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• W2040384014 abstract "The myelodysplastic syndromes (MDS) continue to pose conceptual and practical conundrums because of their heterogeneity and therapeutic challenges. They are not restricted to the presence of clonal cells that are prone to excessive proliferation and premature apoptosis. In MDS the bone marrow microenvironment also is abnormal and exhibits an excess of proinflammatory cytokines, especially tumor necrosis factor (TNF), neoangiogenesis, and poorly defined immune defects. Thalidomide, a drug with anti-TNF, antiangiogenic, and immunomodulatory activities, and other agents with anti-TNF effects, such as pentoxifylline, etanercept, and infliximab, have produced hematologic improvement in 20% to 40% of patients. These agents may provide effective therapy for a subset of lower-risk MDS patients, even if the drugs target the bone marrow microenvironment predominantly. However, in higher-risk MDS patients, especially those with more than 10% blasts, it is important to eliminate abnormal cell clones; drugs used for this purpose have included arsenic trioxide, topotecan, the farnesyl transferase inhibitor tipifarnib, and demethylating agents, such as 5-azacytidine and decitabine. To increase the therapeutic index, a combination strategy may be preferable for higher-risk MDS patients, in whom the seed (clone) and the soil (bone marrow microenvironment) must be targeted simultaneously. The challenge is to recognize the subset that is likely to respond to a given drug so that patients can be preselected for therapy." @default.
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• W2040384014 date "2004-04-01" @default.
• W2040384014 modified "2023-09-27" @default.
• W2040384014 title "Targeted therapies in myelodysplastic syndromes: ASH 2003 review" @default.
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• W2040384014 doi "https://doi.org/10.1053/j.seminhematol.2004.02.003" @default.
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