Chronic Myeloid Leukaemia

Overview – Chronic Myeloid Leukaemia

Chronic Myeloid Leukaemia (CML) is a myeloproliferative neoplasm characterised by uncontrolled proliferation of myeloid cells, commonly associated with the Philadelphia chromosome. While often asymptomatic in the early chronic phase, CML can evolve into a blast crisis resembling acute leukaemia. Early detection and targeted therapy have significantly improved survival.

Definition

• A clonal haematopoietic stem cell disorder marked by:
  • Uncontrolled myeloid proliferation
  • Presence of the Philadelphia chromosome (t(9;22)) in >80% of cases
• Characterised by three progressive phases

Aetiology

• Philadelphia chromosome:
  • Translocation t(9;22)(q34;q11)
  • Produces BCR-ABL fusion gene
  • Results in constitutive tyrosine kinase activity → cell proliferation

Pathophysiology

• Unregulated proliferation of myeloid precursors in bone marrow and blood
• Accumulation of immature granulocytes:
  • Neutrophils
  • Basophils
  • Eosinophils
• Bone marrow becomes hypercellular → eventual bone marrow failure
• Urate production increases due to cell turnover → risk of gout

Phases of CML

1. Chronic Phase

• May last several years
• Often asymptomatic or with mild symptoms
• Detected on routine blood tests

2. Accelerated Phase

• Disease progression
• ↑ Splenomegaly
• Fever, weight loss, increasing anaemia
• Warns of impending blast crisis

3. Blast Crisis

• Transforms into an acute leukaemia
• Rapid progression, very poor prognosis
• Features:
  • Sepsis, bleeding
  • Requires urgent bone marrow transplant

Clinical Features

• Demographics: Middle-aged adults (40–60 years)
• Symptoms:
  • Often asymptomatic initially
  • General malaise, fatigue, weight loss, fever
  • Anaemia symptoms: dyspnoea, pallor
  • Abdominal discomfort (from splenomegaly)
  • Gout (due to hyperuricaemia)
• Signs:
  • Splenomegaly (>75%)
  • Bruising (from thrombocytopenia)
  • Anaemia

Investigations

• FBC + Blood Film:
  • Marked leukocytosis with all stages of myeloid lineage
  • Anaemia
  • Variable platelet count
• Bone Marrow Biopsy:
  • Hypercellularity
  • Increased myeloid:erythroid ratio
• Cytogenetics:
  • Philadelphia chromosome (BCR-ABL)
  • Confirmed via FISH or PCR testing

Management

• Chronic Phase:
  • Imatinib (Glivec) – a tyrosine kinase inhibitor targeting BCR-ABL
  • Excellent prognosis with compliance
• Blast Crisis:
  • Behaves like acute leukaemia
  • Requires urgent bone marrow (stem cell) transplant
• Supportive:
  • Allopurinol or rasburicase for hyperuricaemia
  • Transfusions as needed

Summary – Chronic Myeloid Leukaemia

Chronic Myeloid Leukaemia (CML) is a BCR-ABL-driven myeloproliferative disorder often detected in its chronic phase. It progresses through an accelerated phase to a potentially fatal blast crisis if untreated. Early diagnosis and treatment with tyrosine kinase inhibitors like imatinib dramatically improve survival. For more on blood disorders, visit our Blood & Haematology Overview page.