Cancer 1: Intro to Cancer Flashcards
what is leukemia ?
A blood cancer which arises due to failure of haematopoietic differentiation
What characterises CLL?
Clonal disorder of mature CD5+/CD19+ B cells Tumour in bone marrow, blood & 2o lymphoid tissue Immune dysfunction Infection Autoimmunity BM failure Highly variable outcomes. Incurable with current treatments
How would a patient present with CLL?
often discovered on blood test - may be asymptomatic enlarged LN repeat infections night sweats and fever enlarged sleep weight loss anaemia
how is CLL diagnosed ?
Traditionally CLL diagnosed using the Matutes scoring system
CLL when patients B cells express 4 or 5 of these Antigens such as CD5 CD23 and CD19
Cells small lymphocytes with very little cytoplasm
Smudge cells key indication of blood film.
The problem with the matutes system is that it is difficult to always be sure as non-hodgkin lymphoma’s in leukaemic phase could have a similar phenotype.
Therefore a new system has been bough in:
Clonal so they all express either the kappa or lambda light chain
Important to remember they are CD5/CD19 positive B cells and CD5 is usually a T cell Antigen.
what are the 3 compartments in which CLL reside?
LN: Survival
Proliferation
Protective niche ‘hiding place’
BM: Survival
Proliferation
Protective niche ‘hiding place’
Peripheral blood: Survival
No proliferation
More susceptible to apoptosis
What is the prognosis of CLL?
CLL is a very heterogenous disease
Some patients need little or no treatment
Some patients will die rapidly without medical intervention
What is the rule of thirds?
1/3 have aggressive disease
1/3 later disease progression
1/3 never need treatment.
What are the requirements of a good prognostic marker?
Marker(s) that will predict whether patients will respond to treatment
Preferably cheap and easy to perform
must be reproducible
Marker(s) should tell us something about the biology of the disease and preferably represent a tractable therapeutic target.
Describe the staging system for CLL?
Binet staging A/B/C
A requires no treatment
B requires treatement only if symptomatic
C requires treatment
why is clinical staging not enough?
extremely variable clinical course
clinical stage poorly prognostic for early stage (~70%) and for younger patients
new therapeutic approaches now available - MoAbs, biologics, combinations
describe the role of the IGHV mutation status
the B cell receptors do not undergo somatic hypermutation and therefore are moRE promiscuous and have better prognosis if you have the mutation
give some examples of some flow cytometry markers?
CD38
CD49d
ZAP70
what is standard treatment for CLL?
if fit without mutation
Chemo + antibodies
if they are fit without a 17p del
FCR/ BR/FR/PCR
what is standard treatment for CLL?
if older/unfit without mutation
chemo +antibodies
BR
what are the goals of novel therapies
develop targeted treatment for toxic cells.
recruit the immune system to fight
help improving the effect of existing disease
induce longer remission
