Idiopathic Aplastic Anemia

Aplastic anemia is a rare disease characterized by presenting bone marrow failure and pancytopenia, with no trace of myeloproliferative or fibrotic processes. It confers a significant risk for morbidity and death due to its progressive natural history and complications related to suboptimal therapy. The pathophysiology is immune-mediated in most cases, with activated type 1 cytotoxic T cells implicated. The molecular basis of the aberrant immune response and deficiencies in hematopoietic cells is now being defined genetically; examples are telomere repair gene mutations in the target cells and dysregulated T-cell activation pathways. Establishing an accurate etiology of aplastic anemia is challenging but also critical to appropriate management, especially differentiating between acquired and inherited forms of the disease. Aplastic anemia can be cured or alleviated by stem-cell transplantation or immunosuppressive drug therapy. Immunosuppression with antithymocyte globulins (ATGs) and cyclosporine effectively restores blood-cell production in most patients, but relapse and especially the evolution of clonal hematologic diseases remain problematic. Allogeneic stem-cell transplant from histocompatible sibling donors is curative in the great majority of young patients with severe aplastic anemia; the major challenge is extending the benefits of transplantation to patients who are older or who lack family donors.