Myeloproliferative Neoplasms (MPN)

Question 1

What are MPNs?

Answer 1

There are 3 types of MPN all if which involve proliferation of myeloid cells. It is debated whether or not they are actually cancers. They are best though of as very slow growing cancers which can progress into AML. CML used to be classed as a MPN but no longer is as it bears different genetic markers i.e. BCR-ABL

Question 2

What are most MPNs treated with?

Answer 2

Often treated with hydroxycarbamide

Question 3

What is myelofibrosis?

Answer 3

Hyperplasia of the stem cells which produce platelet derived growth factor and cytokines. This leads to intense bone marrow fibrosis and marrow failure, so haematopoiesis takes place in the spleen and liver resulting in hepatosplenomegaly. This can transform into leukaemia

Question 4

What are the signs and symptoms of myelofibrosis?

Answer 4

Bone marrow failure leading to pancytopenia

Hypermetabolic symptoms such as night sweats, fever and weight loss.

Hepatosplenomegaly due to extramedullary haemopoiesis. This also results in pooling of blood in the spleen enhancing the anaemia, also abdominal discomfort

Question 5

How should you investigate someone you suspected of having myelofibrosis?

Answer 5

Bone marrow biopsy and aspiration with film showing leucoerythroblastic cells
(nucleated red cells), poikilocytes and the marrow trephine shows a streaming effect as a result of the fibrosis
FBC showing pancytopenia (although may get a leucocytosis)
Genetic analysis looking for Jak 2 and CalR

Question 6

How is myelofibrosis managed?

Answer 6

Supportive care
Folic acid supplements
Blood transfusions
Dexamethasone

Only curative treatment is allogenic stem cell transplantation

Splenectomy may be considered if it is causes issues such as anaemia

Question 7

What is essential Thrombocythaemia?

Answer 7

Clonal proliferation of megakaryocytes leading to persistently raised platelets.

Question 8

What are the clinical features of essential Thrombocythaemia?

Answer 8

Thrombus 
Bleeding if platelets dysfunctional 
Headaches
Chest pain
Pruritis 

50% have Jak 2 mutation, 25% have CalR

Question 9

How is essential Thrombocythaemia managed?

Answer 9

High risk patients Hydroxycarbamide (note increases MCV)

Otherwise aspirin

Question 10

What can cause a reactive thrombocytosis?

Answer 10

Infection 
Chronic bleeding 
Solid cancers 
Iron deficiency 
Splenectomy 
Inflammatory disorders

Question 11

What is polycythaemia rubra vera?

Answer 11

Uncontrolled production of red cells in the bone marrow despite erythropoietin production being switched off. There will be an increase in all 3 cell lines in the marrow. Can transform into leukaemia or myelofibrosis.

Question 12

How does polycythaemia rubra vera present and which marker is found in all cases?

Answer 12

Thrombosis
Neurological symptoms such as headache, drowsiness, transient visual disturbances
Pruritis especially after being in warm water
Gout due to purine metabolism
Hepatosplenomegaly

100% have the Jak2 mutation

Question 13

How is polcythaemia rubra vera managed?

Answer 13

Venesetion

Hydroxycarbamide (note increases MCV)

Question 14

What other differentials should be considered alongside polycythaemia rubra vera?

Answer 14

Primary causes are from the bone e.g. MPN
Secondary causes include any chronic cyanotic disease such as: smoking, obstructive sleep apnoea and cyanotic heart disorders.
If none of these fit, then it may be a pseudo polycythaemia due to reduced plasma volume.

Question 15

What investigations should be completed in someone with polcythaemia?

Answer 15

Investigations

Must rule out primary causes such as MPN. Do this by checking EPO levels and cytogenetics for Jak2.