Symposia: CLL Flashcards
What is leukaemia?
A form of blood cancer that arises due to a failure of haematopoietic differentiation
How is CLL diagnosed?
- Enlarged lymph nodes, and anaemia and/or bruising resulting from a low platelet count.
- Lymphocytes expressing CD5+ and CD19+ antigens!!!
- Additional protein markers: CD200, CD43, and ROR1.
What are the key prognostic tools used in the management of CLL?
- Binet/Rye Clinical Staging
- Lymphocyte doubling time (LDT)
- Immunoglobulin heavy chain gene mutation status
- CD38 expression
- CD49d expression (integrin which modulates adhesion quality of cells; high CD49d means cells can migrate and have a worser prognosis)
- Detection of P53 mutation or deletion
What are the features of Stage A CLL?
Confirmed diagnosis of CLL with a CD5+/CD19+ lymphocytosis of
>5 x 109/L
What are the features of Stage B CLL?
Same as Stage A PLUS at least 3 areas of palpable lymphoid tissue
enlargement
What are the features of Stage C CLL?
Same as Stage B PLUS Haemoglobin <100g/L or Platelet count <100/µL (both signify some degree of bone marrow failure).
What are the standard treatment options for patients with CLL?
Chemotherapy- typically targets DNA of rapidly dividing cells.
Chemoimmunotherapy- immunoglobulin antibody (Rituximab) which target CD20
Why is P53 important for the prognosis of CLL?
P53 is important in
determining the cellular response to DNA damage (including chemotherapy). Deletion or mutation confers poorer prognosis.
What are the first line treatment options for “fit”* patients without a P53 deletion/mutation?
Fludarabine + cyclophosphamide + rituximab (FCR)
or
Bendamustine + rituximab (BR)
What are the first line treatment options for “less fit” patients without a P53 deletion/mutation?
Chlorambucil + rituximab (CR)
or
Bendamustine + rituximab (BR)
What is rituximab?
Rituximab is a monoclonal antibody targeting CD20
What are the novel therapies for CLL?
- Ibrutinib (BTK inhibitor)
- Idelalisib (PI3K inhibitor)
- Venetoclax (BCL2 inhibitor)
What are the first line treatment options for patients with a P53 deletion/mutation?
Ibrutinib and venetoclax
What are the side effects of Ibrutinib?
Non-curative and causes a transient increase in peripheral blood lymphocytosis
What is CAR T?
Chimeric antigen receptor T cells