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Myelodysplastic syndromes

The myelodysplastic syndromes (MDS, formerly known as "preleukemia") are a diverse collection of haematological conditions united by ineffective production of blood cells and varying risks of transformation to acute myelogenous leukemia. Anemia requiring chronic blood transfusion is frequently present. more...

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Medicines

Signs and symptoms

Abnormalities include:

  • neutropenia, anemia and thrombocytopenia (low cell counts of white & red blood cells and platelets, respectively)
  • abnormal granules in cells, abnormal nuclear shape and size
  • chromosomal abnormalities, including chromosomal translocations.

Symptoms of myelodysplastic conditions:

  • Anemia - chronic tiredness, shortness of breath, chilled sensation, sometimes chest pain
  • Neutropenia (low white cell count) - increased susceptibility to infection
  • Thrombocytopenia (low platelet count) - increased susceptibility to bleeding

All these conditions have an increased risk of developing acute leukaemia, which is notoriously resistant to treatment ("secondary leukaemia").

Diagnosis

Investigation:

  • Full blood count and examination of blood film
  • Bone marrow aspirate and biopsy with examination by an experience hematopathologist
  • Cytogenetics or chromosomal studies. This is performed on the bone marrow aspirate.

Pathophysiology

MDS is due to genetic defects in the multi-potent blood stem cell of the bone marrow. Most of these are not yet described. Differentiation of the abnormal cells is impaired. Clonal expansion of the abnormal cells lead to production of abnormal cells and decreased production of normal bone marrow products.

Bleeding (due to lack of platelets) or infection (due to lack of white blood cells) is common in the majority of MDS patients. In about 25-35% of patients there is a further genetic mutation in one of the abnormal blood stem cells which eventually results in acute leukemia. The progression of MDS to leukemia is a good example of the multi-step theory of carcinogenesis in which a series of mutations occur in an initially normal cell and transform it into a cancer cell.

Types and classification

French-American-British (FAB) classification

In 1974 and 1975 a group of pathologists from France, the United States, and Britain met and deliberated and derived the first widely used classification of these diseases. This French-American-British (FAB) classification was published in 1976 and revised in 1982. Cases were classified into 5 categories: (ICD-O codes are provided where available)

  • (M9980/3) Refractory anemia (RA) - characterized by less than 5% primitive blood cells (myeloblasts) in the bone marrow and pathological abnormalities primarily seen in red cell precursors;
  • (M9982/3) Refractory anemia with ringed sideroblasts (RARS) - also characterized by less than 5% myeloblasts in the bone marrow, but distinguished by the presence of 15% or greater red cell precursors in the marrow being abnormal iron-stuffed cells called "ringed sideroblasts";
  • (M9983/3) Refractory anemia with excess blasts (RAEB) - characterized by 5-19% myeloblasts in the marrow;
  • (M9984/3) Refractory anemia with excess blasts in transformation (RAEB-T) - characterized by 20-29% myeloblasts in the marrow (30% blasts is defined as acute myeloid leukemia);
  • (M9945/3) Chronic myelomonocytic leukaemia (CMML) - not to be confused with chronic myelogenous leukemia or CML - characterized by less than 20% myeloblasts in the bone marrow and greater than 1000 * 109/uL monocytes (a type of white blood cell) circulating in the peripheral blood.

A table comparing these is available from the Cleveland Clinic.

Read more at Wikipedia.org


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