Chronic Myeloid Leukaemia

Question 1

What is CML?

Answer 1

Malignant clonal disease characterised by uncontrolled proliferation of myeloid cells in BM + blood, distinguished from AML by its slower progression
Myeloproliferative disorder: increase in production of end cells

Question 2

Describe the aetiology of CML

Answer 2

Malignant proliferation of stem cells
95% of cases have a chromosomal translocation between chromosomes 9 + 22 to form the Philadelphia chromosome (fusion gene BCR/ABL)

Question 3

What are 3 variants of CML?

Answer 3

Ph-negative CML: worse prognosis
Chronic neutrophilic leukaemia
Eosinophilic leukaemia

Question 4

Describe the pathogenesis of CML

Answer 4

Philadelphia chr results in the formation of the BCR-ABL fusion gene
The product of this gene enhances tyrosine kinase activity + drives cell replication
Still get features of BM suppression due to crowding out of other cells

Question 5

List the 3 phases of CML

Answer 5

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

Question 6

Describe the epidemiology of CML

Answer 6

Incidence increases with age
Mean age 40-60 yrs
M > F

Question 7

List 3 risk factors for CML

Answer 7

ionising radiation
Benzene
IBD

Question 8

How do many cases of CML present?

Answer 8

ASYMPTOMATIC in 40-50% of cases: diagnosed on routine blood count
May present during a blast crisis with symptoms of AML + ALL

Question 9

List 3 symptoms of hypermetabolism in CML

Answer 9

Weight loss
Malaise
Sweating

Question 10

List 5 symptoms of bone marrow failure in CML

Answer 10

Lethargy  
Dyspnoea 
Easy bruising  
Epistaxis  
Abdominal discomfort + early satiety: due to splenic enlargement

Question 11

List 4 rarer symptoms of CML

Answer 11

Gout
Hyperviscosity symptoms (visual disturbance, headaches, priapism)
Athralgia
Sternal tenderness

Question 12

Give 2 signs of CML

Answer 12

SPLENOMEGALY: most common physical finding (90% of cases) Not really seen in AML as doesn’t have time to form
Hepatomegaly

Question 13

Give 3 signs of bone marrow failure in CML

Answer 13

Pallor
Bleeding
Ecchymosis

Question 14

Describe the bloods taken in CML?

Answer 14

High WCC with whole spectrum of myeloid cells: high neutrophils, myelocytes, basophils, eosinophils 
Low Hb  
Deranged platelets
High uric acid  
High B12 + transcobalamin I  
Low neutrophil ALP score

Question 15

How does platelet count vary through phases of CML?

Answer 15

HIGH: Chronic or accelerated phase)

NORMAL/ LOW: accelerated or blast phase

Question 16

What is seen on blood film in CML?

Answer 16

Immature granulocytes

Question 17

What is seen on bone marrow aspirate or biopsy in CML

Answer 17

Hypercellular with raised myeloid-erythroid ratio

Question 18

What is seen on cytogenetics in CML?

Answer 18

Philadelphia chromosome