Haema 2012; 3(2): 158-174
by Vassiliki Pappa
Assistant Professor of Hematology, Medical School University of Athens, Second Department of Internal Medicine and Research Institute, Attikon University General Hospital, Athens, Greece
Abstract
The treatment of high risk MDS remains a major therapeutic challenge for the clinician. Although treatment options in the previous decades were very limited including AML type chemotherapy, bone marrow transplant in those cases that this was feasible or palliation, the advent of new therapies and more specifically of epigenetic treatments significantly broadened our therapeutic armamentarium. Epigenetic therapies include the DNA methyltransferase inhibitors and Histone Deacetylase Inhibitors. Within the group of DNA methyltransferase inhibitors 5- Azacytidine and decitabine have already been approved by the FDA for the treatment of MDS while 5- Azacytidine has also been approved in Europe for the treatment of intermediate-2 and high risk MDS and of AML with 20-30% blasts in the bone marrow. The approval of 5-azacytidine was based on the results of the AZA001 phase III randomized trial showing survival advantage in this group of patients. Decitabine however did not prove to offer survival advantage in the EORTC European phase III trial although demonstrating significant response rates and significantly longer progression free survival. Other epigenetic treatments like histone deacetylase inhibitors including valproic acid and vorinostat have been studied in small phase 1 and 2 studies with acceptable response rates that can further be increased in the context of combined treatments either with the methyltransferase inhibitors or with chemotherapy. The best combination of these new drugs, as well as the investigation of biological and clinical factors predictive of response remain to be elucidated in the near future.