CLL

Question 1

definition of chronic lymphocytic leukaemia (CLL)

Answer 1

characterised by progressive accumulation of functionally incompetent B lymphocytes - monoclonal

overlap between CLL and non-hodgkin’s definition

Mutations, trisomies, and deletions (eg del17p13) in fl uence risk

Question 2

aetiology of CLL

Answer 2

malignant cells accumulate because they cannot undergo apoptosis - because of overexpression of BCL-2 and Fas-inhibitory molecules eg TOSO

chromosomal changes include:

• trisomy 12,
• 11q and 13q deletions

both BCL-2 (proto-onchogene) and p53 (tumour suppressor gene) contribute to biologic behaviour of B-CLL cells

overexpression of microRNAs (small non-coding RNSa that modulate the expression of genes at the post-transcriptional level) may predispose to CLL

Question 3

epidemiology of CLL

Answer 3

90% are >50

female more

rare in Asian

commonest cause of leukaemia

incidence 5/100000/yr

Question 4

sx of CLL

Answer 4

asymtomatic - 40-50% picked up on routine blood count

systemic sx - lethargy, malaise, night sweats

sx of bone marrow failure:

• recurrent infections - bacterial, viral, fungal
• herpes zoster
• easy brusing/bleeding eg epistaxis

assess performance status and co-morbidities

weight loss, sweats, anorexia if severe

Question 5

signs of CLL

Answer 5

enlarged, rubbery, non-tender lymphadenopathy (often symmetrical)

hepatomegaly

splenomegaly

later stages/signs of bone marrow failure:

• pallor - anaemia
• cardiac flow murmur
• purpura/ecchymoses

Question 6

Ix for CLL

Answer 6

CLL may be associated with autoimmune phenomena - haemolytic anaemia (10%), thrombocytopaenia or a combination of both (Evan’s syndrome)

blood

• FBC - gross lymphcytosis (5-300x10(9)/L)
• anaemia - due to bone marrow infiltration, hypersplenism, or autoimmune haemolysis
• low plt
• low neutrophils
• low serum Ig

blood films - small lymphocytes with thin rims of cytoplasm and smudge/smear cells

bone marrow aspirate or biopsy

cytogenics - provides prognostic info

CT CAP - on basis of sx

Question 7

bone marrow aspirate or biopsy for CLL

Answer 7

lymphocytic replacement (25-95%) of normal marrow elements

immunophenotyping shows the malignant cell to be a relatively mature B cell with weak surface expression of monoclonal IgM or IgD (Kappa or lambda light chain only)

T cell varients of CLL are much rarer but more aggressive

hairy cell leukaemia is a low grade CLL variant with good prognosis showing monoclonal proliferation of hairy B cells in blood, bone marrow and liver

Question 8

2 staging systems for CLL

Answer 8

Rai

Binet

Question 9

Rai staging system for CLL

Answer 9

0 Lymphocytosis.

I Above, plus lymphadenopathy.

II Above, plus organomegaly (hepatomegaly or splenomegaly).

III Above, plus anaemia (Hb < 10 g/dL).

IV Above, plus thrombocytopaenia (platelets < 100 109 /L).

Question 10

binet staging for CLL

Answer 10

A < 3 lymphoid areas (neck/axilla/groin lymph nodes, liver or spleen involvement).

B > 3 lymphoid areas.

C Anaemia and/or thrombocytopaenia.

Question 11

natural history of CLL

Answer 11

1/3 never progfress

1/3 progress slowly

1/3 progress actively

CD23 adn B2 microglobin correlate with bulk of disease and rate of progression

death is due to infection or transformation to aggressive lymphoma (Richter’s syndrome)