anemia in adults treated with antithymocyte globulin: comparison with bone marrow transplantation. Blood 1995; 85:283.
  16. Tichelli A, Socié G, Henry-Amar M, et al. Effectiveness of immunosuppressive therapy in older patients with aplastic anemia. European Group for Blood and Marrow Transplantation Severe Aplastic Anaemia Working Party. Ann Intern Med 1999; 130:193.
  17. Kao SY, Xu W, Brandwein JM, et al. Outcomes of older patients (> or = 60 years) with acquired aplastic anaemia treated with immunosuppressive therapy. Br J Haematol 2008; 143:738.
  18. Gonzalez-Casas R, Garcia-Buey L, Jones EA, et al. Systematic review: hepatitis-associated aplastic anaemia--a syndrome associated with abnormal immunological function. Aliment Pharmacol Ther 2009; 30:436.
  19. Itterbeek P, Vandenberghe P, Nevens F, et al. Aplastic anemia after transplantation for non-A, non-B, non-C fulminant hepatic failure: case report and review of the literature. Transpl Int 2002; 15:117.
  20. Dunn DE, Tanawattanacharoen P, Boccuni P, et al. Paroxysmal nocturnal hemoglobinuria cells in patients with bone marrow failure syndromes. Ann Intern Med 1999; 131:401.
  21. Piaggio G, Podestà M, Pitto A, et al. Coexistence of normal and clonal haemopoiesis in aplastic anaemia patients treated with immunosuppressive therapy. Br J Haematol 1999; 107:505.
  22. 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.
  23. Frickhofen N, Heimpel H, Kaltwasser JP, et al. Antithymocyte globulin with or without cyclosporin A: 11-year follow-up of a randomized trial comparing treatments of aplastic anemia. Blood 2003; 101:1236.
  24. Scheinberg P, Nunez O, Weinstein B, et al. Horse versus rabbit antithymocyte globulin in acquired aplastic anemia. N Engl J Med 2011; 365:430.
  25. Yoshimi A, Niemeyer CM, Führer MM, Strahm B. Comparison of the efficacy of rabbit and horse antithymocyte globulin for the treatment of severe aplastic anemia in children. Blood 2013; 121:860.
  26. Atta EH, Dias DS, Marra VL, de Azevedo AM. Comparison between horse and rabbit antithymocyte globulin as first-line treatment for patients with severe aplastic anemia: a single-center retrospective study. Ann Hematol 2010; 89:851.
  27. Shin SH, Yoon JH, Yahng SA, et al. The efficacy of rabbit antithymocyte globulin with cyclosporine in comparison to horse antithymocyte globulin as a first-line treatment in adult patients with severe aplastic anemia: a single-center retrospective study. Ann Hematol 2013; 92:817.
  28. Samarasinghe S, Marsh J, Dufour C. Immune suppression for childhood acquired aplastic anemia and myelodysplastic syndrome: where next? Haematologica 2014; 99:597.
  29. Rosenfeld S, Follmann D, Nunez O, Young NS. Antithymocyte globulin and cyclosporine for severe aplastic anemia: association between hematologic response and long-term outcome. JAMA 2003; 289:1130.
  30. Holt DW, Johnston A, Kahan BD, et al. New approaches to cyclosporine monitoring raise further concerns about analytical techniques. Clin Chem 2000; 46:872.
  31. http://www.fda.gov/downloads/biologicsbloodvaccines/bloodbloodproducts/approvedproducts/licensedproductsblas/fractionatedplasmaproducts/ucm199603.pdf (Accessed on September 10, 2015).
  32. http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM117134.pdf (Accessed on September 10, 2015).
  33. Scheinberg P, Fischer SH, Li L, et al. Distinct EBV and CMV reactivation patterns following antibody-based immunosuppressive regimens in patients with severe aplastic anemia. Blood 2007; 109:3219.
  34. Marsh JC, Socie G, Schrezenmeier H, et al. Haemopoietic growth factors in aplastic anaemia: a cautionary note. European Bone Marrow Transplant Working Party for Severe Aplastic Anaemia. Lancet 1994; 344:172.
  35. Deyell RJ, Shereck EB, Milner RA, Schultz KR. Immunosuppressive therapy without hematopoietic growth factor exposure in pediatric acquired aplastic anemia. Pediatr Hematol Oncol 2011; 28:469.
  36. Kadia TM, Borthakur G, Garcia-Manero G, et al. Final results of the phase II study of rabbit anti-thymocyte globulin, ciclosporin, methylprednisone, and granulocyte colony-stimulating factor in patients with aplastic anaemia and myelodysplastic syndrome. Br J Haematol 2012; 157:312.
