Myeloproliferative disorders

Question 1

What is the main difference between the myeloproliferative disorders (MPD) and leukaemia?

Answer 1

Maturation is relatively preserved in MPD

Question 2

Over-produtction of granulocytes and their precursors

Answer 2

Chronic myeloid leukaemia (CML)

Question 3

When should an MPD be considered as a diagnosis? (3)

Answer 3

When there is high myeloid cell count, with splenomegaly, and no reactive explanation for this

Question 4

Three phases of CML

Answer 4

Chronic phase (months to years, few symptoms)
Accelerated phase (increasing symptoms and spleen size)
Blast crisis (features of acute leukaemia)

Question 5

What is the pathological hallmark of CML?

Answer 5

Philadelphia chromosome; reciprocal translocation between long arms of chromosome 9 and 22

Question 6

What does the Philadelphia chromosome (Ph) produce?

Answer 6

BCR-ABL1- abnormal tyrosine kinase

Question 7

Clinical features of CML (3)

Answer 7

Splenomegaly
Hypermetabolic symptoms
Gout

Question 8

What is the targeted treatment for Ph+ve CLM?

Answer 8

Imatinib- tyrosine kinase inhibitor

Question 9

Three main BCR-BL1 negative MPDs

Answer 9

Polycythaemia rubra vera
Essential thrombocythaemia
Idiopathic myelofibrosis

Question 10

Features that are common to MPDs (8)

Answer 10

May be asymptomatic
Gout
Fatigue
Weight loss
Sweats
Splenomegaly
Marrow failure
Thrombosis

Question 11

What causes marrow failure in MPD?

Answer 11

Fibrosis or leukaemic transformation

Question 12

Distinguishing feature of polycythaemia rubra vera

Answer 12

High Hb and haematocrit

Question 13

Causes of secondary polycythaemia (3)

Answer 13

Chronic hypoxia
Smoking
EPO-secreting tumour

Question 14

Main cause of pseudopolycythaemia

Answer 14

Dehydration

Question 15

Other than common features of MPD, what are the symptoms of PRV?

Answer 15

Headache
Fatigue
Aquagenic pruritus

Question 16

Mutation present in 95% patients with PRV

Answer 16

JAK2 point mutation causing uninhibited activation of erythrypoiesis

Question 17

Treatment of PRV (3)

Answer 17

Venesection to Hct

Question 18

Uncontrolled production of abnormal platelets

Answer 18

Essential thrombocythaemia

Question 19

Manifestation of ET (2)

Answer 19

Thrombosis

At high levels can cause bleeding

Question 20

What should be excluded in a patient with high platelet count? (2)

Answer 20

A reactive thrombocytosis, or CML

Question 21

What are the typical causes of a reactive thrombocytosis? (4)

Answer 21

Blood loss
Inflammation
Malignancy
Iron deficiency

Question 22

Mutations in ET (3)

Answer 22

JAK2 (in 50%)
CALR
MPL

Question 23

Treatment of ET (2)

Answer 23

Anti-platelets
Cytoreductive therapy (hydroxycarbamide, interferon alpha)

Question 24

What are the underlying aetiologies of myelofibrosis? (2)

Answer 24

Idiopathic

Transformation from PRV or ET

Question 25

Features of idiopathic myelofibrosis (4)

Answer 25

Bone marrow fibrosis on biopsy Extramedullary haemopoiesis causing hepato/splenomegaly Leucoerythroblastosis Teardrop RBCs in blood film

Question 26

Causes of a leucoerythroblastic film (3)

Answer 26

Reactive (sepsis) Marrow infiltration Myelofibrosis

Question 27

Treatment of MF (2)

Answer 27

``` Marrow support Allogeneic SCT (selected patients) ```