Patients with low-risk MDS should be considered for therapy only if they are receiving frequent transfusions or their disease is showing progression with increasing severity of cytopenias, appearance of new cytogenetic abnormalities, rise in blasts, or multiple incidents of bleeding and infection. At this point, it is appropriate to consider placing such a patient on an experimental protocol. The hallmark of MDS is proliferation in the presence of excessive intramedullary programmed cell death. The presence of an excess of proinflammatory cytokines, especially tumor necrosis factor a (TNFa), an increase in microvessel density (MVD) with clear evidence of neoangiogenesis, and a poorly defined immunologic component have all been demonstrated in a subset of MDS patients. These biologic insights suggested experimental therapeutic approaches, including antiangiogenic therapies, anticytokines (especially anti-TNF), cytoprotection, and immune modulation.

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