Acute Leukaemia

Background and Epidemiology

• Both are bone marrow malignancies
  • Acute myeloid leukaemia is when cells of myeloid lineage proliferate and replace normal haematopoietic cells.  Acute lymohocytic leukaemia is this but with lymphoid cells
• ALL is the most common cancer in children (75% of cases are in children <6 years and the incidence is 3/100,000/year- representing 12% of all leukaemias but 80% in children)
  • Peak age 2-4 years old
• AML is more commonly seen in adults (average age of onset ~70 years old).  Occurs in 5-8/100,000.
• ALL in childhood has a relatively high cure and survival rate (80-95%).  In contrast, adult disease is very rarely cured and the prognosis is poor (20-40%)

Pathophysiology/Aetiology

• Most patients with acute leukaemia do not have an identifiable cause e.g.
  • ionising radiation (e.g. radiotherapy)
  • chemotherapy
  • hereditary genetic associations e.g. Down’s syndrome; Fanconi’s anaemia; Bloom’s syndrome; rarer family conditions (increased risk if sibling has acute leukaemia
  • Haematological disorder (AML>ALL) e.g. Chronic myeloid leukaemia; aplastic anaemia; myelodysplastic syndrome; polycythaemia vera; myelofibrosis; paroxysmal nocturnal haemoglobinuria
• In acute leukaemias, an early haematopoietic cell undergoes genetic changes which causes uncontrolled proliferation and lack of differentiation into mature cells
  • genetic changes include loss of function mutations of transcription factor genes (block differentiation) and those causing constitutively active protein kinases (enhanced proliferation)
• This causes a rapid build up of these cells and subsequent loss of mature cells (anaemia, thrombocytopenia and leukopenia) and depositing of abnormal cells in the bone marrow, liver and spleen (due, in part, to failure of apoptotic mechanisms)

Presentation

• Usually fairly acute (days-weeks) onset of symptoms which can rapidly deteriorate
• Common symptoms include
  • Fever is a common symptom
    • Assume secondary to infection until proven otherwise
  • Fatigue, dizziness, palpitation and dyspnoea all secondary to anaemia
  • Bone pain, gum pain, upper abdominal pain
• Patients may have a history of chronic/recurrent respiratory tract infections
• Signs may include
  • Pallor
  • SIRS/sepsis
    • Respiratory infection
    • Fever
  • Petechial rash (particularly on the lower extremities)
  • Lymphadenopathy, splenomegaly and hepatomegaly
• Rarely, patients can present with leukostasis (white cell count typically greater than 100,000/μl)
  • Confusion/altered conscious level and/or neurological deficits (essentially intracranial haemorrhage)
  • Respiratory distress (pulmonary haemorrhage)

Investigations

• FBC-
  • leukocytosis is typical but levels can be normal/low
  • normocytic anaemia
  • thrombocytopenia
  • blasts may be seen in the peripheral blood
• U&Es/LFTs
  • Often raised urate (increased haemolysis)
  • Signs of liver failure or kidney failure
• For the definitive diagnosis, bone marrow biopsy/aspiration is required
  • >20% blasts is diagnostic
  • Typing of the leukaemia e.g. AML vs ALL, is done by the lab usually by microscopy, and further subtype classification is also done
    • Auer rods are seen only in AML and are pathogenomic.  Cytoplasmic granules are also suggestive.  Neither found in ALL.  Flow cytometry can also help to differentiate.
    • Immunochemistry can further subtype ALL/AML
• Imaging may also be useful for evaluating severity of disease

Management

NB This is largely a post-graduate topic and understanding of specific regimens/treatments isn’t required.

• Combination chemotherapy is the mainstay of treatment
  • In ALL
    • Induction
    • Intensification
    • CNS prophylaxis
    • Maintenance typically lasting 2 years or more
  • In AML
    • Induction
    • Consolidation
• Bone marrow transplant can be used
• Stem cell transplantation is also an option

NB Patients may require acute treatment of complications e.g. antibiotics

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