  37. Bacigalupo A, Bruno B, Saracco P, et al. Antilymphocyte globulin, cyclosporine, prednisolone, and granulocyte colony-stimulating factor for severe aplastic anemia: an update of the GITMO/EBMT study on 100 patients. European Group for Blood and Marrow Transplantation (EBMT) Working Party on Severe Aplastic Anemia and the Gruppo Italiano Trapianti di Midolio Osseo (GITMO). Blood 2000; 95:1931.
  38. 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.
  39. Socie G, Mary JY, Schrezenmeier H, et al. Granulocyte-stimulating factor and severe aplastic anemia: a survey by the European Group for Blood and Marrow Transplantation (EBMT). Blood 2007; 109:2794.
  40. Locasciulli A, Bruno B, Rambaldi A, et al. Treatment of severe aplastic anemia with antilymphocyte globulin, cyclosporine and two different granulocyte colony-stimulating factor regimens: a GITMO prospective randomized study. Haematologica 2004; 89:1054.
  41. Kojima S, Hibi S, Kosaka Y, et al. Immunosuppressive therapy using antithymocyte globulin, cyclosporine, and danazol with or without human granulocyte colony-stimulating factor in children with acquired aplastic anemia. Blood 2000; 96:2049.
  42. Gluckman E, Rokicka-Milewska R, Hann I, et al. Results and follow-up of a phase III randomized study of recombinant human-granulocyte stimulating factor as support for immunosuppressive therapy in patients with severe aplastic anaemia. Br J Haematol 2002; 119:1075.
  43. Teramura M, Kimura A, Iwase S, et al. Treatment of severe aplastic anemia with antithymocyte globulin and cyclosporin A with or without G-CSF in adults: a multicenter randomized study in Japan. Blood 2007; 110:1756.
  44. Tichelli A, Schrezenmeier H, Socié G, et al. A randomized controlled study in patients with newly diagnosed severe aplastic anemia receiving antithymocyte globulin (ATG), cyclosporine, with or without G-CSF: a study of the SAA Working Party of the European Group for Blood and Marrow Transplantation. Blood 2011; 117:4434.
  45. Scheinberg P, Nunez O, Wu C, Young NS. Treatment of severe aplastic anaemia with combined immunosuppression: anti-thymocyte globulin, ciclosporin and mycophenolate mofetil. Br J Haematol 2006; 133:606.
  46. Brodsky RA, Chen AR, Dorr D, et al. High-dose cyclophosphamide for severe aplastic anemia: long-term follow-up. Blood 2010; 115:2136.
  47. Tisdale JF, Dunn DE, Geller N, et al. High-dose cyclophosphamide in severe aplastic anaemia: a randomised trial. Lancet 2000; 356:1554.
  48. Socié G. Cyclophosphamide in aplastic anemia? Blood 2010; 115:2120.
  49. Scheinberg P, Townsley D, Dumitriu B, et al. Moderate-dose cyclophosphamide for severe aplastic anemia has significant toxicity and does not prevent relapse and clonal evolution. Blood 2014; 124:2820.
  50. Zhang F, Zhang L, Jing L, et al. High-dose cyclophosphamide compared with antithymocyte globulin for treatment of acquired severe aplastic anemia. Exp Hematol 2013; 41:328.
  51. https://www.clinicaltrials.gov/ct2/show/NCT02404025 (Accessed on September 18, 2015).
  52. https://www.clinicaltrials.gov/ct2/show/NCT01328587 (Accessed on September 18, 2015).
  53. https://www.clinicaltrials.gov/ct2/show/NCT01703169 (Accessed on September 18, 2015).
  54. https://www.clinicaltrials.gov/ct2/show/NCT01891994 (Accessed on September 18, 2015).
  55. https://www.clinicaltrials.gov/ct2/show/NCT02099747 (Accessed on September 18, 2015).
  56. https://www.clinicaltrials.gov/ct2/show/NCT01623167 (Accessed on September 18, 2015).
  57. Maciejewski JP, Sloand EM, Nunez O, et al. Recombinant humanized anti-IL-2 receptor antibody (daclizumab) produces responses in patients with moderate aplastic anemia. Blood 2003; 102:3584.
  58. Sloand EM, Olnes MJ, Weinstein B, et al. Long-term follow-up of patients with moderate aplastic anemia and pure red cell aplasia treated with daclizumab. Haematologica 2010; 95:382.
  59. Song Y, Li N, Liu Y, Fang B. Improved outcome of adults with aplastic anaemia treated with arsenic trioxide plus ciclosporin. Br J Haematol 2013; 160:266.
