 Defibrotide DF is a novel orally bioavailable polydisperse oligonucleotide with anti-thrombotic and anti-adhesive effects, which has been shown to be active in various microangiopathies, including the treatment and prophylaxis of veno-occlusive disease. While DF has minimal inhibitory effect on multiple myeloma MM in cell isolates, it showed single agent activity on human MM xenografts in SCIDNOD mice and markedly increased responsiveness of MM to cytotoxic agents, including melphalan, cyclophosphamide and dexamethasone in the same models. DF might thus enhance the response rate of Melphalan, Prednisone and Thalidomide, while protecting against the prothrombotic state seen with this combination in the treatment of MM. In this multicenter, open label, non-randomised phase III trial, dosing safety and efficacy of melphalan, prednisone, thalidomide, and DF MPTD were determined in pts with relapsedrefractory MM. 