Chronic lymphocytic leukaemia Flashcards
What is a leukaemia?
Blood cancer that arises due to failure of hematopoietic differentiation –> accumulation of immature or dysfunctional leucocytes
How does the peripheral blood of the a patient with acute leukaemia differ to that of a patient with chronic leukaemia?
In acute:
- hematopoiesis arrests early on resulting in immature leukocytes in bone marrow.
- they are too immature to leave bone marrow –> low peripheral blood cells
In chronic:
- high WCC
(majority of CLL have B cell malignancy)
What is CLL?
Commonest leukaemia worldwide
Clonal disorder of mature CD5+/CD19+ B cells
Wheres is the tumour found in CLL?
- Bone marrow
- Peripheral blood
- Secondary lymphoid tissues (spleen, lymph nodes)
What are the characteristic features of CLL
- infection
- autoimmunity
- bone marrow failure
What is the age distribution of patients with CLL?
- Greater incidence in those >60
- Although 20-30% of cases are diagnosed in patients under 55
Albeit the incidence of this is 2-5/10000
Up to 50% of patients are diagnosed following an incidental blood test finding.
In those who are symptomatic how would you expect them to present?
Symptoms
- repeat infections (pneumonia, Herpes)
- night sweats
- fever
- weight loss
- muscle wastage
- bruising
- abdominal pain (splenomegaly)
Signs
- enlarged lymph nodes
- splenomegaly
- anaemia
What causes CLL?
Idiopathic: is it infection? chemical exposure? AI? DM?
Genetic component
- 5% of cases are familial
- incidence doubles if a first degree relative with CLL or another lymphoproliferative disease
What is the scoring system predominantly used to diagnose CLL?
Matutes scoring system
- a flow cytometry system which measures surface immunoglobulins (cd5, cd23, cd79b (a component of B cell receptor) and antigen FMC7
(used to differentiate CLL from other B cell lymphoproliferative disease, not that great at differentiating from atypical/mixed CLL)
What is the role of doing a blood film in diagnosis?
Differentiate between other B cell neoplasms
- CLL B cells have a structural membrane defect which leads to the development of SMEAR CELLS on microscopy
How does Rawstron et (2017) diagnostic system differ from the Matutues scoring system?
- Also base don flow cytometry
Measures different cellular components
- kappa/lambda light chain
- CD5+/CD19+ (and CD20+, CD23+)
- CD200, ROR1 (and CD43, CD79b, CD81, CD10)
(FYI: better at discriminating between other B cell lymphoproliferative disorders such as Mantle cell lymphoma)
Describe how the characteristic of CLL cells in the lymph node, peripheral blood and bone marrow differ and the implications for treatment
Peripheral blood CLL cells
- good at surviving but do not proliferate
- react well to chemotherapy
Lymph node CLL cells
- high proliferative drive (receive proliferative signals from CD3+ T cells in LN as they are in close proximity. Known as Ki67 proliferating cells) THIS IS WHERE PROLIFERATION PRIMARILY TAKES PLACE
- good at surviving
- hidden in “protective hiding space”
Bone marrow CLL cells
- moderate proliferative drive
- hidden in “protective hiding space”
- resistant to chemotherapy
A good marker for CLL should….
- predict which patients are likely to progress
- predict which patients will respond to treatment
- be reproducible
- be cheap and easy to perform
(ideally also give information about the biology of the disease and represent a tractable therapeutic range)
Outline the Binet classification system
A
- 70% of cases
- mean survival >10 years
- no disease progression, don’t need treatment
B
- 20%
- mean survival: 5-7 years
- receive treatment if symptomatic
C
- 10%
- mean survival: 1-3 years
- require treatment
What is the prognosis of CLL?
1/3- wont progress, wont need treatment (Binet A)
1/3- indolent disease in the beginning, later progresses
1/3- aggressive disease which requires immediate treatment
