Aplastic anaemia: pathogenetic mechanisms and treatment with special reference to immunomodulation

Aplastic anaemia (AA) has been defined as a syndrome in which the presence of pancytopenia is accompanied by marrow hypocellularity. Ample laboratory data and clinical observations continue to make immune mediation of bone-marrow failure an attractive hypothesis. Recent progress in the practice of bone-marrow transplantation has led to a survival rate of approximately 80% in the best cases, but such a treatment is only amenable in young patients (less than 45-50 years) with HLA-identical bone-marrow donors. Anti-lymphocyte and thymocyte globulin treatment has been surprisingly effective for AA, resulting in transfusion independence in 40-80% of patients. The mechanism of action is unknown, although effects on immunosuppression appear to be the most likely candidates. Long-term results for patients receiving cyclosporin A treatment will soon be available, and preliminary data show an effect similar to that of antithymocyte globulin. In contrast to successful bone-marrow transplantation, improvement following immunomodulation leaves quantitative abnormalities in all haematopoietic cell lines, and patients are prone to develop clonal (malignant) disease.