myelodysplastiske

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal bone‑marrow disorders characterized by ineffective hematopoiesis, dysplasia in one or more blood cell lineages, and peripheral cytopenias that increase the risk of progression to acute myeloid leukemia (AML). Eponymously referred to as “myelodysplastiske” in Danish contexts, MDS affects predominantly older adults, with incidence rising markedly after 65 years of age.

The aetiology of MDS is multifactorial. Age‑related genetic instability, exposure to alkylating agents, radiation, or benzene, as well as inherited bone‑marrow failure syndromes such as Fanconi anaemia or GATA2 deficiency, are recognized risk factors. Sporadic cases are often associated with somatic mutations in genes regulating DNA methylation, splicing, transcription, or tumor suppression (e.g., TET2, ASXL1, TP53, RUNX1).

Clinically, patients present with fatigue, infections, bleeding, or pallor, reflecting anemia, neutropenia, or thrombocytopenia. Physical signs include pallor, petechiae, and, less frequently, organomegaly. Hematologic evaluation reveals dysplastic cells—anisocytosis, poikilocytosis, leukoerythroblastic changes—in peripheral smears. Bone‑marrow aspirate and core biopsy demonstrate hypocellular or hypercellular marrow with dysplasia in one or multiple lineages and increased blasts.

Risk stratification relies on the World Health Organization (WHO) classification and the International Prognostic Scoring System (IPSS) or its revised versions (IPSS‑R, CPSS). Treatment is tailored to risk category: supportive care (transfusions, growth factors), disease‑modifying agents (hypomethylating agents like azacitidine or decitabine, lenalidomide for 5q‑deleted disease), allogeneic stem‑cell transplant for suitable candidates, or palliative management for advanced cytopenias. Clinical trials are exploring targeted therapies against mutant spliceosome components, epigenetic regulators, and immune checkpoints. Prognosis varies: low‑risk patients may have disease‑free intervals of several years, whereas high‑risk or TP53‑mutated cases often progress to AML within one year. Continued research into genomic profiling and novel therapeutics promises to refine prognostication and improve outcomes for patients with myelodysplastic syndromes.