  60. Wei J, Huang Z, Guo J, et al. Porcine antilymphocyte globulin (p-ALG) plus cyclosporine A (CsA) treatment in acquired severe aplastic anemia: a retrospective multicenter analysis. Ann Hematol 2015; 94:955.
  61. Sloand EM, Read EJ, Scheinberg P, et al. Mobilization, collection, and immunomagnetic selection of peripheral blood CD34 cells in recovered aplastic anemia patients. Transfusion 2007; 47:1250.
  62. Schrezenmeier H, Marin P, Raghavachar A, et al. Relapse of aplastic anaemia after immunosuppressive treatment: a report from the European Bone Marrow Transplantation Group SAA Working Party. Br J Haematol 1993; 85:371.
  63. Rosenfeld SJ, Kimball J, Vining D, Young NS. Intensive immunosuppression with antithymocyte globulin and cyclosporine as treatment for severe acquired aplastic anemia. Blood 1995; 85:3058.
  64. Tichelli A, Passweg J, Nissen C, et al. Repeated treatment with horse antilymphocyte globulin for severe aplastic anaemia. Br J Haematol 1998; 100:393.
  65. Füreder W, Valent P. Treatment of refractory or relapsed acquired aplastic anemia: review of established and experimental approaches. Leuk Lymphoma 2011; 52:1435.
  66. Olnes MJ, Scheinberg P, Calvo KR, et al. Eltrombopag and improved hematopoiesis in refractory aplastic anemia. N Engl J Med 2012; 367:11.
  67. Desmond R, Townsley DM, Dumitriu B, et al. Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug. Blood 2014; 123:1818.
  68. Oshima Y, Yuji K, Tojo A. Eltrombopag in refractory aplastic anemia. N Engl J Med 2012; 367:1162; author reply 1163.
  69. Scheinberg P, Nunez O, Weinstein B, et al. Activity of alemtuzumab monotherapy in treatment-naive, relapsed, and refractory severe acquired aplastic anemia. Blood 2012; 119:345.
  70. Risitano AM, Selleri C, Serio B, et al. Alemtuzumab is safe and effective as immunosuppressive treatment for aplastic anaemia and single-lineage marrow failure: a pilot study and a survey from the EBMT WPSAA. Br J Haematol 2010; 148:791.
  71. Kim H, Min YJ, Baek JH, et al. A pilot dose-escalating study of alemtuzumab plus cyclosporine for patients with bone marrow failure syndrome. Leuk Res 2009; 33:222.
  72. Gómez-Almaguer D, Jaime-Pérez JC, Garza-Rodríguez V, et al. Subcutaneous alemtuzumab plus cyclosporine for the treatment of aplastic anemia. Ann Hematol 2010; 89:299.
  73. Risitano AM, Schrezenmeier H. Alternative immunosuppression in patients failing immunosuppression with ATG who are not transplant candidates: Campath (Alemtuzumab). Bone Marrow Transplant 2013; 48:186.
  74. http://www.accessdata.fda.gov/drugsatfda_docs/label/2001/alemmil050701LB.htm (Accessed on September 15, 2015).
  75. Scheinberg P, Townsley D, Dumitriu B, et al. Horse antithymocyte globulin as salvage therapy after rabbit antithymocyte globulin for severe aplastic anemia. Am J Hematol 2014; 89:467.
  76. Di Bona E, Rodeghiero F, Bruno B, et al. Rabbit antithymocyte globulin (r-ATG) plus cyclosporine and granulocyte colony stimulating factor is an effective treatment for aplastic anaemia patients unresponsive to a first course of intensive immunosuppressive therapy. Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Br J Haematol 1999; 107:330.
  77. Brodsky RA, Chen AR, Brodsky I, Jones RJ. High-dose cyclophosphamide as salvage therapy for severe aplastic anemia. Exp Hematol 2004; 32:435.
  78. Scheinberg P. Aplastic anemia: therapeutic updates in immunosuppression and transplantation. Hematology Am Soc Hematol Educ Program 2012; 2012:292.
  79. Young NS. Aplastic anaemia. Lancet 1995; 346:228.
  80. Scheinberg P, Wu CO, Nunez O, Young NS. Predicting response to immunosuppressive therapy and survival in severe aplastic anaemia. Br J Haematol 2009; 144:206.
  81. Bacigalupo A. Aetiology of severe aplastic anaemia and outcome after allogeneic bone marrow transplantation or immunosuppression therapy. Working Party on Severe Aplastic Anaemia of the European Blood and Marrow Transplantation Group. Eur J Haematol Suppl 1996; 60:16.
  82. Tichelli A, Socié G, Marsh J, et al. Outcome of pregnancy and disease course among women with aplastic anemia treated with immunosuppression. Ann Intern Med 2002; 137:164.