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Myelodysplastic syndrome

The myelodysplastic syndromes are a collection of haematological conditions including:

  • Refractory anaemia (RA)

  • Refractory anaemia with ring sideroblasts (RARS)

  • Refractory anaemia with excess of blasts (RAEB)

  • Chronic myelomonocytic leukaemia (CMML) - not to be confused with CML

All the conditions show abnormalities in the production of one or more of the cellular components of blood (red cells, white cells (other than lymphocytes) and platelets (or their progenitor cells, megakaryocytes).

These abnormalities include:

  • neutropenia, anaemia and thrombocytopenia (low cell counts of each)

  • abnormal granules in cells, abnormal nuclear shape and size

  • chromosomal abnormalities, including chromosomal translocations.

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It is estimated that 7,000 to 12,000 new cases of myelodysplastic syndrome are diagnosed each year in the U.S. These are mostly conditions of the elderly. However, there is an increased risk in those people who have had chemotherapy for other tumors.

Signs and symptoms

  • Anaemia - chronic tiredness (in this condition blood transfusion is the only effective treatment, which can carry on for years)

  • Neutropenia (low white cell count) - increased susceptibility to infection

  • Thrombocytopenia (low platelet count) - increased susceptibility to bleeding

Because the cellular function is impaired the effects of low cell counts may be greater than in other conditions with a similar cell count be less impairment of normal function.

All these conditions have an increased risk of developing acute leukaemia, which is notoriously resistant to treatment ("secondary leukaemia"). In RA and RARS the risk is relatively low and the condtion may persist for many years (eg 10). In RAEB and CMML the time course is typically quicker.

Clinical suspicion

Normocytic anemia & reticulocytopenia not diagnosed conventionally will require a bone marrow aspirate and subsequently a bone marrow biopsy OR macrocytic anemia not found to be due to folate or B12 deficiencies. More advanced cases may present with evidence of myelodysplasia.


Required investigations include:

  • Full blood count and examination of blood film

  • Bone marrow aspirate

  • In some cases: chromosome studies.

Refractory anemia (RA)

CBC: Macrocytic anemia with reticulocytopenia.

Bone marrow: The myeloid and megakaryocytic series in the bone marrow appear normal, but megaloblastoid erythroid hyperplasia is present. Dysplasia is usually minimal. 

Refractory anemia with ringed sideroblasts (RAS)

The blood and marrow are identical to those in patients with RA, except that >15% of marrow red cell precursors are ringed sideroblasts.

Refractory anemia with excess blasts (RAEB)

Clinical suspicion: There is significant evidence of disordered myelopoiesis and megakaryocytopoiesis in addition to abnormal erythropoiesis.

Diagnosis: The marrow contains 5% to 20% myeloid blasts, and 1% to 5% of blasts may circulate in the blood.

Refractory anemia with excess blasts in transformation (RAEB-t)

Clinical suspicion: This is a panmyelosis

Diagnosis: 20% to 30% of marrow cells are blasts and >5% blasts are seen in the blood.  Auer rods may be seen.

Chronic myelomonocytic leukemia (CMML)

Clinical suspicion: Hepatosplenomegaly may be present.

Mild thrombocytopenia & mild anemia associated with morphologically normal megakaryocytes & red cell precursors in the marrow may be present.

Diagnosis: The marrow contains 5% to 20% blasts, and the circulating monocyte count is >1000 per cubic millimeter.


  • No treatment (watch and wait)

  • Conservative (eg periodic blood transfusion)

  • Chemotherapy (although often patients do not tolerate chemotherapy well).

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