Overview

Also known as chronic myelogenous leukaemia, chronic myeloid leukaemia (CML) is a cancer of the white blood cells characterised by uncontrolled proliferation of myeloid cells in the bone marrow and accumulation in the blood.

It is associated with a chromosomal translocation between the long arm of chromosome 9 and chromosome 22 called the Philadelphia chromosome – t(9;22)(q34;q11). This leads to the fusion of the ABL proto-oncogene from chromosome 9 and the BCR gene from chromosome 22. This leads to a protein that has increased tyrosine kinase activity.

People with CML may have the disease transform into an accelerated or blast phase where CML becomes acute myeloid leukaemia (AML) or acute lymphoblastic leukaemia (ALL). 

Epidemiology

  • Most common in people >65 years
  • The median age at diagnosis is 72 years

Risk Factors

  • Age >65 years
  • Exposure to mutagenic agents e.g. ionising radiation

Example History

A 75-year-old man feels generally unwell and fatigued for the last 3 months. He has had accompanying unexplained weight loss and abdominal discomfort. On examination, he has pallor and massive splenomegaly.

Investigations:

Haemoglobin:125 g/L(130 – 180 g/L)
Platelets:480 x 109/L(150 – 450 x 109/L)
Mean cell volume (MCV):80.0 fL(76.0 – 98.0 fL)
White blood cells (WBC):21.0 x 109/L(3.0 – 10.0 x 109/L)
Neutrophils:16.5 x 109/L(2.00 – 7.00 x 109/L)
Lymphocytes:1.30 x 109/L(1.00 – 4.00 x 109/L)
Monocytes:1.30 x 109/L(0.20 – 0.80 x 109/L)
Eosinophils:0.74 x 109/L(0.00 – 0.40 x 109/L)
Blood film:Band cells seen

Presentation

Patients are usually diagnosed in the chronic phase. They are usually older and may have the following features:

  • May be picked up incidentally in an asymptomatic patient
  • Features of anaemia:
  • Marked splenomegaly is a common feature:
    • Due to the increased sequestration of cells
    • This can be large enough to cause abdominal discomfort
  • Constitutional symptoms – unexplained weight loss, night sweats, fever, excess sweating
  • Bruising – if thrombocytopenia develops due to bone marrow crowding

Differential Diagnoses

Acute myeloid leukaemia (AML)

  • Blood film shows blast cells, whereas, in CML, there are cells at different stages of maturation
  • Blood film shows Auer rods

Chronic lymphocytic leukaemia (CLL)

  • In CLL patients are usually asymptomatic, but in CML they may have anaemia, weight loss, and night sweats
  • In CLL, a full blood count shows leukocytosis and increased lymphocytes. In CML, the lymphocyte numbers are usually normal
  • In CLL blood films show smudge/smear cells

Investigations

All patients

  • Full blood count (FBC) and white cell differential:
    • Haemoglobin: may be low/normal
    • White cell count: increased
    • Platelets: may be increased
  • Blood film:
    • Shows myeloid cells in different stages of maturation – they are all mature or maturing
    • May show band cells, metamyelocytes, myelocytes, promyelocytes, basophilia, eosinophilia etc.
  • Urea and electrolytes (U&Es):
  • Lactate dehydrogenase (LDH):
    • May be increased due to cell turnover
  • Bone marrow biopsy – confirms disease and used for karyotyping:
    • Shows myeloid hyperplasia
  • Cytogenetic analysis:
    • Shows the BCR-ABL fusion and may show the Philadelphia chromosome

Management

All patients

Management is carried out by a haematology/oncology consultant.

  • 1st-line: tyrosine kinase inhibitor e.g. imatinib
  • Other options are stem cell transplants

Complications

  • Pancytopenia – suggests blast crisis
    • Sudden worsening and progression of CML, giving rise to symptoms similar to that of an acute leukaemia
  • Increased susceptibility to infection
  • More severe infection

Prognosis

  • The prognosis has improved since tyrosine kinase inhibitors have been introduced. Those diagnosed with CML in the chronic phase have a near-normal life expectancy.

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