The optimal immunosuppressive therapy for aplastic anemia

Immunosuppressive treatment (IST) has been the most effective therapeutic modality for patients with aplastic anemia (AA) who are not eligible for allogeneic stem cell transplantation from HLA-matched siblings because of donor unavailability, old age, or comorbidities. The combination of horse anti-thymocyte globulin (ATG) with cyclosporine A (CsA) has shown satisfactory results for these patients, and so it has been regarded as the standard IST regimen. However, treatment failure including unresponsiveness, relapse, and occurrence of clonal evolution remains a major problem, although the results of IST have been improved in the past two decades. Many studies have been conducted to overcome these problems; however, they have yet to show any satisfactory results. This review will discuss immune-mediated pathophysiology of AA, which is associated with therapeutic targets of immunosuppressive agents and clinical outcomes of most commonly used IST regimens. Several trials to improve IST including the addition of other immunosuppressive agents or growth factors to standard IST regimen, comparison between horse ATG/CsA and rabbit ATG/CsA as first-line treatment, and promising alternative agents including alemtuzumab and eltrombopag will also be discussed, focusing on recently published literatures.