Latest Developments

The past several years have brought exciting new developments in the treatment and understanding of myelodysplastic syndromes (MDS). A better understanding of the biology of the disease has provided new molecular targets for inhibiting the genesis and progression of myelodysplasia. The result of these discoveries has been new treatments and widespread clinical trials that have been met with enthusiastic participation.1

The ongoing clinical trials aim to improve current treatment options for MDS as well as test and perfect novel therapies. Growth factor investigation is a good example of these continuing efforts. Although growth factors like granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been shown to improve neutrophil production, they have not been shown to decrease infection rates or risks.2

Consequently, researchers are working to improve the effects of these hormones and develop new ones. For instance, currently there is not a growth factor for stimulating platelet production, but ongoing studies of interleukin-11, interleukin-6 and thrombopoietin have shown promising results.3

Additionally, ongoing research aims to improve the performance of the agents already in use, including thalidomide, lenalidomide, arsenic trioxide, the retinoids, interferons, farnesyl transferase inhibitors, infliximab, amifostine, valproic acid, and vitamin D.4 The broad aim of this research is to make existing therapies more effective and better tolerated so that they can be used for more patients.5

Attempts to make hematopoietic stem-cell transplantation available to a broader selection of older patients also continue, as investigators further develop autologous transplantation, peripheral blood stem-cell transplants, and nonmyeloablative transplants.4

Besides these existing treatments, there are novel therapies that seek to achieve the primary goal of all MDS treatment and research — to restore normal hematopoiesis.5 Therapies that target epigenetic changes are of particular interest. Problematic cytosine methylation has been well established as one of the most common epigenetic changes in cancer, which makes targeting DNA methylation a very appealing therapeutic strategy.1

DNA methyltransferase inhibitors (or hypomethylating agents) have already been shown to produce responses, but their method of action is still under investigation.1 Histone deacetylase (HDAC) inhibitors also have shown promise, and many of these agents are under clinical investigation.1 Interest in HDACs and their potential for addressing myeloid cancers originated in the observation that butyrate derivatives and polar planar compounds influence differentiation.1

Currently two methylating agents, azacytidine (FDA-approved) and decitabine (in development), have demonstrated the most promise for treating high-risk MDS patients. New research investigating combinations of these agents with HDACs aims to make them even more effective.6