An update on treatment of higher risk myelodysplastic syndromes.

INTRODUCTION: Myelodysplastic syndromes (MDS) are clonal stem cell disorders mostly affecting the elderly. They are classified into lower and higher risk MDS according to prognostic scoring systems. In higher risk patients, treatments should aim to modify the disease course by avoiding progression to acute myeloid leukemia and, therefore, to improve survival. Areas covered: Stem cell transplantation remains the only curative treatment when feasible, but this concerns a small minority of patients. Treatment is principally based on hypomethylating agents (HMAs). Our understanding of MDS biology has led to the development of drugs targeting key cellular processes such as apoptosis or posttranslational protein changes, microenvironment-like immunotherapy, and gene mutations. Currently, new drugs are mainly being tested in combination with HMAs in several clinical trials. Expert commentary: Significant advances have been made in the field of MDS, especially in molecular typing, which are improving our ability to offer patients risk-adapted therapies. The current challenge in the management of higher risk MDS is to improve outcome by combining classical HMAs with novel drugs.