Leukaemia, Chronic Myeloid (CML)

Question 1

Define

Answer 1

DEFINITION: chronic myeloblastic leukaemia is a malignant clonal disease characterised by proliferation of granulocyte precursors in the bone marrow and blood, distinguished from AML by its slower progression

Question 2

Causes

Answer 2

Malignant proliferation of stem cells

95% of cases have a chromosomal translocation between chromosomes 9 and 22 to form the Philadelphia chromosome

Variants of CML include:

• Ph-negative CML
• Chronic neutrophilic leukaemia
• Eosinophilic leukaemia

Pathogenesis

• The Philadelphia chromosome results in the formation of the BCR-ABL fusion gene
• The product of this gene enhances tyrosine kinase activity and drives cell replication

THREE phases of CML

• Relatively stable chronic phase (4-6 yr duration)
• Accelerated phase (3-9 months)
• Acute leukaemia phase - blast transformation

Question 3

Epidemiology

Answer 3

Incidence increases with age

Mean age of diagnosis: 40-60 yrs

4 x more common in MALES

Question 4

Symptoms

Answer 4

ASYMPTOMATIC in 40-50% of cases - diagnosed on routine blood count

Hypermetabolic Symptoms:

• Weight loss
• Malaise
• Sweating

Bone Marrow Failure Symptoms:

• Lethargy
• Dyspnoea
• Easy bruising
• Epistaxis
• Abdominal discomfort and early satiety
• Rare symptoms:

Gout

Hyperviscosity symptoms (visual disturbance, headaches, priapism)

• May present during a blast crisis with symptoms of AML and ALL

Question 5

Signs

Answer 5

SPLENOMEGALY - most common physical finding (90% of cases)

Signs of bone marrow failure:

• Pallor
• Bleeding
• Ecchymosis

Question 6

Investigations

Answer 6

Bloods

FBC

• High WCC
• Low Hb
• High basophils/neutrophils/eosinophils
• High/normal/low platelets
• High uric acid
• High B12 and transcobalamin I

Blood Film

• Immature granulocytes

Bone Marrow Aspirate or Biopsy

• Hypercellular with raised myeloid-erythroid ratio

Cytogenetics

• Show the Philadelphia chromosome