Chronic Myeloid Leukaemia

Question 1

What is CML? Who deos it occur in?

Answer 1

Uncontrolled clonal proliferation of myeloid cells

40-60 years

Question 2

What is aetiology of CML?

Answer 2

Philadelphia chromocome
Hybrid chromosome with reciprocal translocation between the long arm of chromosme 0 and the long arm of chromosome 22 forming fusion gene BCR- ABL which has tyrosine kinase activity

Question 3

What are symptoms of CML?

Answer 3

Chronic and insidious
Weight loss
Tiredness
FEver
Sweats
Gout due to purine breakdown
Bleeding (platelet dysfunction)
Abdominal discomfort (splenic enlargement)

Question 4

Signs of CML?

Answer 4

Splenomegaly (often massive)
Hepatomegaly
Anaemia
Bruising

Question 5

What investigations in CML?

Answer 5

WCC raised
Myeloid cells:
Raised neutrophils, monocytes, basophils, eosinophils
Normal/low Hb
Platelets variable

Raised urate
Raised B12
Bone marrow hypercellular

Cytogenetic analysis of blood or bone marrow for philadelphia chromosome

Question 6

What is the natural history of CML?

Answer 6

Chronic lasting months or years with few symptoms
Accelerated phase with increasing symptoms, spleen size and difficulty in controlling counts
Blast transformation with features of acute leukaemia and death

Question 7

Mx of CML?

Answer 7

Imatinib - BCRABL tyrosine kinase inhibitor = 1st line
SE: nausea, cramps, rash, oedema

More potent 2nd generation inhibitors:
Dasatinib

Hydroxycarbamide

Allogenic bone marrow transplantaiton from HLA matched ibling or donor is the ony cure
Only rarely used 1st line in younger patients due to morbidiity/mortality risk