Thalidomide in multiple myeloma, myelodysplastic syndromes and histiocytosis. Analysis of clinical results and of surrogate angiogenesis markers

Background: Thalidomide, as a single agent, has been recently found to indu ce a clinical response in one third of refractory or relapsed myeloma patie nts. Although it has been reported that thalidomide significantly inhibits angiogenesis, it is still unclear whether its clinical effect is mediated, at least in part, by its anti-angiogenic properties. Patients and methods: We evaluated thalidomide as a single agent in myeloma , myelodysplastic syndromes (MDS) and histiocytosis, i.e. hematological dis eases characterized by increased angiogenesis, and measured prospectively a number of surrogate angiogenesis markers. Results: Clinical responses were observed in 7 of 17 myeloma and 2 of 5 MDS patients. The histiocytosis patient had a partial response. At the time of the best clinical response, plasma levels of angiogenic growth factors, va scular endothelial growth factor (VEGF) and basic-fibroblast growth factor (b-FGF), were significantly decreased, and flow cytometry indicated a decre ase of activated endothelial cells in the bone marrow of responding MDS pat ients. Conclusions: These observations confirm thalidomide efficacy in myeloma, su ggest a possible use in MDS and histiocytosis and may contribute to the pre diction of clinical response and to understanding the mechanism of thalidom ide's action.