Advances in the therapy of the myelodysplastic syndromes.

Abstract

The study of the proliferation and differentiation of the MDS clone at the molecular level, including the details of apoptosis, may hopefully lead to more effective differentiation-induction/antiapoptotic agents. The study of the cytokines at the cellular/molecular level may lead to more effective trails of combination therapy with differentiation-induction agents, chemotherapy, and/or early-acting cytokines. Further phenotypic characterization of the MDS clone may lead to negative selection of these cells or positive selection of normal stem cells as part of an autotransplant strategy, as is presently being done in chronic-phase chronic myeologenous leukemia. The use of agents such as the topoisomerase I inhibitors (e.g., topotecan), which have mechanisms of action disparate from agents already used in MDS, may increase the efficacy of chemotherapy for MDS. The further clinical refinements in reducing treatment-related mortality and the study of T cells at the molecular level may hopefully lead to improvement in the prevention and therapy of graft-versus-host disease, in turn increasing the upper age limit of allogeneic BMT for MDS and increasing the feasibility of matched unrelated allogeneic BMT. At present, we can tailor the approach to a MDS patient based on his or her IPSS risk stratification, degree of cytopenia, and age, as outlined in Figure 2. At present, we can tailor the approach to a MDS patient based on his or her IPSS risk stratification, degree of cytopenia, and age, as outlined in Figure 2.