chris pepper lecture 2

Question 1

what do we mean when we say CLL is a very heterogenous disease?

Answer 1

• it doesn’t affect some people at all
• it affects others very severely

there is a rule of 1/3rds

1. 1/3 will not develop sx
2. 1/3 some people will have indolent disease with disease progression later
3. 1/3 will have aggressive disease requiring tx immediately

Question 2

what are requirements for an ideal prognostic marker?

Answer 2

• be able to predict which patients will progress
• predict if they will respond to tx
• cheap and easy to preform
• must be reproducible

Question 3

which staging system is used for CLL in europe and US?

Answer 3

europe= binet

usa= rai

Question 4

for who are the clinical staging systems of binet and rai not useful and why?

Answer 4

• for those who present young and have early stage (A disease)
• this is because CLL is a very heterogenous disease so you will not know which stage A patients will progress and which stage A patients will remain asymptomatic

Question 5

what is the prognosis of stage A cll?

Answer 5

> 10 yrs

- tx is not requires

Question 6

what is the prognosis of stage B CLL?

Answer 6

5-7 yrs

- tx only if symptomatic

Question 7

what is the prognosis of stage C CLL?

Answer 7

1-3 yrs

- give tx

Question 8

what is the gold standard tx for CLL?

Answer 8

combination tx - FCR fludarabine. cyclophosphamide. rituximab.

Question 9

What can response to FCR Tell you about prognosis?

Answer 9

Those with reduced response to fcr have much worse outcomes at 5 years compared to those with complete responses

Question 10

what are different prognostic factors that can be evaluated for stage A cll?

Answer 10

1. LTD- lymphocyte doubling time
2. Cytogenetics
3. IGHV mutation- immunoglobulin gene mutation status (as a result of somatic hypermutation)
4. Cd38, Zap-70, cd49d- flow cytometry markers

Question 11

which factors are independently prognostic in early CLL disease?

Answer 11

• Age
• LTD
• IGHV mutation status
• CD49d

Question 12

how does IGHV mutation status relate to prognosis of CLL?

Answer 12

• Somatic hypermutation is a natural response to antigen challenge
• If malignant B cells don’t undergo SH and genes remain germline then patient will have poor outcome
• This is because the receptor will be less specific and will be more promiscuous binding to a number of antigens and therefore constantly promoting the tumour cell to proliferate

Question 13

what are the different flow cytometry markers and which is the best?

Answer 13

surface proteins
CD38, C49d the best markers- CD49d is the most prognostic

intracellular protein inside tumour b cell
ZAP-70

Question 14

what is the role of cytogenetics in prognosis and treatment of cll?

Answer 14

cytogenetics should be preformed prior to treatment- this is because it is established that patients with a 17p deletion or TP53 mutation have a vastly inferior outcome when given standard chemotherapy

px with infererior gene mutations require earlier tx and have lower overall survival

Question 15

which factors are not independent prognostics in early stage disease?

Answer 15

• CD38
• ZAP70
• cytogenetics

Question 16

what do prognostic tools ultimately allow for?

Answer 16

• risk adapted therapy

- personalised to px risk factors