Management of the refractory aplastic anemia patient: what are the options?

TY - JOUR

T1 - Management of the refractory aplastic anemia patient

T2 - what are the options?

AU - Marsh, Judith C. W.

AU - Kulasekararaj, Austin G.

PY - 2013/11

Y1 - 2013/11

N2 - 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 similar to 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.

AB - 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 similar to 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.

KW - CORD BLOOD TRANSPLANTATION

KW - STEM-CELL TRANSPLANTATION

KW - ANTI-THYMOCYTE GLOBULIN

KW - HIGH-DOSE CYCLOPHOSPHAMIDE

KW - SAA WORKING PARTY

KW - IMMUNOSUPPRESSIVE THERAPY

KW - ANTITHYMOCYTE GLOBULIN

KW - ANTILYMPHOCYTE GLOBULIN

KW - MARROW FAILURE

KW - ALTERNATIVE DONOR

U2 - 10.1182/blood-2013-05-498279

DO - 10.1182/blood-2013-05-498279

M3 - Article

SN - 1528-0020

VL - 122

SP - 3561

EP - 3567

JO - Blood

JF - Blood

IS - 22

ER -