Thalidomide and thrombosis.

Department of Hematology, San Bortolo Hospital Via Rodolfi – 36100 Vicenza (Italy) Tel. 39 0444 99 3626, Fax 39 0444 92 0708 E-Mail [email protected] Thalidomide is a glutamic acid derivative that exerts potent anti-angiogenic activity, modulation of T-cell activity and direct effects on tumour cells and their microenvironment. For its anti-inflammatory activity, mainly due to inhibition of TNFproduction, this agent is used to treat leprosy (registered use), lupus erythematosus, atopic dermatitis and Behçet’s disease. The anti-angiogenic activity of thalidomide suggested its use for the treatment of both solid and hematologic malignancies. Elevated levels of proangiogenic factors, particularly vascular endothelial growth factor (VEGF) have been associated with a poor prognosis in leukemias, multiple myeloma and NHL. In addition, a direct relationship between VEGF production and leukemic blasts and malignant plasma cells proliferation has been established, thus anti-VEGF agents are being evaluated in many protocols. The anti-angiogenic activity of the drug may be due to a reduction of both VEGF and b-FGF (basic fibroblast growth factor) levels, although disconcordant findings have been reported [1]. Thalidomide was shown to be effective in relapsed or refractory multiple myeloma and its role as part of the initial treatment armamentarium is under investigation. The anti-myeloma effect is mediated by several mechanisms: induction of G1 growth arrest/apoptosis by inhibiting NFB and activating caspase 8; inhibition of adhesion of myeloma cells to bone marrow stromal cells; inhibition of secretion of cytokines (TNF, IL-6, IL-1 ); induction of T cell and NK cell anti-myeloma immunity and inhibition of angiogenesis. Incidence of Thalidomide-Associated Thrombosis