Chronic Lymphocytic Leukaemia

Question 1

Notes on epidemiology, common symptoms, and diagnosis of CLL

Answer 1

**Epidemiology
**> 70 years, Western World, rare familial clusters

**Common symptoms
**Lymphadenopathy, fatigue, weight loss. 60% asymptomatic at diagnosis

**Diagnosis
**Small, amture lymphocytosis. *Smudge cells on film
*Co-expression of CD5, CD 19, CD 23
- CD23 helps distinguish CLL from leukaemic manifestation of mantle cell lymphoma

Question 2

Traditional CLL staging system and poor prognostic markers

Answer 2

**Staging system
**Binet

**Poor prognostic markers
**Increased B2 microglobulin
Increased LDH
Unmutated IgH (adverse) - not readily available Aus/NZ
Molecular/chromosomal markers
- *17p deletion -> confers resistance to traditional chemo
*CLL cells which have not entered the germinal centres and haven’t undergone the “hypermutation” of the IgVH -> much poorer prognosis that those that have undergone activation process

• del 13q == favourable prognosis (Generally don’t do FISH in newly diagnosed - done when progressive disease or rapid deterioration)

Question 3

Clinical course CLL

Answer 3

• Rising lymphocytosis
• Increasing lymphadenopathy and splenomegaly
• Progressive BM failure
• Progressive immuneparesis and B cell immunosuppression
• Secretion of a paraprotein
• Autoimmine complications (>10%) -> autoimmune haemolytic anaemia, ITP
• Secondary skin cancers - non-melanoma

Question 4

Indications for treatment CLL

Answer 4

• Anaemia or thrombocytopaenia <100
• > Massive or progressive/symtomatic splenomegaly/lymphadenopathy
• Progressive lymphocytosis (>50% rise over 2 months or LFT < 6 months)
• > AIHA or ITP unresponsive to steroids
• Symptomatic extranodal involvement
• Constitutional symptoms

Question 4

Options for treatment of CLL

Answer 4

**< 60 years
**Rituximab, fludarabine, cyclophosphamide
Exception: 17p deletion -> ibrutinib (Aus), venetoclax (NZ)

**Frail elderly
**Obinutuzumab (Type II anti-CD20 mab with enhanced ADCC) +Chlorambucil

Question 5

Notes on venetoclax

Answer 5

= BH3 mimetic (BCl 2 inhibitor) -> BCL2 overexpression confers resistance to apoptosis. Venetoclax restores cell’s abaility to undergo apoptotic death
Graduated oral dosing to reduce risk of tumour lysis