The myelodysplastic syndromes (MDS) are clonal bone marrow (BM) stem cell disease(s), characterized by abnormal hematopoiesis, with anemia (95%) and/or other cytopenias. The pathogenesis is based on genetics and inflammation of aging (inflammaging). The median age of onset is 74yr, with increasing incidence with age. Patients are classified as having a lower (LR-MDS) or higher risk disease (HR-MDS), and leukemic transformation occurs in 20%-60%.

We will cover new aspects like quality of life (QoL), novel genetic information, will briefly touch the emerging field of inflammaging, describe new tools for (early) diagnosis, the new classifications, and finally will address MDS treatment. We will skip aspects such as epidemiology, clinical picture and cytogenetics.

Over the last decade QoL has become important in MDS, to study and improve – we will show some data. Genetics is an integral part of evaluation, with at least one mutation in 90% of MDS patients, but as more information is obtained it has become clear that the field is quite complex. The pathogenesis is carefully investigated and inflammation of aging (inflammaging) appears to play an important role.

Diagnosis of MDS has been recognized as a challenge. The introduction of new tools, such as genetic and digital medicine improve the process, make it more accurate, less invasive, and hopefully may identify individuals at risk.

Several new MDS classifications (and guidelines) have been proposed over the last couple of years. We will focus on the new IPSS-Molecular model, and will summarize the 5th WHO and ICC classifications.

RBC transfusions and erythropoietin (EPO) remain the 1st line treatment for anemia in lower-risk MDS. EPO is safe and might delay the need for RBC transfusions. A recent EUMDS study suggests a prolonged survival with EPO. Lenalidomide remains effective for MDS with del(5q) (50% response), but also somewhat effective (27%) in non-del(5q) patients. Luspatercept appears as an effective second-line (maybe 1st ?) agent. Several experimental agents are investigated, including oral azacytidine, imetelstat, a pyruvate-kinase activator and roxadustat. For thrombocytopenia two agents, romiplostim and eltrombopag, were shown to be effective. However, due to safety concerns their development has been stopped.

Treatment of higher-risk MDS is still based on hypomethylating agents (HMA) as the standard 1st line treatment, but attempts are ongoing to overcome the barrier of 50% response rate and less than 2 years response duration. Younger patients may respond to antileukemic treatment with or without transplant. Ways to improve the HMA effect include treating the HMA-related complications; modified HMA formulation; combinations of HMA with other agents (venetoclax appears to be the frontrunner), novel agents and targeted molecules.