1) Definition
Myelodysplastic Syndromes (MDS) are a group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis (impaired blood cell production), leading to peripheral blood cytopenias (anemia, neutropenia, and/or thrombocytopenia) and morphologic dysplasia (abnormal blood cell appearance) in one or more myeloid cell lines. MDS can progress to acute myeloid leukemia (AML) in approximately 20–30% of cases.
2) Causes and Risk Factors
MDS can be primary (de novo) or secondary:
- Primary MDS: Idiopathic, most common in elderly patients (>60 years).
- Secondary MDS: Associated with prior exposure to:
- Chemotherapy (alkylating agents, topoisomerase II inhibitors)
- Radiation therapy
- Environmental toxins (e.g., benzene)
- Congenital syndromes (e.g., Fanconi anemia, Diamond-Blackfan anemia)
Genetic mutations frequently involved include alterations in genes like TP53, TET2, ASXL1, SF3B1, and DNMT3A.
3) Symptoms
Symptoms result from cytopenias and may include:
- Anemia: Fatigue, pallor, dyspnea on exertion
- Neutropenia: Recurrent infections, fever
- Thrombocytopenia: Easy bruising, petechiae, mucosal bleeding
Systemic symptoms such as weight loss or fever are less common unless there is progression to AML.
4) Diagnosis
Diagnosis requires integration of clinical, laboratory, and morphologic data:
- CBC: Macrocytic anemia, leukopenia, and/or thrombocytopenia
- Peripheral smear: Dysplastic features (e.g., hypogranular neutrophils, oval macrocytes)
- Bone marrow biopsy: Hypercellular or hypocellular marrow with dysplasia in ≥1 myeloid lineage; blast count <20%
- Cytogenetics: Common abnormalities include del(5q), del(7q), monosomy 7, trisomy 8
- Molecular testing: Assesses mutations for prognostication
Diagnosis is formalized using WHO criteria and risk stratified via IPSS-R (Revised International Prognostic Scoring System).
5) Treatment Options
Treatment is risk-adapted:
Low-risk MDS (e.g., isolated del(5q), <5% blasts, fewer cytopenias):
- Supportive care: RBC/platelet transfusions, growth factors (EPO, G-CSF)
- Lenalidomide: Especially in del(5q) MDS
- Immunosuppressive therapy: For selected younger patients (e.g., ATG + cyclosporine)
High-risk MDS (≥5% blasts, complex karyotype, multiple cytopenias):
- Hypomethylating agents: Azacitidine or decitabine
- Allogeneic hematopoietic stem cell transplantation (HSCT): Only curative option; considered in eligible patients
- Clinical trials: For novel agents and targeted therapies
6) Prognosis
Prognosis is variable and depends on age, performance status, cytogenetics, blast percentage, and cytopenias.
- Low-risk MDS: Median survival of several years; low progression to AML
- High-risk MDS: Median survival <1.5 years; higher likelihood of transformation to AML
The IPSS-R categorizes patients into very low to very high risk, guiding therapeutic decisions.