Myeloproliferative disorders

Question 1

Myeloproliferative neoplasms are associated with acquired mutations of genes that encode tyrosine kinases or kinase-associated proteins such as?

Answer 1

• primarily JAK2
• CALR
• MPL (the receptor for thrombopoietin)

Question 2

Polycythaemia is defined as?

Answer 2

an increase in the Hb concentration above the upper limit of normal for the patient’s age and sex

Question 3

what is absolute polycythaemia?

Answer 3

or erythrocytosis, red cell mass (volume) is raised greater than 125% of that expected for body mass and gender
note: the plasma volume is normal

Question 4

what is relative polycythaemia/ pseudopolycythaemia?

Answer 4

the red cell volume is normal but the plasma volume is reduced

Question 5

If the haematocrit is higher than 0.60 there will always be a raised red cell mass and absolute polycythaemia. T or F.

Answer 5

True

Question 6

which features indicate that erythrocytosis is likely?

Answer 6

A Hb >185 g/L or haematocrit >0.52 in men or
Hb >165 g/L or haematocrit >0.48 in women, indicates that erythrocytosis is likely

Question 7

what are the types of absolute polycythaemia?

Answer 7

• primary polycythaemia (includes both rare congenital causes of polycythaemia related to genetic changes in oxygen sensing or erythropoietin signalling, and the more common acquired myeloproliferative neoplasm polycythaemia vera)
• secondary polycythaemia (the bone marrow is driven by an increase in erythropoietin as a result of factors such as smoking, sleep apnoea or altitude)

Question 8

what is polycythaemia vera?

Answer 8

in PV, the increase in red cell volume is caused by clonal malignancy of a marrow stem cell
note: 95% of patients have the JAK2 V617F mutation

Question 9

what is the WHO major criteria for diagnosing PV?

Answer 9

• Hb > 16.5 g/dl in men; > 16 g/dl in women or
  PCV > 0.49 in men; > 0.48 in women or
  Increased red cell mass
• JAK2 mutation
• bone marrow biopsy revealing hypercellularity with trilineage growth

Question 10

what’s the WHO minor criterion for diagnosing PV?

Answer 10

low serum erythropoietin

Question 11

Diagnosis of PV requires meeting how many criteria?

Answer 11

Diagnosis of PV requires meeting either all three major criteria, or the first two major criteria and the minor criterion

Question 12

Criteria #2 (BM) is not required in diagnosis if?

Answer 12

Criteria #2 (BM) not required if Hb > 18.5 g/dl / PCV > 0.55 in men; Hb >16.5 g/dl / PCV > 0.49 in women and JAK 2 present and EPO levels low.

Question 13

PV is usually a disease of older people and has an equal sex incidence. T or F?

Answer 13

True

Question 14

what are the clinical features of PV?

Answer 14

• Headaches, dyspnoea, blurred vision and night sweats.
• Generalised pruritus, characteristically after a hot bath or shower
• Plethoric appearance: ruddy cyanosis, conjunctival suffusion and retinal venous engorgement.
• Splenomegaly in 75% of patients
• haemorrhage or thrombosis
• gout

Question 15

what are the lab findings of PV?

Answer 15

• haemoglobin, haematocrit and red cell count are increased. The total red cell volume is increased.
• neutrophil and basophils may increase
• platelet count may increase
• A JAK2 mutation is present in the bone marrow and peripheral blood granulocytes in over 95% of patients.
• The bone marrow is hypercellular with trilineage growth- trephine biopsy
• Serum erythropoietin is low.
• Plasma urate is often increased; the serum LDH is normal or slightly raised.
• Circulating erythroid progenitors are increased
• chromosome abnormalities are found in the minority

Question 16

TP53 and RUNX1 mutations predict for transformation to what?

Answer 16

AML

Question 17

how is PV treated?

Answer 17

• venesection- to reduce haematocrit <0.45
• hydroxycarbamide (hydroxyurea)
• Jak inhibitors (ruxolitinib)
• α-interferon
• low-dose aspirin
• ACE inhibitors
• radioactive phosphorus
• allopurinol

Question 18

what is the aim of treatment for PV?

Answer 18

The haematocrit should be strictly maintained below 0.45 and the platelet count below 600 and ideally below 400×10^9/L

Question 19

what is essential thrombocythaemia (ET)?

Answer 19

in this condition there is a sustained increase in the platelet count due to megakaryocyte proliferation and overproduction of platelets

Question 20

The haematocrit is normal and the Philadelphia chromosome or BCR-ABL1 rearrangement is present in ET. T or F.

Answer 20

False
the Ph chromosome is absent in ET

Question 21

What is the central diagnostic feature in ET?

Answer 21

A persisting platelet count of greater than 450 × 10^9/L is the central diagnostic feature

Question 22

What is the major criteria for diagnosis of ET?

Question 23

what is the minor criteria for diagnosis of ET?

Question 24

what are the clinical and laboratory findings?

Question 25

what are causes of a raised platelet count other than any myeloproliferative disorder?

Answer 25

• haemorrhage, trauma, post-op
• chronic iron deficiency
• malignancy
• chronic infections
• connective tissue diseases (eg. rheumatoid arthritis)
• post-splenectomy

Question 26

what classifies a high-risk patient with ET?

Answer 26

Patients at high risk include those over 60 years of age, and/or with previous thrombosis and/or with platelet count >1500 × 109/L

Question 27

how is a low risk patient with ET treated?

Answer 27

with low dose aspirin at 75 mg/day

Question 28

how is a high risk patient with ET treated?

Answer 28

with hydroxycarbamide

Question 29

what is primary myelofibrosis (PMF)?

Answer 29

progressive generalised reactive fibrosis of the BM in association with megakaryocytic atypic and proliferation with the development of haemopoiesis in the spleen and liver

Question 30

what are the clinical features in PMF?

Answer 30

• insidious onset in older people
• symptoms of anaemia
• massive splenomegaly- with abdominal discomfort, pain or indigestion
• hyper metabolic symptoms- weight loss, anorexia, fever and night sweats
• bleeding problems, bone pain or gout (minority)

Question 31

what are the lab findings in PMF?

Answer 31

• normochromic anaemia, but normal or increased Hb may be found
• white cell and platelet counts are high in early disease but decrease in late disease
• leucoerythroblastic blood film- tear drop poikilocytes/red cells; nucleated red cells in peripheral blood; immature granulocytes
• BM trephine biopsy- fibrotic, hypercellular
• increased megakaryocytes in BM
• high serum urate and high LDH levels
• JAK2 mutation in 50% of pts
• osteosclerosis in some patients

Question 32

what is the treatment for PMF?

Answer 32

• blood transfusions + regular folic acid therapy
• ruxolitinib
• hydroxycarbamide (hydroxyurea)
• splenectomy
• allopurinol
• allogenic SCT

Question 33

what is mastocytosis?

Question 34

what are the symptoms of mastocytosis?

Question 35

how is mastocytosis treated?