Changing the treatment paradigm in myelodysplastic syndromes.

The treatment algorithm for the patient with myelodysplastic syndrome (MDS) is in the process of being revitalized based on recent results of clinical trials. Historically, the goal for lower-risk patients was hematologic improvement, and disease modification was reserved for patients in the higher-risk category. Recent data now favor shifting emphasis away from supportive care alone and toward altering the disease course and prolonging survival, particularly in patients with intermediate-2 and high-risk disease. In addition, there is a greater appreciation for the significant morbidity and mortality resulting from MDS and increased efforts to improve quality of life while pursuing treatment. Immunomodulation with lenalidomide has yielded durable cytogenetic and hematologic responses and also has shown potential to alter disease course. Similarly, immunosuppression with antithymocyte globulin has shown sustained hematologic responses in selected patient subgroups. The methyltransferase inhibitors have demonstrated the ability to alter the natural history of disease and thus prolong time to leukemic transformation. In addition, azacitidine has shown the capacity to extend survival compared with the previous gold standard of conventional care regimens. With these new data, evaluation of treatment options should no longer focus on response rates as the sole endpoint but rather on time to leukemic transformation and survival. Timing of available therapies, including stem cell transplantation, should be incorporated into the new treatment paradigm, with end goals of prolonging survival and optimizing patient outcomes.