myelodysplastic

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal bone marrow disorders characterized by ineffective hematopoiesis, dysplasia of one or more myeloid cell lines, and peripheral blood cytopenias. They most often affect older adults and carry a risk of progression to acute myeloid leukemia (AML).

Pathophysiology and features

MDS arise from acquired mutations in hematopoietic stem cells that disrupt normal maturation and survival of blood cells. Common genetic changes involve splicing factors (such as SF3B1), epigenetic regulators (including TET2, DNMT3A, ASXL1), and various chromosomal abnormalities (for example, del(5q), monosomy 7, or complex karyotypes). The bone marrow is frequently hypercellular, with dysplastic changes in one or more lineages and variable excess of blasts. Ring sideroblasts occur in some subtypes, especially with SF3B1 mutations. Patients may have anemia, thrombocytopenia, or neutropenia, leading to fatigue, bruising, infections, and bleeding.

Diagnosis and classification

Diagnosis relies on complete blood counts, examination of the peripheral blood and bone marrow, cytogenetic analysis, and molecular testing. The World Health Organization (WHO) system classifies MDS into subtypes based on dysplasia, blast percentage, and specific genetic or morphologic features. Prognosis is commonly assessed with the International Prognostic Scoring System–Revised (IPSS-R), which uses cytopenias, marrow blast count, and cytogenetics to assign risk from very low to very high. Molecular data are increasingly incorporated into risk stratification.

Management

Treatment is risk-adapted. Low-risk disease emphasizes symptom management and quality of life: red blood cell transfusions, iron chelation for iron overload, erythropoiesis-stimulating agents, and, in selected cases, immunosuppressive therapy. High-risk disease uses disease-modifying strategies such as hypomethylating agents (azacitidine, decitabine) and consideration of allogeneic stem cell transplantation for eligible patients. Lenalidomide is particularly effective in those with a 5q deletion. Supportive care and participation in clinical trials remain important components of care.