Haematology

Question 1

What B Cells express CD 20

Answer 1

Everything except stem cell, pre B Cell and plasma cells

Question 2

Diagnosis of Chronic Lymphocytic Leukaemia?

Answer 2

Smudge Cells on film
>95% are B phenotype
Co expression of CD5+, CD 19 and CD 23

Question 3

What subtype of lymphocytic leukaemia doesn’t express CD23

Answer 3

Mantle Cell

Question 4

Common symptoms of CLL?

Answer 4

Generalised lymphadenopathy, fatigue, weight loss, 60% asymptomatic

Question 5

What is the traditional CLL staging system?

Answer 5

Binet

Stage C or severe is haemoglobin less than 100 or platelets less than 100

Question 6

Poor prognostic markers in CLL?

Answer 6

Increased beta 2 microglobulin
Increased LDH
Unmutated IgVH (which implies they are immature cells, they haven’t entered secondary lymph node for hypermutation
FISH markers (17p deletion WORST) median 3 yr survival

Question 7

What are good and poor prognostic FISH in CLL?

Answer 7

17p deletion worst prognosis with median 3 year survival. essentially translates to a deletion of p53
This gives resistance to traditional Chemo (Fludarabine and Cyclophosphamide)

Favourable: deletion 13q, median 12 year survival

Question 8

What are some of the clinical features of progression

Answer 8

Autoimmune complications (>10%) such as autoimmune haemolytic anaemia, immune thrombocytopaenia purpura
Non melatomous skin cancers
Rising lmphocytosis
Increasing lymphadenopathy and splenomegaly
Progressive BM failure
Progressive immuneparaesis and B cell suppression
Secretion of a paraprotein

Question 9

When do you commence treatment of CLL?

Answer 9

If advanced stage, progressive lymphadenopathy or cytopaenias

Question 10

What is CLL treatment for normal patients?

Answer 10

Rituximab, fludarabine and cyclophosphamide first line

Question 11

What is CLL treatment for frail patients?

Answer 11

Obinutuzumab (Type II anti CD-20 with enhanced ADCC) + chlorambucil

Question 12

What is CLL treatment for relapsed patients?

Answer 12

Oral enzyme inhibitors
Butons tyrosine kinase inhibitor: ibrutinib
PI3 kinase inhibitor: Idealisib

Question 13

What is ibrutinib and how does it work?

Answer 13

Blocks brutons tyrosine kinase
This blocks BCR signalling/activation. Induces apoptosis, blocks migration /adherance

Strict criteria for suitability on PBS: based on age, frailty and also 17p deletion

Question 14

How does Idelalisib work?

Answer 14

Oral inhibitor of phosphoinositide 3-kinase (PI3K)

Can only be used in CLL relapsed patients

Question 15

What are the side effects of Idelalisib

Answer 15

colitis 20%, transaminitis 15%, increased death secondary to infections

Question 16

What is Venetoclax?

Answer 16

BH3 mimetic, binds to excess BCL2 and restores cells ability to undergo apoptosis
Results in immediate tumour lysis and thus huge tumour lysis syndrome implications
Thus dose needs to be ramped up slowly

Approved for relapsed or refractory CLL with 17 p deletion