Chronic Myeloid Leukaemia

Question 1

What is CML?

Answer 1

Myeloid cell proliferation

Unlike acute it tends to be mature cell proliferation, with a predominance of granulocytes (neutrophils, basophils, eosinophils)

Question 2

What is it commonly associated with?

Answer 2

Philadelphia chromosome

T(9:22) translocation forming BCR-ABL1 gene, which causes abnormal tyrosine kinase production

This causes cells to be produced excessively

Question 3

Pathophysiology of CML

Answer 3

Triphasic
Chronic phase- may last up to 5 years completely asymptomatic, high white cells often provides incidental diagnosis

Accelerated phase- 10-20% proportion of abnormal blast cells, MAY develop Pancytopenia

Blast phase- 30% + proportion of abnormal blast cells, severe symptoms, usually fatal

Question 4

How does CML present?

Answer 4

Severity develops with phase progression

Hepatosplenomegaly- usually severe
Hyper metabolism
Gout due to high cell turnover -> high urate

Hyperleukocytosis related symptoms- eg headache, dizziness, blurred vision, confusion
Priapism

Question 5

How is CML investigated?

Answer 5

FBC will show high WBC, platelets may be normal or high, Hb may be normal or low
Blood film shows neutrophilia and myeloid precursors

Low LAP- leukocyte alkaline phosphate

Bone marrow biopsy not common but it would show high cellularity and high granulocytes

FISH for genetic abnormality (Philadelphia)

Question 6

Management for CML

Answer 6

Stem cell/bone marrow transplant in chronic phase can be curative

TK inhibitors eg imatinib, inhibit BCR-ABL protein action

Question 7

Who gets CML?

Answer 7

Usually presents in middle aged patients