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Treatment of adult myelodysplastic syndromes.

Patients with myelodysplastic syndromes (MDS) suffer from pancytopenia and are at substantial risk for progression to acute myeloid leukemia. The principal pathogenetic features of MDS are clonal evolution, ineffective hematopoiesis (apoptosis), and reduced cellular maturation. T-cell-mediated myelosupression may add to disease development in some patients. The disease is progressive and, for the majority of patients, the aim of treatment will be to improve blood values and quality of life. A minority of patients could be cured by allogeneic bone marrow transplantation, which results in an overall disease-free survival of about 40%. The value of autologous stem-cell transplantation is currently being investigated in clinical trials; this treatment may be found to be beneficial for some MDS patients. High-dose chemotherapy may lead to significant improvement and complete remission in about 50% of treated patients, but remission duration is usually short. Low-dose chemotherapy may also be used to improve peripheral blood values. Several new low-dose treatments are being tested at present. Growth factors can be used to improve both ineffective hematopoiesis and cytopenia. The value of treatment with growth factors alone for granulocytopoiesis is uncertain, whereas treatment for impaired erythropoiesis using erythropoietin alone or erythropoietin in combination with other growth factors seems more promising. Subgroups of MDS in which T-cell-mediated myelosuppression are present may respond favorably to cyclosporin A or antithymoglobulin. Antiapoptotic agents such as amifostine may improve blood values in some patients with MDS, but the value of this treatment is not yet clear. Increasing pathogenetic knowledge and better use of predictive models have resulted in some progress in MDS treatment. In the future, more effective treatments may result from further insights into the biology of the disease, the discovery of new therapeutic approaches, and the search for better ways to use existing therapeutic options.