Overview
Definition
A group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, cytopenias, dysplastic bone marrow morphology, and a high risk of transformation to Acute Myelogenous Leukemia.
Epidemiology
Primarily a disease of the elderly (median age ~70). More common in patients previously treated with chemotherapy/radiation (therapy-related MDS).
Etiology & Risk Factors
- Acquired somatic mutations in hematopoietic stem cells (SF3B1, TET2, ASXL1, TP53)
- Environmental exposures (benzene, radiation)
Clinical Symptoms
- Anemia symptoms (fatigue, pallor)
- Thrombocytopenic symptoms (petechiae, easy bruising)
- Neutropenic symptoms (recurrent infections)
Clinical Approach
Diagnosis
- Persistent cytopenias (anemia, leukopenia, thrombocytopenia)
- Peripheral blood smear showing dysplastic cells (e.g., Pelger-Huët anomaly: bilobed neutrophils)
- Bone marrow biopsy showing hypercellular marrow with dysplastic lineages and <20% myeloblasts
Management
- Supportive care: Blood and platelet transfusions, erythropoietin-stimulating agents (ESAs)
- Luspatercept for MDS with ring sideroblasts
- Hypomethylating agents (Azacitidine, Decitabine) for high-risk MDS
- Allogeneic stem cell transplant (young, high-risk patients)
Complications
- Severe infection / Sepsis
- Life-threatening hemorrhage
- Transformation to Acute Myelogenous Leukemia (AML)