CLL

Question 1

epidemiology of chronic lymphocytic leukaemia

Answer 1

proliferation of mature B lymphocytes
commonest leukaemia in western world
Commonest cause lymphocytosis in elderly !
caucasian
mean age - 72
genetic predisposition

Question 2

lab findings for CLL

Answer 2

Lymphocytosis between 5 and 300 x 109/l – mature lymphocytes

Smear cells/smudge cells

Bone marrow failure:

• Normocytic normochromic anaemia
• Thrombocytopenia
• Bone marrow – Lymphocytic replacement of normal marrow elements

Question 3

immunophenotype of CLL

Answer 3

T cells in the periphery blood CD 5+ve and 19/20-ve
B-CLL – monoclonal abnormally CD 5 on B cells = CLL ie CD5 +ve B cell in peripheral blood

Question 4

natural history of CLL

Answer 4

5-10yr healthy then 2-3year terminal phase

1/3 never progress
1/3 Progress, respond to CLL Rx (death from unrelated disorder)
1/3 Progress, require multiple lines of Rx, refractory disease, death from CLL

Question 5

Px of CLL

Answer 5

Cell based prognostic factors
* IgHV mutation status ie whether it is pre or post germinal centre
* CLL FISH cytogenetic panel – chr status
* TP53 mutation status (Chromosome 17p del and/or TP53 point mutation)
* Deletion of 13q
* Trisomy 12
* Deletion of 11q (ATM)

Clinical staging systems
* Binet or Rai (clinical staging) - worse if marrow involvement
* CLL IPI score

Question 6

clinical issues with CLL

Answer 6

Question 7

supportive care for CLL

Answer 7

Sino-pulmonary infections
* Early Rx with antibiotics
* Pneumocystis prophylaxis (may also require zoster ppx)
* Recurrent infection + IgG < 5g/l > IVIG replacement therapy

Vaccinations
* Pneumococcal
* Sars CoV2
* Seasonal flu
* Avoid live vaccines

Question 8

when to treat CLL

Answer 8

indolent - only treat when indications:
Progressive lymphocytosis
* >50% increase over 2 months
* lymphocyte doubling time <6 months

Progressive marrow failure
* Hb < 100, platelets <100, neutrophils <1

Massive or progressive lymphadenopathy/splenomegaly
Systemic symptoms (B symptoms)
Autoimmune cytopenias (treat with immunosuppression not chemotherapy)

Question 9

treatment for CLL

Answer 9

Combination Immuno-chemotherapy (being superseded by targeted Rx)
Targeted Therapy
* BTK inhibitor (Ibrutinib)
* BCL2 inhibitor (venetoclax)
* PI3K inhibitor (idelalisib)

Cellular therapy only for relapsed high risk cases
* Allogeneic SCT
* CAR-T therapy (chimaeric antigen receptor T cells)

BTK
Prevent cells dying by increasing bcl-2 (anti-apoptotic)

Question 10

how does venetolax work

Answer 10

Orally active Bcl 2 inhibitor, permits apoptosis of CLL cells
In high risk CLL p53 mutated 85% response and maintained at greater than 1 year
Main risk – dramatic resolution in lymphocyte count – cells all die and releasae K, uric acid, phos, ca – die of tumour lysis sundrome – need hydration and titrate the dose up

Question 11

what is ibrutinib used for

Answer 11

Also effective in CLL p53 mutation cases
(well tolerated oral medication, no myelosuppression)