Chronic Myeloid Leukaemia

Question 1

Define Chronic Myeloid Leukaemia (CML)?

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

What is the aetiology of CML?

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

What are some of the variants of CML?

Answer 3

Ph-negative CML
Chronic Neutrophilic Leukaemia
Eosinophilic Leukaemia

Question 4

What is the pathogenesis of CML?

Answer 4

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

Question 5

What are the three stages of CML?

Answer 5

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

Question 6

What is the epidemiology of CML?

Answer 6

Incidence increases with age
Mean age of diagnosis: 40-60 yrs
4x more common in MALES

Question 7

What are the presenting symptoms of CML?

Answer 7

Asymptomatic in 40-50% of cases - diagnosed in routine blood count
Hypermetabolic Symptoms
Bone Marrow Failure Symptoms

Question 8

What are the Hypermetabolic Symptoms in CML?

Answer 8

Weight Loss
Malaise
Sweating

Question 9

What are the Bone Marrow Failure symptoms in CML?

Answer 9

Lethargy
Dyspnoea 
Easy bruising 
Epistaxis 
Abdominal discomfort and early satiety

Question 10

What are the rare symptoms of CML?

Answer 10

Gout 
Hyperviscosity symptoms (visual disturbance, headaches, pripaism)

Question 11

What might happen in an blast crisis with CML?

Answer 11

May present with symptoms of AML and ALL

Question 12

What are the signs of CML on physical examination?

Answer 12

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

Signs of Bone Marrow Failure (Pallor, Bleeding, Ecchymosis)

Question 13

What bloods would you do for CML and what would you see?

Answer 13

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

Question 14

What would you see on a blood film for CML?

Answer 14

Immature granulocytes

Question 15

What would you see in a Bone Marrow Aspirate or Biopsy for CML?

Answer 15

Hypercellular with raised myeloid-erythoid ratio

Question 16

What would you see if you did cytogenetics for CML?

Answer 16

Show the philadelphia chromosome