Chronic myeloproliferative disorders and chronic myeloid leukaemia

Question 1

Chronic Myeloproliferative Disorders

Answer 1

• Myeloid progenitor stem cell disorders of the bone marrow

- develop into AML in ~10%

Question 2

Polycythaemia Vera (PV)

Answer 2

• Increased RBC’s

- All ages, peak = 50-70

Question 3

Clinical features of PV

Answer 3

• Itching
• Gout (in RBC turnover = increased uric acid)
• Gangrene (increased thrombosis)
• Splenomegaly

Question 4

Diagnosis of PV

Answer 4

• Persistent increased Hb
• Test for JAK2 mutation
• ## Low EPO levels

Question 5

Treatment of PV

Answer 5

• Aspirin for thrombosis risk
• Venesection
• Good prognosis but risk of AML

Question 6

Essential Thrombocytosis (ET)

Answer 6

• Increased platelet count causing clusters in the bone marrow
• Distinguished from reactive thrombocytosis = platelets released by stress

Question 7

Diagnosis of ET

Answer 7

• Persistent platelets >450

- Test for JAK2 and CALR

Question 8

Treatment of ET

Answer 8

• Assess thrombosis risk, antiplatelet treatment

- Cytoreduction - hydroxycarbamide

Question 9

Idiopathic Myelofibrosis (IMF)

Answer 9

• Bone marrow scarring

- Ineffective cell production causing low blood count/cytopenia and splenomegaly

Question 10

Clinical features of IMF

Answer 10

• Pancytopenia - Low RBCs, white blood cells and platelets
• Massive splenomegaly
• Night sweats, fever, weight loss

Question 11

Diagnosis of IMF

Answer 11

• Tear shaped RBC’s
• Bone marrow biopsy
• JAK2 mutation or CALR mutation

Question 12

Treatment of IMF

Answer 12

• JAK2 inhibitors
• Bone marrow transplant and radiotherapy to shrink spleen
• Prognosis is poor with 5 year mean survival

Question 13

Causes of Splenomegaly = CHICAGO

Answer 13

C = cancer (of the spleen
H = haematological – MF, CML, CLL
I = infection - schistosomiasis, malaria, leishmaniasis, EBV
C = congestion – cirrhosis/portal HT
A = autoimmune – haemolysis, SLE
G = glycogen storage disorders
O = other – amyloid, sarcoid

Question 14

Chronic Myeloid Leukaemia

Answer 14

• neoplasm of myeloid progenitor cells causing leucocytosis in the blood
• Presence of myelocytes - shouldn’t usually be in blood

Question 15

Clinical features of Chronic Myeloid Leukaemia

Answer 15

• Histology = leucocytosis, leucoerythroblastic (immature WBCs), anaemia (low RBCs because too many WBCs)
• Signs = splenomegaly
• Symptoms = abdominal discomfort (due to splenomegaly), fatigue (anaemia), venous occlusion (e.g. DVT), gout (hyperuricaemia), retinal haemorrhages

Question 16

Aetiology of Chronic Myeloid Leukaemia

Answer 16

• Chr t(9;22) translocation – Philadelphia chromosome

- Excess proliferation within the myeloid lineage

Question 17

Treatment of Chronic Myeloid Leukaemia

Answer 17

• Chronic phase = Gleevec/imatinib (BCR-ABL TK Inhibitor)

- Acute phase (presents similar to AML) = intensive chemo + BM transplant