Makindo Medical Notes

Related Subjects: |Iron deficiency Anaemia |Haemolytic anaemia |Macrocytic anaemia |Megaloblastic anaemia |Microcytic anaemia |Myelodysplasia

🧬 Malignant haematological condition characterised by ineffective haematopoiesis, cytopenias, and a risk of transformation into acute myeloid leukaemia (AML).
Key Point: Median survival is < 2 years in many subtypes, with infection and bleeding being the most common causes of death. ⚠️

📖 About

• Myelodysplastic syndrome (MDS) is a pre-leukaemic clonal disorder of dysplastic haemopoietic stem cells.
• Occurs mainly in older adults (rare under age 55).
• Progressive, with median survival depending on subtype and cytogenetic abnormalities.
• Transformation to AML occurs in 20–30% of patients.

🧬 Aetiology

• ~80% of patients have identifiable genetic/cytogenetic abnormalities.
• Maturation block → pancytopenia and ineffective haematopoiesis.
• Affects all myeloid lineages, with accumulation of blasts in the marrow.
• Marrow blast % = most important prognostic factor (≥20% = AML).

👶 Commoner in association with:

• Inherited bone marrow failure syndromes:
  • Down syndrome
  • Fanconi anaemia
  • Bloom syndrome
  • Ataxia telangiectasia
  • Shwachman-Diamond syndrome
• Secondary causes:
  • Previous chemotherapy or radiotherapy (therapy-related MDS)
  • Chemical exposure (e.g., benzene, pesticides)

📊 WHO Classification of MDS

🩺 Clinical Features: Progressive Bone Marrow Failure

• Anaemia: Fatigue, pallor, dyspnoea.
• Leucopenia: Recurrent infections (neutropenia + neutrophil dysfunction).
• Thrombocytopenia: Petechiae, purpura, mucosal bleeding.
• Bone marrow expansion: Rarely bone pain.
• Death is usually due to infection or haemorrhage.

🔍 Investigations

• FBC: Pancytopenia (low Hb, WCC, platelets).
• Blood film: Dysplastic features – macrocytosis, hypogranular neutrophils, pseudo–Pelger-Huët anomaly.
• Bone marrow biopsy: Hypercellular marrow with dysplasia. >20% blasts = AML.
• Genetics: Abnormalities of chromosomes 5q, 7q, or complex karyotypes.
• Biochemistry: No reticulocytosis (ineffective erythropoiesis).

💊 Management (Prognosis often poor)

• Supportive care: RBC and platelet transfusions, antibiotics.
• Erythropoietin: May improve anaemia in some patients.
• G-CSF: Can boost neutrophil counts, especially with EPO.
• Lenalidomide: Effective in MDS with isolated del(5q).
• Azacitidine: Hypomethylating agent, prolongs survival in high-risk MDS (~9 months benefit).
• Allogeneic stem cell transplant: Only curative option, suitable for young fit patients.
• Chemotherapy: Occasionally used in high-risk or transforming disease.

📚 References

• NCBI – Myelodysplastic Syndromes
• NHS – MDS Overview
• American Cancer Society – MDS