Pathophysiology and treatment of aplastic anemia.

Aplastic anemia (AA) is a rare hematological disease characterized by peripheral blood pancytopenia and a hypocellular bone marrow in which normal hematopoietic tissue is replaced by fatty marrow. There is strong in vitro and in vivo evidence suggesting an immunologic mechanism for hematopoietic suppression in the majority of patients with AA. Interferon-gamma and tumor necrosis factor-alpha are considered as soluble mediators of bone marrow (BM) suppression in AA. The events triggering the aberrant immune response are less clear but some viruses and drug metabolites may lead to autoimmune destruction of hematopoietic cells. Patients with severe AA who are younger than 35 to 45 years and who have an HLA-identical sibling donor have a 60-80% chance of being cured by allogeneic BM transplantation. In patients surviving more than two years, chronic graftversus-host disease is the major cause of morbidity and mortality and a solid-tumor malignancy may develop in a few patients. Patients without HLA-identical BM donors and patients older than 35 to 45 years are candidates for combined immunosuppressive treatment with antithymocyte globulin, methylpredisolone and cyclosporine, leading to hematological responses in 70-80% of patients. One has to consider, however, that a significant proportion of these patients will develop further clonal hematological disorders such as paroxysmal nocturnal hemoglobinuria and myelodysplastic syndrome.