CLL

Question 1

what is the epidemiology of CLL

Answer 1

o Most common (UK = 4.2/100,000/year) leukaemia in West
o Tends to affect Caucasians
o Median age at presentation: 72 years (10% aged <55yo)
o Relatives have 7 x increased risk

Question 2

What are the lab findings in CLL

Answer 2

Lymphocytosis, smear cells, normocytic normochromic anaemia, thrombocytopaenia, bone marrow lymphocytic replacement of normal marrow elements

Question 3

Immunophenotyping of CLL

Answer 3

o	CD19 along Y axis and CD5 along X axis 
o	Normal Mature B Cells:
	CD19 POSITIVE
	CD5 NEGATIVE
o	Normal Mature T Cells:
	CD3 positive 
	CD4 or CD8 positive 
•	Th-cell 
•	CTL cell
	CD19 NEGATIVE
	CD5 POSITIVE
o	In CLL, the B cells continue to express CD5
o	This immunophenotyping assay shows a third population of lymphocytes co-expressing CD19 and CD5

Question 4

CLL prognostic factors

Answer 4

o	Clinical (quantify burden of malignant cells)
	Rai staging
	Binet staging (see picture right)
o	Lab/malignant cell based:
	Cytogenetics (FISH panel)
	Immunoglobulin gene mutation status 
•	IgH mutated
•	IgH unmutated (BAD)

Question 5

worst case scenario CLL

Answer 5

Binet stage C, IgH unmutated, 17p del / p53 mutated

Question 6

what is richter transformation

Answer 6

o Although this is an indolent disease, there is a 1% chance every year that CLL can acquire more mutations and undergo a RICHTER TRANSFORMATION (become a high grade lymphoma)

Question 7

why can CLL lead to autoimmune disease

Answer 7

deregulation of surviving normal b cell population

Question 8

what is car-T therapy

Answer 8

o CAR-T are autologous T cells that are modified to contain chimeric antigen receptors
o The internal portion of these receptors = signalling molecules
o External portion has been engineered to target CD19 antigens on surface of B cells
o Reinfuse patient with autologous engineered T cells  target and kill the B cells
o Leads to complete B cell depletion  not a problem provided that you give IVIG

Question 9

CLL treatment

Answer 9

vaccinations for flue etc. antiinfective prophylaxis e.g. acyclovir, treat high grade richter transformation, must irradiate blood products, alloginic stem cells transplant if young

Question 10

indication for treatment

Answer 10

• Progressive lymphocytosis (count doubling < 6 months)
• Progressive bone marrow failure (Hb < 100; Platelets < 100; Neutrophils < 1)
• Massive or progressive lymphadenopathy/splenomegaly
• Systemic symptoms (B symptoms)