Aplastic anemia

Most acquired aplastic anemia is the result of immune-mediated destruction of hematopoietic stem cells causing pancytopenia and an empty bone marrow, which can be successfully treated with either immunosuppressive therapy or hematopoietic stem-cell transplantation.

In aplastic anemia, oligoclonally expanded cytotoxic T cells induce apoptosis of hematopoietic progenitors. T-bet, a transcription factor that binds to the interferon-gamma promoter region, is upregulated in aplastic anemia T cells. Regulatory T cells are significantly reduced in patients' peripheral blood and in an aplastic anemia murine model, infusion of regulatory T cells ameliorates disease progression. In a minority of cases, loss-of-function mutations in telomerase complex genes may underlie disease development. Long-term survival, once strongly linked to response to immunosuppressive therapy, can now be achieved even among nonresponders due to significant advances in supportive care and better salvage treatments.

Evidence has accumulated in the recent years further corroborating an immune-mediated process underlying aplastic anemia pathogenesis. Hematopoietic stem-cell transplantation from a matched sibling donor is preferred for children and young adults with severe aplastic anemia, and immunosuppressive therapy is employed when hematopoietic stem-cell transplantation is not feasible due to age, lack of a histocompatible sibling, co-morbidities, or by patient choice.