Myelodysplastic syndromes (MDS) encompass a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, peripheral blood cytopenias, and a risk of progression to acute myeloid leukaemia (AML). These disorders predominantly affect older adults, with a median age at diagnosis of 70-75 years.
Aetiology and Pathophysiology
MDS arises from genetic mutations in hematopoietic stem cells.Around 90% of cases are primary with the remaining 10% secondary to causes such as chemotherapy and radiotherapy. Secondary MDS typically develops around 5 years post-treatment.The key pathophysiological feature of MDS is ineffective hematopoiesis leading to peripheral cytopenias despite a typically hypercellular bone marrow. The exact mechanisms are still not entirely understood, but they likely involve a combination of increased apoptosis, abnormal differentiation, and immune dysregulation.
Clinical Features
MDS can present with various symptoms related to the underlying cytopenias. Common presentations include fatigue, weakness, and pallor due to anaemia; recurrent infections due to neutropenia; and easy bruising or bleeding due to thrombocytopenia. Some patients may be asymptomatic and are diagnosed incidentally on routine blood counts.
Diagnosis
The diagnosis of MDS is based on peripheral blood counts, bone marrow examination, and cytogenetic analysis. Bone marrow biopsy typically shows dysplastic changes in hematopoietic cells and a varying degree of blasts. Cytogenetic analysis can identify specific chromosomal abnormalities that may have prognostic implications.
Myelodysplasia may progress to acute myeloid leukaemia. Look out for the presence of blast cells if patient seems to get worse. ≥20% blasts in the peripheral blood or bone marrow is diagnostic according to WHO classification.
Treatment
Treatment of MDS depends on the subtype of MDS, the patient's age and overall health, and the severity of symptoms. Options include supportive care (e.g., blood transfusions, growth factors), disease-modifying therapy (e.g., hypomethylating agents, lenalidomide), immunosuppressive therapy, and hematopoietic stem cell transplantation. The latter is the only potentially curative option but is limited by the patient's age and comorbidities.