Myeloproliferative neoplasms

Question 1

What does myeloproliferative mean?

Answer 1

Myelo = bone marrow lineage(s)

Proliferative = to grow or multiply

Question 2

What are myeloproliferative neoplasms?

Answer 2

A clonal haemopoietic stem cell disorder with an increased production of one or more haemopoietic cells

Question 3

How does myeloproliferative neoplasms contrast to acute leukaemia?

Answer 3

Maturation is relatively preserved in myeloproliferative neoplasms

Question 4

What compartment of cells are / are not included in myeloproliferative neoplasms?

Answer 4

Haemopoietic stem cells - erythrocytes, platelets, macrophages, granulocytes

Lymphoid cells are not included

Question 5

Name a common subtype of
BCR-ABL1 positive myeloproliferative neoplasms?

Answer 5

Chronic myeloid leukaemia

Question 6

Name three subtypes of BCR-ABL 1 negative myeloproliferative neoplasms?

Answer 6

Essential thrombocythaemia

Polycythaemia Vera

Primary myelofibrosis

Question 7

What is chronic myeloid leukaemia characterised by?

Answer 7

Philadelphia chromosome

Question 8

When should myeloproliferative neoplasms be considered in a patient?

Answer 8

A high granulocyte count
A high haemoglobin
A high platelet count
Eosinophilia / basophilia

Splenomegaly
Thrombosis in an unusual place

Key - there is NO REACTIVE EXPLANATION for these figures

Question 9

What are the classic features of myeloproliferative neoplasms?

Answer 9

Generally asymptomatic

Increased cellular turnover - gout, fatigue, weight loss, sweats

Splenomegaly signs and symptoms

Marrow failure

Thrombosis

Question 10

What is chronic myeloid leukaemia?

Answer 10

A clonal haemopoietic proliferative disorder

Question 11

What is a ‘blast crisis’ in chronic myeloid leukaemia?

Answer 11

A stage of disease reminiscent of acute leukaemia but with a maturation defect

Question 12

What are the clinical features of chronic myeloid leukaemia?

Answer 12

Many patients asymptomatic

Increased cellular turnover

Splenomegaly

Question 13

What are the blood count changes seen in chronic myeloid leukaemia?

Answer 13

Normal or low haemoglobin

Leucocytosis with neutrophilia and myeloid precursors

Eosinophilia, basophilia

Question 14

What does the genetic mutation of the Philadelphia chromosome in chronic myeloid leukaemia result in?

Answer 14

A new chimeric gene called
BCR-ABL 1

Question 15

What is BCR-ABL1?

Answer 15

A tyrosine kinase which causes abnormal phosphorylation

Question 16

What can be used to treat chronic myeloid leukaemia?

Answer 16

Tyrosine kinase inhibitors
e.g. Imatinib

Question 17

What is polycythaemia vera?

Answer 17

A high haemoglobin / haematocrit accompanied by a true increase in red cell mass

Can have excessive production of other lineages

Question 18

What is pseudopolycythaemia?

Answer 18

A false reading of increased red cell mass due to dehydration, reduction in plasma volume, obesity etc

Question 19

What is secondary polycythaemia?

Answer 19

Polycythaemia caused by chronic hypoxia, smoking, erythropoietin-secreting tumours etc

Question 20

What are the clinical features of polycythaemia vera?

Answer 20

Features common to MPN

Headache, fatigue

Itch - Aquagenic Puritis

Question 21

Which gene is commonly mutated in patients with primary polycythaemia vera?

Answer 21

JAK2 gene

Question 22

What is one of the front-line tests for the diagnosis of polycythaemia vera?

Answer 22

Mutational analysis

Specifically JAK2 analysis

Question 23

What is the treatment for polycythaemia vera?

Answer 23

Venesection - haematocrit <0.45

Aspirin

Cytotoxic oral chemotherapy

JAK inhibitor e.g. Ruxolitinib

Question 24

What is essential thrombocythaemia?

Answer 24

Uncontrolled production of abnormal platelets

Question 25

What are the clinical features of essential thrombocythaemia?

Answer 25

Clinical features common to MPN Vaso-occlusive complications Bleeding - unpredictable

Question 26

What should always be excluded when investigating for essential thrombocythaemia?

Answer 26

Reactive thrombocytosis

Question 27

How is chronic myeloid leukaemia ruled out when investigating for suspected essential thrombocythaemia?

Answer 27

BCR-ABL1 testing

Question 28

What genetic mutations are commonly seen in essential thrombocythemia patients?

Answer 28

JAK2 mutations in 50-60% CALR mutations in ~25%

Question 29

What treatment is given for essential thrombocythaemia?

Answer 29

Anti-platelet agents - Aspirin Cytoreductive therapy to control proliferation

Question 30

How is idiopathic myelofibrosis ideintified?

Answer 30

An abnormal proliferation of marrow fibroblasts causing bone marrow fibrosis Extramedullary haematopoiesis

Question 31

How is idiopathic myelofibrosis identified on a blood film?

Answer 31

Leucoerythroblastic film appearances Teardrop-shaped RBCs in peripheral blood

Question 32

What are the clinical features of myelofibrosis?

Answer 32

Marrow failure - anaemia, bleeding Splenomegaly - LUQ pain Hypercatabolism

Question 33

What are the 3 common causes of a leucoerythroblastic blood film?

Answer 33

Reactive (sepsis) - most common Marrow infiltration Myelofibrosis

Question 34

How should myelofibrosis be managed?

Answer 34

Supportive care - transfusions Allogenic stem cell transplantation can be done in select patients

Question 35

Which medications can be given to myelofibrosis patients?

Answer 35

JAK inhibitors They improve spleen size and constitutional symptoms

Question 36

What is the most common cause of high blood cell counts?

Answer 36

Reactive causes Infection, dehydration etc.