Myeloproliferative Disorders

Question 1

What is a myeloproliferative disorder?

Answer 1

These conditions occur due to uncontrolled proliferation of a single type of stem cell. They are considered a type of bone marrow cancer.

Question 2

What are the main 3 myeloproliferative disorders?

Answer 2

1. Primary myelofibrosis
2. Polycthemia vera
3. Essential thrombocythaemia

Question 3

What is primary myelofibrosis?

Answer 3

It is the result of proliferation of the haematopoietic stem cells

Question 4

What is polycythaemia vera?

Answer 4

It is the result of proliferation of the eythroid cell line

Question 5

What is essential thrombocythaemia?

Answer 5

It is the result of proliferation of the megakaryocytic cell line

Question 6

What different proliferating cell lines cause disease?

Answer 6

Proliferating cell line and disease

Haematopoietic stem cell - primary myelofibrosis

Erythroid cells - Polycythaemia vera

Megakaryocyte - Essential thrombocythaemia

Question 7

Myeloproliferative disorders have the potential to progress and transform into AML, T/F?

Answer 7

T

Question 8

What gene mutations are myeloproliferative disorders associated with?

Answer 8

JAK2
MPL
CALR

Question 9

How can the JAK2 gene mutation be helpful in the treatment of myeloproliferative disorders?

Answer 9

It can be the target of JAK2 inhibitors such as ruxolitinib

Question 10

What is myelofibrosis?

Answer 10

Myelofibrosis can be the result of primary myelofibrosis, polycythaemia vera or essential thrombocythaemia.

Myelofibrosis is where the proliferation of the cell line leads to fibrosis of the bone marrow. The bone marrow is replaced by scar tissue. This is in response to cytokines that are released from the proliferating cells.

Question 11

What cytokine in particular is associated with myelofibrosis?

Answer 11

Fibroblast growth factor

Question 12

What can fibrosis of the bone marrow lead to in myelofibrosis?

Answer 12

The fibrosis of the bone marrow can affect the production of blood cells and lead to anaemia and low white blood cells (leukopenia).

Question 13

What happens to the production of RBCs when the bone marrow is replaced with scar tissue in meylofibrosis?

Answer 13

Production of RBCs starts to happen in other places such as the liver and the spleen. - known as extramedullary haematopoiesis and can lead to hepatomegaly and splenomegaly. -> portal hypotension and can lead to spinal cord compression.

Question 14

What is the presentation of myeloproliferative disorders?

Answer 14

Initially asymptomatic 
Then they can present systemic symptoms: 
- Fatigue 
- Weight loss 
- Night sweats 
- Fever

Question 15

What underlying complications may be seen in myeloproliferative disorders?

Answer 15

1. Anaemia (except in polycythaemia)
2. Splenomegaly (abdominal pain)
3. Portal hypertension (ascites, varices and abdominal pain)
4. Low platelets (bleeding and petechiae)
5. Thrombosis is common in polycythaemia and thrombocythaemia
6. Raised red blood cells (thrombosis and red face)
7. Low white blood cells (infections)

Question 16

What would you find on the full blood count in polycythaemia vera?

Answer 16

Raised haemoglobin (more than 185g/l in men or 165g/l in women)

Question 17

What would you find on the full blood count in primary thrombocythaemia?

Answer 17

Raised platelet count (more than 600 x 10^9/l)

Question 18

What would you find on a FBC with myelofibrosis?

Answer 18

Myelofibrosis (due to primary MF or secondary to PV or ET) can give variable findings:

• Anaemia
• Leukocytosis or leukopenia (high or low white cell counts)
• Thrombocytosis or thrombocytopenia (high or low platelet counts)

Question 19

What would you expect to see on a blood film in myelofibrosis?

Answer 19

A blood film in myelofibrosis can show teardrop-shaped RBCs, varying sizes of red blood cells (poikilocytosis) and immature red and white cells (blasts).

Question 20

How is a diagnosis of myeloproliferative disease made?

Answer 20

Bone marrow biopsy is the test of choice to establish a diagnosis. Bone marrow aspiration is usually “dry” as the bone marrow has turned to scar tissue.

Testing for the JAK2, MPL and CALR genes can help guide management.

Question 21

What is the management of primary myelofibrosis?

Answer 21

Patients with mild disease with minimal symptoms might be monitored and not actively treated.

Allogeneic stem cell transplantation is potentially curative but carries risks.

Chemotherapy can help control the disease, improve symptoms and slow progression but is not curative on its own.

Supportive management of the anaemia, splenomegaly and portal hypertension.

Question 22

What is the management of polycythaemia vera?

Answer 22

Venesection can be used to keep the haemoglobin in the normal range. This is the first line treatment.

Aspirin can be used to reduce the risk of developing blood clots (thrombus formation).

Chemotherapy can be used to control the disease

Question 23

What is the management of essential thrombocythaemia?

Answer 23

Aspirin can be used to reduce the risk of developing blood clots (thrombus formation).

Chemotherapy can be used to control the disease.