Thalidomide therapy for myelodysplastic syndromes: current status and future perspectives.
Thalidomide exerts in vitro heterogeneous biological effects on hematopoiesis which have supported its possible use in treating myelodysplastic syndromes (MDS). Some recent clinical trials have confirmed that thalidomide may improve anemia and, less frequently, other cytopenias, in a proportion of younger patients with low-risk MDS (11-56%, on intention-to-treat analysis). Of interest, erythroid responses may be achieved also in transfusion-dependent subjects with high serum levels of endogenous erythropoietin, a subset of MDS patients with little chance of responding to recombinant erythropoietin, alone or in combination with G-CSF. Older patients, however, often do not tolerate the drug even at very low doses. How thalidomide acts in MDS is not clear. Some data suggest several mechanisms possibly involving stimulation of erythropoiesis through activation of physiological compensative mechanisms and reduction of apoptosis. The combination of thalidomide with other molecules active on hematopoiesis and the use of more effective and less toxic analogs are currently under clinical investigation.
Musto
Pellegrino
P
Unit of Hematology and Stem Cell Transplantation, IRCCS Casa Sollievo della Sofferenza Hospital, 71013 S. Giovanni Rotondo, Italy. p.musto@tin.it
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004921:Erythropoietin / Q000097:blood; D016222:Fibroblast Growth Factor 2 / Q000097:blood / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000097:blood; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D013792:Thalidomide / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000187:drug effects
D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D004921:Erythropoietin; D013792:Thalidomide; D017228:Hepatocyte Growth Factor