Symposia: CLL

Question 1

What is leukaemia?

Answer 1

A form of blood cancer that arises due to a failure of haematopoietic differentiation

Question 2

How is CLL diagnosed?

Answer 2

1. Enlarged lymph nodes, and anaemia and/or bruising resulting from a low platelet count.
2. Lymphocytes expressing CD5+ and CD19+ antigens!!!
3. Additional protein markers: CD200, CD43, and ROR1.

Question 3

What are the key prognostic tools used in the management of CLL?

Answer 3

1. Binet/Rye Clinical Staging
2. Lymphocyte doubling time (LDT)
3. Immunoglobulin heavy chain gene mutation status
4. CD38 expression
5. CD49d expression (integrin which modulates adhesion quality of cells; high CD49d means cells can migrate and have a worser prognosis)
6. Detection of P53 mutation or deletion

Question 4

What are the features of Stage A CLL?

Answer 4

Confirmed diagnosis of CLL with a CD5+/CD19+ lymphocytosis of
>5 x 109/L

Question 5

What are the features of Stage B CLL?

Answer 5

Same as Stage A PLUS at least 3 areas of palpable lymphoid tissue
enlargement

Question 6

What are the features of Stage C CLL?

Answer 6

Same as Stage B PLUS Haemoglobin <100g/L or Platelet count <100/µL (both signify some degree of bone marrow failure).

Question 7

What are the standard treatment options for patients with CLL?

Answer 7

Chemotherapy- typically targets DNA of rapidly dividing cells.
Chemoimmunotherapy- immunoglobulin antibody (Rituximab) which target CD20

Question 8

Why is P53 important for the prognosis of CLL?

Answer 8

P53 is important in

determining the cellular response to DNA damage (including chemotherapy). Deletion or mutation confers poorer prognosis.

Question 9

What are the first line treatment options for “fit”* patients without a P53 deletion/mutation?

Answer 9

Fludarabine + cyclophosphamide + rituximab (FCR)
or
Bendamustine + rituximab (BR)

Question 10

What are the first line treatment options for “less fit” patients without a P53 deletion/mutation?

Answer 10

Chlorambucil + rituximab (CR)
or
Bendamustine + rituximab (BR)

Question 11

What is rituximab?

Answer 11

Rituximab is a monoclonal antibody targeting CD20

Question 12

What are the novel therapies for CLL?

Answer 12

1. Ibrutinib (BTK inhibitor)
2. Idelalisib (PI3K inhibitor)
3. Venetoclax (BCL2 inhibitor)

Question 13

What are the first line treatment options for patients with a P53 deletion/mutation?

Answer 13

Ibrutinib and venetoclax

Question 14

What are the side effects of Ibrutinib?

Answer 14

Non-curative and causes a transient increase in peripheral blood lymphocytosis

Question 15

What is CAR T?

Answer 15

Chimeric antigen receptor T cells

Question 16

How does CAR T work?

Answer 16

CAR-T cell therapy uses T cells engineered with CARs for cancer therapy. T cells are modified to recognize cancer cells, especially CD19 on the surface of the tumour, in order to more effectively target and destroy them.