Leukaemia (chronic myeloid)

Question 1

Definition

Answer 1

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

Aetiology

Answer 2

· Malignant proliferation of stem cells

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

Question 3

Variants

Answer 3

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

Question 4

Pathogenesis

Answer 4

o The Philadelphia chromosome results in the formation of the BCR-ABL fusion gene

o The product of this gene enhances tyrosine kinase activity and drives cell replication

Question 5

Three phases

Answer 5

o Relatively stable chronic phase (4-6 yr duration)

o Accelerated phase (3-9 months)

o Acute leukaemia phase - blast transformation

Question 6

Epidemiology

Answer 6

· Incidence increases with age

· Mean age of diagnosis: 40-60 yrs

· 4 x more common in MALES

Question 7

Presenting symptoms (hypermetabolic)

Answer 7

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

· Hypermetabolic Symptoms:
o Weight loss
o Malaise
o Sweating

Question 8

Presenting symptoms (bone marrow failure)

Answer 8

o Lethargy
o Dyspnoea
o Easy bruising
o Epistaxis
o Abdominal discomfort and early satiety

o Rare symptoms:
· Gout
· Hyperviscosity symptoms (visual disturbance, headaches, priapism)

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

Question 9

Signs on physical examination

Answer 9

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

· Signs of bone marrow failure:
o Pallor
o Bleeding
o Ecchymosis

Question 10

Investigations (blood)

Answer 10

· Bloods

o FBC
· High WCC - very high - any result above 30 is likely to be CML
· Low Hb
· High basophils/neutrophils/eosinophils
· High/normal/low platelets
· High uric acid
· High B12 and transcobalamin I

· Blood Film
o Immature granulocytes

Question 11

Investigations (other)

Answer 11

· Bone Marrow Aspirate or Biopsy
o Hypercellular with raised myeloid-erythroid ratio

· Cytogenetics
o Show the Philadelphia chromosome