Haematology 4 - Chronic myeloproliferative neoplasms

Question 1

What is the target of imatinib?

Answer 1

Mutated tyrosine kinase (by BCR-ABL gene)

Question 2

What is the normal role of janus kinases?

Answer 2

GF binds to receptors - activate JAK- they activate the STAT pathway, which promotes cell growth and replication
Associated with haemopoietic cells

Question 3

How does JAK2 mutation cause uncontrollable replication?

Answer 3

No longer need growth factor to activate

Question 4

In polycythaemia vera, what else will be abnormal on the FBC other than red cell count?

Answer 4

Pronounced thrombocytophilia and slight granulocytophilia

Question 5

Recall some symptoms of polycythaemia vera

Answer 5

Due to hyperviscosity: 
- Headaches
- visual disturbances
- dyspnoea, fatigue
Due to increased histamine release: 
- peptic ulcer
- aquagenic pruritis
Other:
- Plethora
- Erythromelalgia (red, painful extremities) 
- Gout
- Retinal vein engorgement

Question 6

What is the expected level of erythropoietin in polycythaemia vera?

Answer 6

Low

Question 7

What mutation is present in all patients with polycythaemia vera?

Answer 7

JAK2 V617F

Question 8

What do you see in BM trephine biopsy in PV?

Answer 8

• increased cellularity
• megakaryocyte abnormality
• increase in reticulin fibres

Question 9

How should pseudopolychthaemia and polycythaemia vera be differentiated?

Answer 9

Isotype dilution method

- Polycythemia will have increased plasma, pseudo will have decreased

Question 10

Recall 3 causes of increased EPO

Answer 10

Hypoxia
Uterine myoma
Renal cancer

Question 11

Recall 3 causes of pseudopolycythaemia

Answer 11

Alcohol
Obesity
Diuretics

Question 12

Recall 3 ways in which polycythaemia vera can be treated

Answer 12

1. Venesection (keep HCT <45%)
2. Cytoreductive therapy
3. Aspirin to reduce thrombosis risk (keep plts <400 x 10^9/l)

Question 13

What is idiopathic erythrocytosis?

Answer 13

An isolated erythrocytosis with low EPO, where JAK2 V617 mutation is absent (although JAK mutation in exon 12 may be present)

Question 14

How should idiopathic erythrocytosis be treated?

Answer 14

Venesection only

Question 15

What is the diagnostic criteria for essential thrombocytothaemia?

Answer 15

• Chronic myeloproliferative neoplasm with a sustained thrombocytosis > 600 x 10^9/L
• megakaryocyte clustering and abnormality
• no evidence of reactive thrombocytosis
• no other myeloproliferative disorder
• JAK2 V617F mutation (60%)

Question 16

Which age group is most at risk of essential thrombocytothaemia?

Answer 16

Bimodal:
Small peak at 30y (M=F)
Larger peak at 55y (F>M)

Question 17

What are the presentations for patients with essential thrombocytothaemia?

Answer 17

Thrombosis or bleeding?? paradoxically

Minor : headache, dizziness, visual disturbance, small splenomegaly

Question 18

Is there a JAK2 mutation in essential thrombocytothaemia?

Answer 18

Yes in 60%

Question 19

What is the treatment for essential thrombocytothaemia?

Answer 19

1st line: Hydroxycarbamide (suppresses other cells too)
2nd line: anagreline (specific inhibition of plt formation - but SE = palpitation, flushing, increased risk of myelofibrosis)
Aspirin

Question 20

Which condition is “tear drop poikilocytosis” pathognemonic of?

Answer 20

Myelofibrosis

Question 21

What is seen in BM trephine biopsy in myelofibrosis?

Answer 21

• dry tap
• increased reticulin and collagen fibres
• prominent megakaryocyte hyperplasia and clustering
• new bone formation

Question 22

Which cells are hyperproliferating in myelofibrosis?

Answer 22

Mostly megakaryocytes and granulocytes

Question 23

Recall signs and symptoms of myelofibrosis

Answer 23

Massive spleen
Anaemia, thrombocytopenia/thrombocytosis
Hepatomegaly
Hypermetabolic state - wt loss, fatigue, dyspnoea, night sweats, hyperuricaemia

Question 24

What is the treatment for myelofibrosis?

Answer 24

Supportive: RBC and plt transfusion
Hydroxycarbamide for thrombocytosis (may worsen anaemia)
Ruxolotinib - a JAK2 inhibitor
Allogenic stem cell transplant
Splenectomy (symptomatic relief but will worsen condition)

Question 25

What are the bad prognosis signs in myelofibrosis?

Answer 25

• severe anaemia (<10g/dl)
• thrombocytopenia ( <100 x 10^9/l)
• massive splenomegaly

Question 26

Recall 3 bad prognostic indicators in CLL

Answer 26

LDH raised
CD38+
11q23 deletion

Question 27

Recall 3 good prognostic indicators in CLL

Answer 27

Hypermutated Ig gene
Low ZAP-70 expression
13q14 deletion

Question 28

What is the 1st line treatment for CLL with a p53 deletion?

Answer 28

Ibrutinib