Chronic Myeloid Leukaemia

Question 1

what is the definition of CML?

Answer 1

Uncontrolled clonal proliferation of myeloid cells

Question 2

what is the epidemiology of CML?

Answer 2

Adult disease, 40-60 yrs
Slight male predominance
Rare in childhood

Question 3

what is the aetiology of CML?

Answer 3

More than 80% have the Philadelphia chromosome which forms a fusion gene BCR/ABL on chromosome 22, which has tyrosine kinase activity - stimulates cell division

Question 4

what are the risk factors for CML?

Answer 4

Radiation exposure

Age

Question 5

what is the pathophysiology of CML?

Answer 5

Increased proliferation of the granulocytic cell line without the loss of their capacity to differentiate. Consequently, the peripheral blood cell profile shows an increased number of granulocytes and their immature precursors, including occasional blast cells

Question 6

what are the key presentations of CML?

Answer 6

Symptomatic anaemia, abdominal discomfort

Question 7

what are the signs of CML?

Answer 7

On examinations palpable spleen below the costal margin
Pallor
gout

Question 8

what are the symptoms of CML?

Answer 8

tiredness/lethargy weight loss night sweats
Fever
Bleeding
Shortness of breath

Question 9

what are the first line investigations for CML?

Answer 9

FBC - White blood cells count high, with the whole spectrum of myeloid cells i.e. increased; neutrophils, myelocytes, basophils and eosinophils. Low Hb (normocytic), platelets low

Question 10

what are the gold standard investigations for CML?

Answer 10

Bone marrow biopsy - cytogenetics, show lots of white cells at all stages of maturity, hypercellular
Karyotyping - abnormality on 9 and 22 chromosome

Question 11

what are the differential diagnoses for CML?

Answer 11

other myeloproliferative neoplasms

Question 12

how is CML managed?

Answer 12

Baseline quantitative PCR for BCR::ABL1
Start Imatinib 400mg daily
Stem cells transplant

Question 13

how is CML monitored?

Answer 13

Monitor BCR::ABL1 every 3 months
Monitor FBC for hematologic remission
Reassess spleen size at 3 months

Question 14

what are the complications of CML?

Answer 14

Hepatomegaly and/or splenomegaly.
Worsening anemia.
Changes in platelet count changes resulting in clotting or bleeding complications.
Recurrent infections.
Bone pain.
Fever.

Question 15

what is the prognosis of CML?

Answer 15

With treatment - normal life expectancy, research suggests drug can be stopped after 5 years with good response