The Immune-mediated Pathogenesis and Treatment of Aplastic Anemia

Aplastic anemia is an immune-mediated disorder in most cases. The suppression of hematopoiesis by CD8+ T cells and also the overproduction of interferon(IFN)-γ and tumor necrosis factor (TNF)-α due to the Th1 response were demonstrated. Aplastic anemia patients with HLA-DRB1*1501 and oligoclonality of the T-cell repertoire in the peripheral blood showed immunosuppressive therapy (IST), cyclosporine A (CyA) dependence. A minor population of paroxysmal nocturnal hemoglobinuria (PNH)-type blood cells, CD55-CD59-, predicts the response to IST. In patients with aplastic anemia, CD3+,CD4+ IL-17-producing T (Th17) cells were increased in the peripheral blood, whereas CD4+,CD25+,Foxp3+ regulatory T (Treg) cells, were decreased, suggesting the regulation of hematopoiesis by these cells in aplastic anemia. The standard immunosuppressive regimen for aplastic anemia has been horse antithymocyte globulin (hATG) and CyA, generating a hematologic response in 60-70% of patients receiving it as the first-line therapy. However, hATG was withdrawn from the market, and rabbit ATG (rATG) is the only formulation currently available in Japan. There are only limited data on rATG as the first-line therapy, and the clinical efficiency of rATG has not been established. Relapse after the initial response to IST is frequent, 30-50%. A very slow tapering of CyA is recommended. Hematopoietic stem cell transplantation (HSCT) is the treatment with the highest probability of cure in patients under 40 years old.