Chapter 16: Myelodysplastic Syndromes

Myelodysplastic syndromes represent a group of clonal bone marrow disorders where stem cells fail to develop into healthy blood cells, often resulting in a crowded marrow alongside low peripheral blood counts. This chapter delves into the underlying causes of these conditions, noting that they arise from genetic changes in multipotent cells, including chromosomal deletions and mutations in genes that regulate DNA methylation or RNA splicing. While many cases occur spontaneously, others are linked to previous cancer treatments, known as therapy-related disease. Patients, who are typically older with a median age of seventy, often experience severe exhaustion, persistent infections, or bleeding due to deficiencies in red cells, white cells, and platelets. Diagnostic procedures focus on identifying specific cell abnormalities, such as ring sideroblasts or strangely shaped neutrophils with the pseudo-Pelger deformity, and measuring the concentration of immature blast cells to determine the specific subtype. Prognosis is assessed using specialized scoring tools like the Revised International Prognostic Scoring System (IPSS-R), which help clinicians decide between conservative management and aggressive interventions based on karyotypes and cytopenias. For lower-risk patients, treatment may involve growth factors, blood transfusions, or targeted drugs like lenalidomide for those with specific genetic markers like the 5q deletion. In contrast, higher-risk cases may require powerful medications such as hypomethylating agents like azacitidine or a curative stem cell transplant. The text also highlights emerging concepts like Clonal Haemopoiesis of Indeterminate Potential (CHIP), where individuals carry mutations that increase their risk for both blood cancers and heart disease, as well as overlap disorders that combine features of bone marrow failure with excessive cell growth, such as chronic myelomonocytic leukaemia.