Chronic Lymphoblastic Leukaemia Flashcards
What is chronic lymphoblastic leukaemia?
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
What is the difference in cell behaviour between CML and CLL?
- CML - cells divide to quickly
- CLL - cells don’t die when they should
Which sex is CLL more common in?
Males
What can be a trigger for the development of CLL?
Pneumonia
What are symptoms of CLL?
Mainly asymptomatic
- Recurrent infection
- Symptoms of Anaemia
- Painless lumps
- Left upper quadrant discomfort
- Weight loss
Why might someone with CLL get recurrent infections?
Due to functional leucopenia and immune failure (reduced immunoglobulins)
What can cause anaemia in CLL?
- Autoimmune haemolytic anaemia
- Marrow infiltration
Why might someone with CLL have upper left quadrant discomfort?
Splenomegaly
What signs might someone with CLL have?
- Anaemia
- Fever
- Lymphadenopathy - may be single area or generalised
- Hepatosplenomegaly - sometimes massive
What is the characteristic feature of lymphadenopathy seen in CLL?
Enlarged, rubbery, non-tender nodes
What investigations might you do for someone with suspected CLL?
- Blood count
- Blood film
- Bone marrow.
- Immunophenotyping
- Direct Coombs’ test
- Immunoglobulins
What might you see on Blood count in someone with CLL?
- Hb - normal or low
- WBC - raised and may be very high; with lymphocytosis
- Platelets - normal or low.
What might you see on blood film in someone with CLL?
- Small/medium sized mature and normal appearing lymphocytes
- Smudge cells
- No immature blasts
- Haemolysis
Why would you do direct coombs test in someone with CLL?
To check for autoimmune haemolysis
What might you find when investigating serum immunoglobulins?
Hypogammaglobulinaemia - prone to infection
What might you find in the bone marrow of someone with CLL?
Reflects peripheral blood, often very heavily infiltrated with lymphocytes.
What might you find when immunophenotyping someone for CLL?
CD19+, CD5+, CD23+ B cells with weak expression of CD20, CD79b and surface immunoglobulin
What are complications of CLL?
- Autoimmune haemolysis
- Increased risk of infection due to hypogammaglobulinaemia
- Marrow failure
What are individuals most likely to die of in CLL?
Infection
What organism most commonly cause death in those with CLL?
- Pneumococcus
- Meningococcus
- Haemophilus
- Candidiasis
- Aspergillosis
What are indications for treatment in CLL?
- Progressive bone marrow failure
- Massive lymphadenopathy
- Progressive splenomegaly
- Lymphocyte doubling time <6 months or >50% increase over 2 months
- Systemic symptoms
- Autoimmune cytopenias
How would you manage someone with CLL?
- None/supportive care/IV immunoglobulins
- Cytotoxic chemotherapy
- Monoclonal antibodies
- Corticosteroids
- Radiotherapy
- Novel agents
- Bruton tyrosine kinase inhibitor
- PI3K inhibitor
- BCL-2 inhibitor
What cytotoxic chemotherapies are used in treating CLL?
- Fludarabine
- Bendamustine
What monoclonal antibodies are used in treating CLL?
- Rituximab
- Obinutuzamab
- Alemtuzumab
- Ofatumumab
Why might steroids be used in management of CLL?
Managing autoimmune haemolysis
What is radiotherapy used for in treating CLL?
Helps lymphadenopathy and splenomegaly
What is the prognosis for CLL?
- 1/3 never progress
- 1/3 progress slowly
- 1/3 progress actively
What are poor prognostic markers in CLL?
- 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
What is the first line treatment for CLL?
Chlorbumacil combined with prednisone - associated with 60-90% intital response rate and a complete response in up to 20% of all patients.
What is the characteristic cell type seen on blood film in CLL?
Smudge cells
