Chronic leukaemia

Question 1

Which cells can be affected in chronic leukaemia

Answer 1

• Myeloid: neutrophils eosinophils and basophils

* Lymphoid: B lymphocytes

Question 2

What are the presenting features of chronic leukaemia

Answer 2

• none
• Lethargy, night sweats, weight loss
• Symptoms of anaemia
• Lymphadenopathy
• Infection

Question 3

Describe the diagnosis of chronic leukaemia

Answer 3

• Flow cytometry: clonal population of B lymphocytes - CD5, 19,20,23, weak surface Ig
• CLL has a unique immunophenotype (co expression of CD5, 19 and 23)
• Often the diagnosis is incidental i.e. FBC - lymphocytosis

Question 4

Explain the clinical staging of chronic leukaemia

Answer 4

Binet
•Stage A: <3 involved nodes - 10 year survival
•Stage B >3 involved nodes liver, spleen - 7 year survival
•Stage C: anaemia or thrombocytopenia - 2 years

Question 5

Explain the cryogenics of chronic leukaemia

Answer 5

• Traditional G banding cytogenetics on metaphase cells not useful in CLL
• Interphase FISH
• Probe chromosome 17p and 12

Question 6

17 p deletions

Answer 6

• Aggressive disease
• Delp 17p results in loss of p53
• Refractory to chemo as it doesn’t work as well if you have lost the tumour suppressor gene
• Patients may respond to steroids and antibodies

Question 7

Describe B chronic lymphoid leukaemia

Answer 7

• Complex disease with variable behaviour

* therapy is tailored to the circumstances i.e. p53 deletion or 11q22 mutation

Question 8

What are the immune complications of chronic lymphoid leukaemia?

Answer 8

• Autoimmune haemolytic anaemia - 5-10%

* Autoimmune thrombocytopenia - <5%

Question 9

How do you manage the immune complications of CLL?

Answer 9

• Treat with steroids

* Treat CLL

Question 10

What is the appearance of a blood film in a patient with autoimmune haemolytic anaemia?

Answer 10

•Spherocytes

Question 11

Why are patients with CLL more prone to infection?

Answer 11

• Hypogammaglobulinaemia
• Cell mediated immunity is impaired
• T cell lymphopenia
• Neutropenia
• Defects complement activation

Question 12

What are the effects of CLL treatment?

Answer 12

• Sweats, weight loss, symptomatic nodes

* Bone marrow failure: anaemia, thrombocytopenia

Question 13

What is the appearance of chronic phase CML?

Answer 13

• Variety of myeloid cells

* Varying maturity

Question 14

What is the clinical presentation of chronic myeloid leukaemia?

Answer 14

• May be asymptomatic
• Fatigue
• Weight loss
• Night sweats
• Abdominal discomfort (because of splenomegaly)
• Splenomegaly

Question 15

What are the phases of CML?

Answer 15

• Chronic phase
• Accelerated phase
• Myeloid blast phase

Question 16

Describe the genetics of CML

Answer 16

• BCR - ABL gene fusion encodes oncoprotein

* Upregulates proliferation in the marrow

Question 17

Describe the diagnosis of CML

Answer 17

• Blood film and clinical features
• Molecular test on blood (BCR-ABL, PCR/FISH)
• Cytogenetic analysis (karyotype)
• If they are BCR-ABL negative it is not CML

Question 18

What is the treatment of CML?

Answer 18

Imatinib - tyrosine kinase inhibitor

Question 19

What are the complications of CML?

Answer 19

• Imatinib resistance or intolerance
• need for 2nd or 3rd line tyrosine kinase inhibitors
• Accelerated phase or blasé crisis