Myeloproliferative Neoplasms

Question 1

What are myeloproliferative neoplasms?

Answer 1

Clonal haemopoietic stem cell disorders with an increased production of one or more types of haemopoietic cells

Question 2

Is maturation preserved in myeloproliferative neoplasms?

Answer 2

Yes = it is relatively preserved

Question 3

What does microscopy of myeloproliferative neoplasm show?

Answer 3

Hypercellular with a variety of cells at different stages of development

Question 4

How are myeloproliferative neoplasms classified?

Answer 4

Broadly split using BCR-ABL1 = can be positive or negative

Question 5

What is an example of a BCR-ABL1 positive myeloproliferative neoplasm?

Answer 5

Chronic myeloid leukaemia = overproduction of granulocytes

Question 6

What are some examples of BCR-ABL1 negative myeloproliferative neoplasms?

Answer 6

Primary myelofibrosis
Polycythaemia vera = red cell overproduction
Essential thrombocythaemia = platelet overproduction

Question 7

When would you consider myeloproliferative neoplasm as a diagnosis?

Answer 7

High granulocyte count +/- high red cell count +/- high platelet count +/- eosinophilia/basophilia +/- splenomegaly and thrombosis in unusual places

Question 8

What must be excluded before diagnosing myeloproliferative neoplasm?

Answer 8

Reactive causes of blood abnormalities

Question 9

What is chronic myeloid leukaemia?

Answer 9

Proliferation of myeloid cells = granulocytes and their precursors, platelets

Question 10

What is the course of chronic myeloid leukaemia?

Answer 10

Chronic phase = intact maturation, 3-5 years

Blast crisis = lack of progenitors (view on blood film)

Question 11

What is the prognosis of chronic myeloid leukaemia?

Answer 11

Fatal without stem cell or bone marrow transplant in chronic stage

Question 12

What are the features of chronic myeloid leukaemia?

Answer 12

Asymptomatic, splenomegaly, hypermetabolic syndrome, gout, priaprism, problems related to hyperleucocytosis

Question 13

What lab results would you expect in a patient with chronic myeloid leukaemia?

Answer 13

Normal or reduced Hb, leucocytosis with neutrophilia and myelocytes, eosinophilia, basophilia, thrombocytosis

Question 14

What does bone marrow biopsy of chronic myeloid leukaemia show?

Answer 14

Hypercellularity

Question 15

What is the hallmark of chronic myeloid leukaemia?

Answer 15

Philadelphia chromosome = due to transolcation between chromosomes 9 and 22

Question 16

What does the Philadelphia chromosome cause?

Answer 16

Chimeric BCR-ABL1 gene = tyrosine kinase is produced which leads to haematological changes due to abnormal phosphorylation

Question 17

What treatment targets the Philadelphia chromosome to treat chronic myeloid leukaemia?

Answer 17

Tyrosine kinase inhibitors = imatinib

Question 18

What patient age group is most affected by BCR-ABL1 negative myeloproliferative neoplasms?

Answer 18

Patients aged >65

Question 19

What are the common features of the BCR-ABL1 negative myeloproliferative neoplasms?

Answer 19

Asymptomatic, fatigue, weight loss, sweats, gout, splenomegaly, marrow failure (esp primary myelofibrosis), thrombosis, erythromelalgia

Question 20

What are the characteristics of polycythaemia vera?

Answer 20

High Hb and haematocrit accompanied by erythrocytosis = causes true increase in red cell mass

Question 21

How do you distinguish between secondary polycythaemia and pseudo-polycythaemia?

Answer 21

Using a centrifuge = shows increase in red cell mass present in polycythaemia

Question 22

What are the features of polycythaemia vera?

Answer 22

Headache, fatigue, itch (exacerbated by warm water)

Question 23

What investigations are done for polycythaemia vera?

Answer 23

FBC, blood film, JAK2 mutation analysis (present in 95%)

Question 24

What is the JAK2 mutation?

Answer 24

Mutation in kinase = results in loss of auto-inhibition and activation or erythropoiesis in absence of ligand

Question 25

How is polycythaemia vera treated?

Answer 25

Venesect to haematocrit <0.45, aspirin, cytotoxic oral chemotherapy (e.g hydroxycarbamide)

Question 26

What occurs in essential thrombocythaemia?

Answer 26

``` Uncontrolled production of abnormal platelets Abnormal platelet function = thrombosis, vWF disease at high level (>1500) causing bleeding ```

Question 27

What are the features of essential thrombocythaemia?

Answer 27

Veno-occlusive features, bleeding

Question 28

What must be excluded before essential thrombocythaemia can be diagnosed?

Answer 28

Reactive causes and chronic myeloid leukaemia

Question 29

What are the genetics associated with essential thrombocythaemia?

Answer 29

50-60% have JAK2 mutation, 25% have CALR mutation and 5% have MPL mutation 10-20% have none of these mutations

Question 30

What is the main diagnostic test for essential polycythaemia?

Answer 30

Bone marrow biopsy

Question 31

What is the treatment of essential polycythaemia?

Answer 31

Aspirin | Cytoreductive therapy = hydroxycarbamide mainly, also angrelide or INF-alpha

Question 32

What is the least common BCR-ABL1 negative myeloproliferative neoplasm?

Answer 32

Primary myelofibrosis = can be idiopathic or post-polycythaemia/essential thrombocythaemia

Question 33

What are the features of primary myelofibrosis?

Answer 33

Marrow failure, bone marrow fibrosis, extramedullary haemopoiesis (hepatosplenomegaly), anaemia, bleeding, infections, LUQ pain, hypercatabolism (e.g weight loss)

Question 34

What is the blood film appearance of primary myelofibrosis?

Answer 34

Leukoerythroblastic blood film with teardrop shaped red cells in the peripheral blood

Question 35

How is primary myelofibrosis diagnosed?

Answer 35

Blood film = characteristic appearance Bone marrow aspirate = expect dry tap Trephine biopsy = shows fibrosis

Question 36

What are the genetics associated with primary myelofibrosis?

Answer 36

Most patients are JAK2 positive, followed by CALR then MPL mutations 10% have none of these mutations

Question 37

What is a leucoerythroblastic film appearance?

Answer 37

Presence of both red cell and neutrophil precursors in blood = can also be caused by sepsis and marrow infiltration

Question 38

What is the treatment of primary myelofibrosis?

Answer 38

Supportive = blood transfusion, platelets, antibiotics Allogenic stem cell transplant in select few JAK2 inhibitors = improve spleen size and symptoms Splenectomy = less common and controversial

Question 39

Are myeloproliferative neoplasms a common cause of abnormally high cell counts?

Answer 39

No = reactive causes of raised counts are more common