title: Management of the refractory aplastic anemia patient: what are the options?
abstract: Refractory aplastic anemia (AA) is defined as a lack of response to first-line immunosuppressive therapy (IST) with antithymocyte globulin and cyclosporin and is manifested as persistence of severe cytopenias at 6 months after IST. Although supportive care is critical for AA patients, it is of paramount importance for refractory disease in view of the longer duration of pancytopenia and susceptibility to life-threatening infections due to IST. Improvements in supportive care have largely contributed to better outcome over the past 2 decades, with 5-year overall survival reaching 57% during 2002 to 2008 for patients with AA unresponsive to initial IST. Exclusion of hypocellular myelodysplastic syndrome and constitutional BM failure masquerading as apparent idiopathic AA should be done in conjunction with centers of excellence. Hematopoietic stem cell transplantation is indicated if refractory AA patients are fit and have a suitably matched donor, either a sibling (>40-50 years) or unrelated donor. Patients lacking a fully matched donor should be considered for a second course of antithymocyte globulin plus cyclosporin, although response in the refractory setting is only ∼30% to 35%. Response may also occur with alemtuzumab or the thrombopoietin mimetic eltrombopag in refractory AA. The emerging data for alternate donor (cord or haploidentical) transplantation in AA has provided additional therapeutic choices to consider in refractory disease.
authors: 1King's College Hospital and.
authors: Judith C W
authors: JC
authors: Marsh
authors: Austin G
authors: AG
authors: Kulasekararaj
mesh_terms: D000328:Adult; D000367:Age Factors; D000074323:Alemtuzumab; D064591:Allografts; D000741:Anemia, Aplastic / Q000401:mortality / Q000628:therapy*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000009:adverse effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001565:Benzoates / Q000009:adverse effects / Q000627:therapeutic use; D001855:Bone Marrow Diseases; D000080983:Bone Marrow Failure Disorders; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use; D018572:Disease-Free Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006457:Hemoglobinuria, Paroxysmal / Q000209:etiology / Q000401:mortality / Q000628:therapy; D006801:Humans; D006834:Hydrazines / Q000009:adverse effects / Q000627:therapeutic use; D007165:Immunosuppression Therapy / Q000009:adverse effects / Q000379:methods; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use; D035781:Siblings; D015996:Survival Rate; D061349:Unrelated Donors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum; D000970:Antineoplastic Agents; D001565:Benzoates; D006834:Hydrazines; D007166:Immunosuppressive Agents; D011720:Pyrazoles; D000074323:Alemtuzumab; D016572:Cyclosporine; C520809:eltrombopag