Chronic Lymphocytic Leukaemia Flashcards
What is chronic lymphocytic leukaemia?
A monoclonal expansion of B-lymphocytes with accumulation of abnormal lymphocytes
Where do abnormal lymphocytes accumulate in chronic lymphocytic leukaemia?
- Blood
- Bone marrow
- Spleen
- Lymph nodes
- Liver
How do the lymphocytes in CLL appear morphologically?
Normal
What is abnormal about the lymphocytes in CLL?
They are immature and non-reactive
What is the result of the lymphocytes being immature and non-reactive in CLL?
Results in immunological compromise
How common is CLL compared to other leukaemias?
It represents about 1/4 of all leukaemias seen in clinical practice
When does CLL present?
It is largely a disease of older people
What causes CLL?
Unknown
What are the known risk factors for CLL?
- Age
- Radiation exposure
Are people in the UK exposed to radiation levels high enough to increase the risk of CLL?
No, it occurs after nuclear accidents etc
Describe the presentation of CLL?
Variable, with insidious onset
Are most people symptomatic at presentation of CLL?
No
How are people diagnosed with CLL asymptomatically?
Following routine blood tests
What are the symptoms of CLL?
- Susceptibility to infection
- Symmetrically enlarged lymph nodes
- Abdominal discomfort from an enlarged spleen
- Bleeding or petechiae in skin or mucous membranes
What are the signs of CLL?
- Localised or generalised lymphadenopathy
- Splenomegaly
- Hepatomegaly
- Petechiae
- Pallor
- Skin infiltration
- Tonsillar enlargement
What are the differential diagnoses for CLL?
- Other forms of leukaemia
- Lymphoma
- Myelodysplasia and myeloproliferative diseases
What investigations should be done in CLL?
- Blood tests
- Lymph node biopsy
- Other tests
What blood tests should be done in CLL?
- FBC
- Peripheral blood smear
- Direct anti-globulin test
- Bone marrow aspirate
What is found on FBC in CLL?
- Minimal clonal B cell lymphocytosis
- Normochromic, normocytic anaemia in advanced diseaes
What is found on peripheral blood smear in CLL?
Lymphocytosis, often with smudge cells
Why is a direct anti globulin test required in CLL?
Required before treatment to identify autoimmune-related haemolytic anaemias
What is found on bone marrow aspirate in CLL?
Lymphocytic replacement of normal marrow elements
When is a lymph node biopsy required in CLL?
If lymph nodes enlarge rapidly
Why is a lymph node biopsy required in CLL if lymph nodes enlarge rapidly?
To assess the possibility of transformation to a high-grade lymphoma
What is Richter’s syndrome?
The transformation of CLL into a high grade-lymphoma with enlarged lymph nodes, fever, weight loss, and pain
What other tests may be done in CLL?
- Immunophenotyping
- Measurement of immunoglobulin levels if repeated infection
- Testing for TP53 gene deletion before treatment
- Status of relevant infections
What infections should you check for in CLL?
- Hep B and C
- Cytomegalovirus
When should you check for hep B and C and cytomegalovirus in CLL?
Before chemo-immunotherapy or stem cell transplantation
What staging system is used for CLL in Europe?
Binet system
What is stage A CLL?
- Hb at least 10g/L
- Platelets at least 100x109/L
- Fewer than 3 lymph nodes areas are involved
What is stage B CLL?
- Hb and platelets levels as in stage A
- Three or more lymph nodes areas involved
What is stage C CLL?
Hb <10g/dL, platelets <100x109/L, or both
What is the curative treatment for CLL?
Apart from possibly stem cell transplants, there is no curative treatment for CLL
What is the role of chemotherapy in CLL?
Current standard chemotherapy regimes have been shown to prolong survival
When should chemotherapy be given in CLL?
Only to patients with active, symptomatic disease
What are the indications for chemotherapy in CLL?
- Weight loss >10%
- Extreme fatigue
- Fever related to leukaemia
- Night sweats
- Progressive marrow failure
- Autoimmune anaemia or thrombocytopenia not responding to prednisolone
- Progressive splenomegaly
- Massive lymphadenopathy
- Progressive lymphocytosis
What is the role of molecular markers in CLL?
Molecular markers now make it possible to identify patients more likely to have rapid progression of CLL, or be more resistant to standard treatment
What chemotherapy agents are currently used in CLL?
- Alkylating agents
- Purine analogues
- Monoclonal antibodies
- Steroids
What might steroids be used for in CLL?
- Treat autoimmune conditions
- Improve bone marrow function prior to chemotherapy when there is significant bone marrow infiltration
- Treat CLL that has not responded well to standard chemotherapies
What is the only known curative therapy for CLL?
Allogenic stem cell transplantation
What is the limitation of allogenic stem cell transplantation in CLL?
Majority of CLL patients are elderly, and the increased morbidity and mortality of such an intensive approach mean it is rarely justified
When might allogenic stem cell transplantation be a useful approach in CLL?
In younger patients
What treatment is required when there is splenomegaly and pancytopenia in CLL?
Splenectomy
What is the role of radiotherapy in CLL?
May be used palliatively, either for splenic irradiation or external beam radiotherapy for bulky nodal masses
When should treatment for CLL relapse be started?
Only in symptomatic patients
When can first-line therapy be repeated to treat relapse of CLL?
- If relapse or progression occurs at least 24-36 months after chemo-immunotherapy
- If TP53 deletion/mutation was excluded
How much does the median survival of CLL vary?
From 18 months to >10 years. depending on the stage
Describe the usual course of CLL?
Initial course that is relatively benign, followed by a terminal progressive and resistant phase lasting a year or two, followed by late phase
What causes morbidity in late phase CLL?
Disease and complications of treatment
What are older patients likely to die of with CLL?
Other causes, including second primary malignancies
