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Acute Myeloid Leukaemia

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Overview

Acute myeloid leukaemia (AML) is a malignancy of the bone marrow characterised by the rapid and uncontrolled proliferation of myeloid precursor cells. This is usually the result of their development arresting (stopping) in the first stages of development leading to abnormal blood cells and accumulation in organs, particularly the liver and spleen.

AML can also occur secondary to chronic myeloid leukaemia (CML) and myeloproliferative disorders such as myelofibrosis (MF), polycythaemia rubra vera, and essential thrombocytosis.

Epidemiology

  • Most common leukaemia in adults
  • More common in patients >75 years
  • The median age of diagnosis is 76 years

Risk Factors

Example History

A 70-year-old man has lethargy and shortness of breath on exertion. On examination, he looks pale and has splenomegaly. He has a medical history of polycythaemia vera.

Investigations:

Haemoglobin:125 g/L(130 – 180 – g/L)
Platelets:80 x 109/L(150 – 450 x 109/L)
Mean cell volume (MCV):100.0 fL(76.0 – 98.0 fL)
White blood cells (WBC):41.0 x 109/L(3.0 – 10.0 x 109/L)
Neutrophils:1.00 x 109/L(2.00 – 7.00 x 109/L)
Lymphocytes:1.30 x 109/L(1.00 – 4.00 x 109/L)
Monocytes:0.23 x 109/L(0.20 – 0.80 x 109/L)
Eosinophils:0.00 x 109/L(0.00 – 0.40 x 109/L)
Blood film:Auer rods seen

Presentation

Symptoms can be due to bone marrow failure leading to anaemia, neutropenia, and thrombocytopenia, or due to organ infiltration:

  • Features of anaemia:
    • Shortness of breath
    • Fatigue
    • Pallor
  • Features of thrombocytopenia:
  • Features of neutropenia:
    • Frequent and severe infections
  • Constitutional symptoms:
  • Features due to AML cell infiltration at different sites:
    • Splenomegaly:
      • Due to both increased sequestration and infiltration
    • Bone pain
    • Generalised lymphadenopathy
    • Swelling of the gums

Differential Diagnoses

Chronic myeloid leukaemia (CML)

  • In CLL patients are usually asymptomatic, but in CML they may have anaemia, weight loss, and night sweats
  • Splenomegaly is more marked in CML compared to AML. In CML, it is often severe enough to cause abdominal discomfort
  • Blood film shows myeloid cells (e.g. granulocytes) at different stages of maturation and thrombocytosis unlike in AML which shows blasts and immature cells

Acute lymphoblastic leukaemia (ALL)

  • Usually seen in children <5 years
  • May be indistinguishable
  • Bone marrow biopsy and immunophenotyping can help differentiate

Investigations

All patients

  • Full blood count (FBC) and white cell differential:
    • Haemoglobin: low
    • MCV: may be raised
    • White cell count: raised
    • Neutrophils: low
    • Platelets: low
  • Blood film:
    • Auer rods or Phi bodies seen
    • ≥20% of cells are blasts on the film
    • Hypergranular promyelocytes with bilobed nuclei with Auer rods may be seen
  • Urea and electrolytes (U&Es):
  • Lactate dehydrogenase (LDH):
    • May be increased due to cell turnover
  • Bone marrow biopsy and trephine biopsy – diagnostic:
    • Shows ≥20% blasts and Auer rods
  • Flow cytometry:
    • Can detect myeloid antigens to aid diagnosis with the biopsy

Management

Overview

Treatment is performed on case-by-case bases and guided by an oncology multidisciplinary team. Chemotherapy, radiotherapy, surgery, and stem cell transplantation are often used.

Complications

  • Tumour lysis syndrome
  • Leukostasis – white cells block microvasculature leading to respiratory distress or neurological symptoms
  • Neutropenia – leads to frequent and severe infection
  • Pancytopenia – due to bone marrow infiltration

Prognosis

  • Factors associated with a poorer prognosis are:
    • Older age
    • White cell count >100,000 x 109/L
    • Emergence of leukostasis

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