Chronic leukaemia

Question 1

Describe the pathogenesis of chronic lymphoid leukaemia (CLL)

Answer 1

• Lymphocytes esp B cells are affected there is an acculuation of mature B cells which do not function correctly
• The B cells accumulate due to escaping programmed cell death and undergoing cell-cycle arrest in the Go/G1 phase (not due to rapid proliferation like in acute leukaemias)
• Eventually the build up of B cells/lymphocytes in the bone marrow spill out into the blood, they then esp like to spread to the lymph nodes (now also a lymphoma)
• Due to build up in the bone marrow they can cause a pancytopenia picture

Question 2

What is the commonest type of leukaemia ?

Answer 2

CLL

Question 3

What is the typical presentation of chronic lymphoid leukaemia ?

Answer 3

• Often nothing, presting as a surprise finding on a routine FBC e.g. done pre-op
• Patient may be anaemic or infection-prone resulting in investigations which find it
• If severe there may be decreased weight, night sweats

Question 4

What are some of the signs of CLL ?

Answer 4

• Enlarged, rubbery, non-tender nodes
• Splenomegaly and hepatomegaly may also be present

Question 5

What are the classic findings on test for CLL?

Answer 5

See increased lymphocytes

Later there may be evidence of autoimmune haemolysis and marrow infiltration ==> pancytopenia picture with anaemia, bleeding and infections

Question 6

What cells are often seen in association with CLL on blood smear ?

Answer 6

Many lymphocytes and may see ‘smear’ or ‘smudge’ cells which are fragile damage cells hence smudged appearance

Question 7

What is the treatment for CLL?

Answer 7

Fludarabine + cyclophosphamide + rituximab

Question 8

What is the main causative mutation of CML ?

Answer 8

• Philidelphia chromosome - due to a translocation between chromosome 9 and 22 - t(9:22)(q34; q11).
• This results in a BCR-ABL gene which codes for a fusion protein which has tyrosine kinase activity in excess of normal

Question 9

What age does CML usually present at ?

Answer 9

60-70

Question 10

What are the clinical features of CML?

Answer 10

• anaemia: lethargy
• weight loss and sweating are common
• splenomegaly may be marked → abdo discomfort
• an increase in granulocytes at different stages of maturation +/- thrombocytosis
• decreased leukocyte alkaline phosphatase
• may undergo blast transformation (AML in 80%, ALL in 20%)

Question 11

What is the 1st line treatment of CML?

Answer 11

Imatinib (inhibitor of the tyrosine kinase associated with the BCR-ABL defect)