Myelodysplastic syndromes

The myelodysplastic syndromes (MDS) are marrow failure syndromes characterized by cytopenias, blood cell dysmorphology, acquired clonal cytogenetic and molecular genetic mutations, and a risk of development of acute myeloid leukaemia. MDS may evolve in patients previously treated with cytotoxic chemotherapy or radiotherapy for a solid tumour, but most commonly arise de novo in patients over 60 years old. Most patients present with features of chronic anaemia or manifestations related to thrombocytopenia or infection. The diagnosis may be suggested by the presence of normocytic or macrocytic anaemia, with the peripheral blood smear showing dysplastic changes in red blood cells or neutrophils. Bone marrow aspirate and biopsy permits detailed cytogenetic study, which is critical for diagnostic classification and prognosis. Increasingly, molecular genetic assays (next-generation sequencing panels) aid in diagnosis and prognosis. The World Health Organization (WHO) classification recognizes various MDS subtypes based on the morphological appearance of the peripheral blood and bone marrow. These include MDS with excess blasts, MDS with deletion of the long arm of chromosome 5, and MDS with ring sideroblasts. Treatment is symptomatic in most cases. The only potentially curative treatment is allogeneic bone marrow transplantation, which is often precluded due to patients’ advanced age or comorbidity. Higher-risk patients may experience a survival benefit from treatment with the DNA hypomethylating agent azacitidine, and decitabine delays disease progression to acute myeloid leukaemia. Some patients with lower-risk disease may show a response to immunosuppression with antithymocyte globulin and ciclosporin. Patients with isolated chromosome 5q deletions and lower-risk disease may respond dramatically to lenalidomide, an immunomodulatory drug.