Chronic Lymphocytic Leukaemia without cards on lymphoma Flashcards
What is chronic lymphocytic leukaemia?
Proliferation of mature B-lymphocytes.
Commonest leukaemia in the western world. Caucasian.
Age at presentation median 72 (10% <55y)
Relatives x7 increased incidence
What are 5 common laboratory features of CLL?
Lymphocytosis: 5-300 x 10^9/l
Smear cells
Normocytic normochromic anaemia
Thrombocytopenia
BM: Lymphocytic replacement of normal marrow elements
What is the timecourse of CLL?
Highly variable natural hx:
- Initially 5-10y good health until progression to a 2-3y terminal phase.
- Rapid progression to death within 2-3y.
In a disorder of elderly:
- 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
What are prognostic features of CLL and how is it staged?
Cell based prognostic factors:
* TP53 mutation status (Chr 17p del +/- TP53 point mutation)
* IgHV mutation status
* CLL FISH cytogenetic panel
Clinical staging systems:
* Binet or Rai (clinical staging)
* CLL IPI score
Give 3 bad prognostic indicators in CLL
LDH raised
CD38 +ve
11q23 deletion
Give 3 good prognostic indicators in CLL
Mutated IgHV
Low ZAP-70 expression
13q14 deletion
What is the median survival of CLL?
- Mutated: 25y
- Unmutated: 8y
What are clinical complications with CLL?
Population of malignant (non functional) mature B cells+ hypogammaglobulinaemia: Increased risk of infection
Proliferate within BM (efface): BM failure
Circulate to nodes, spleen + blood: Lymphadenopathy+/ splenomegaly, lymphocytosis
Acquire further mutations: Transform to high grade lymphoma; Richter Transformation (1% per year)
Disease of immune cells: AI complications e.g. Immune haemolytic anaemia
How can sino-pulmonary infections in CLL be treated?
Early Rx with abx
Pneumocystis prophylaxis (may also require zoster ppx)
Recurrent infection + IgG < 5g/l : IVIG replacement therapy
Which 3 vaccinations should be offered to patients with CLL?
Pneumococcal
Covid19
Seasonal flu
Avoid live vaccines
Watch and wait is the preferred approach to CLL.
When should treatment be given?
Progressive lymphocytosis:
- >50% Increase over 2m
- Lymphocyte doubling time <6m
Progressive BM failure:
- Hb < 100, platelets <100, neutrophils <1
Massive or progressive lymphadenopathy/splenomegaly
Systemic Sx
AI cytopenias (treat with immunosuppression not chemo)
What therapy can be offered for CLL patients?
Combination Immuno-chemotherapy (being superseded by targeted Rx)
Targeted Therapy:
- BTK inhibitor
- BCL2 inhibitor
Cellular therapy only for relapsed high risk cases:
- Allogeneic SCT
- CAR-T therapy
Which BTK inhibitor can be used to treat CLL?
Ibrutinib (BTK)
Idelalisib (PI3K)
Which BCL2 inhibitors can be used to treat CLL?
Venetoclax
Which experimental cell based therapies can be used to treat CLL?
Chimeric Antigen Receptor T cells (CAR-T)