Chronic Lymphoblastic Leukaemia

Question 1

What is chronic lymphoblastic leukaemia?

Answer 1

https://www.youtube.com/watch?v=Wn3fylOqUZU

Results from the clonal expansion of small lymphocytes and is almost invariably (95%) B cell in origin.

Accumulation of mature B cells that have escaped programmed cell death and undergone cell cycle arrest in the G0/G1 phase is the hallmark of CLL.

Commonest leukaemia in adults

Deletion of chromosome 13

Question 2

What is the difference in cell behaviour between CML and CLL?

Answer 2

• CML - cells divide to quickly
• CLL - cells don’t die when they should

Question 3

Which sex is CLL more common in?

Answer 3

Males

Question 4

What can be a trigger for the development of CLL?

Answer 4

Pneumonia

Question 5

What are symptoms of CLL?

Answer 5

Mainly asymptomatic

Common findings:

• Bone marrow failure
  
  • Symptoms of Anaemia
  • Recurrent infection
• Painless lumps
• Left upper quadrant discomfort (splenomegaly)
• Fever and sweats

Less common findings:

• Heparomegaly
• Infections (hypogammaglobulinaemia),
• Weight loss

Question 6

Why might someone with CLL get recurrent infections?

Answer 6

Due to functional leucopenia and immune failure (reduced immunoglobulins)

Question 7

What can cause anaemia in CLL?

Answer 7

• Autoimmune haemolytic anaemia (warm)
• Marrow infiltration

Question 8

Why might someone with CLL have upper left quadrant discomfort?

Answer 8

Splenomegaly

Question 9

What signs might someone with CLL have?

Answer 9

• Anaemia
• Fever
• Lymphadenopathy - may be single area or generalised
• Hepatosplenomegaly - sometimes massive

Question 10

What is the characteristic feature of lymphadenopathy seen in CLL?

Answer 10

Enlarged, rubbery, non-tender nodes

Question 11

What investigations might you do for someone with suspected CLL?

Answer 11

• Blood count
• Blood film
• Bone marrow.
• Immunophenotyping
• Direct Coombs’ test
• Immunoglobulins

Question 12

What might you see on Blood count in someone with CLL?

Answer 12

• Hb - normal or low
• WBC - raised and may be very high; with lymphocytosis
• Platelets - normal or low.

Question 13

What might you see on blood film in someone with CLL?

Answer 13

• Small/medium sized mature and normal appearing lymphocytes
• Smudge cells
• No immature blasts
• Haemolysis

Question 14

Why would you do direct coombs test in someone with CLL?

Answer 14

To check for autoimmune haemolysis

Question 15

What might you find when investigating serum immunoglobulins?

Answer 15

Hypogammaglobulinaemia - prone to infection

Question 16

What might you find in the bone marrow of someone with CLL?

Answer 16

Reflects peripheral blood, often very heavily infiltrated with lymphocytes.

Question 17

What might you find when immunophenotyping someone for CLL?

Answer 17

CD19+, CD5+, CD23+ B cells with weak expression of CD20, CD79b and surface immunoglobulin

Question 18

Diagnosis of CLL

Answer 18

• Blood >5 x10 ^9lymphocytes
• Bone marrow >30% lymphocutes (marrow infiltration)
• Characterostoc immunotyping

Question 19

What are complications of CLL?

Answer 19

• Autoimmune haemolysis
• Increased risk of infection due to hypogammaglobulinaemia
• Marrow failure

Question 20

What are individuals most likely to die of in CLL?

Answer 20

Infection

Question 21

What organism most commonly cause death in those with CLL?

Answer 21

• Pneumococcus
• Meningococcus
• Haemophilus
• Candidiasis
• Aspergillosis

Question 22

What are indications for treatment in CLL?

Answer 22

• Progressive bone marrow failure
• Massive lymphadenopathy
• Progressive splenomegaly (pain, discomfort)
• Lymphocyte doubling time <6 months or >50% increase over 2 months
• Systemic symptoms
• Autoimmune cytopenias

Question 23

How would you manage someone with CLL?

Answer 23

• Often none/supportive care/IV immunoglobulins
• Cytotoxic chemotherapy
• Monoclonal antibodies
• Corticosteroids
• Radiotherapy
• Novel agents (switch off bits of the B cell receptor pathway to stop the stimulation)
  
  • Bruton tyrosine kinase inhibitor
  • PI3K inhibitor
  • BCL-2 inhibitor

Question 24

What cytotoxic chemotherapies are used in treating CLL?

Answer 24

• Fludarabine
• Bendamustine

Question 25

What monoclonal antibodies are used in treating CLL?

Answer 25

• Rituximab
• Obinutuzamab
• Alemtuzumab
• Ofatumumab

Question 26

Why might steroids be used in management of CLL?

Answer 26

Managing autoimmune haemolysis

Question 27

What is radiotherapy used for in treating CLL?

Answer 27

Helps lymphadenopathy and splenomegaly

Question 28

What is the prognosis for CLL?

Answer 28

• 1/3 never progress
• 1/3 progress slowly
• 1/3 progress actively

Question 29

What are poor prognostic markers in CLL?

Answer 29

• Advanced disease (Binet stage B or C)
• Atypical lymphocyte morphology
• Rapid lymphocyte doubling time (<12 mth)
• CD 38+ expression
• Loss/mutation p53; del 11q23 (ATM gene)
• Unmutated IgVH gene status
• Male

Question 30

What is the first line treatment for CLL?

Answer 30

Chlorbumacil combined with prednisone - associated with 60-90% intital response rate and a complete response in up to 20% of all patients.

Question 31

What is the characteristic cell type seen on blood film in CLL?

Answer 31

Smudge cells

Question 32

What’s richter transformation?

Answer 32

Ritcher’s transformation occurs when leukaemia cells enter the lymph node and change into a high-grade, fast-growing non-Hodgkin’s lymphoma. Patients often become unwell very suddenly.

Ritcher’s transformation is indicated by one of the following symptoms:

• lymph node swelling
• fever without infection
• weight loss
• night sweats
• nausea
• abdominal pain