Myeloproliferative Neoplasms

Question 1

What does myeloproliferative mean?

Answer 1

Myelo = bone marrow lineage 
Proliferative = to grow or multiply by rapidly producing mew tissue

Question 2

What is a clonal haemopoietic stem cell disorder?

Answer 2

Increased production of one or more types of haemopoietic cells

Question 3

Describe CML

Answer 3

Overproduction of granulocytes

BCR-ALB 1 positive = philadelphia chromosome

Question 4

Describe essential thrombocythaemia?

Answer 4

Over-production of platelets

Question 5

Describe polycythaemia vera

Answer 5

Overproduction of red cells

Question 6

What are the different types of BCR-ABL 1 negative myeloproliferative neoplasms?

Answer 6

Primary myelofibrosis
Polycythaemia vera
Essential thrombocythemia

Question 7

When should a MPN be considered?

Answer 7

High granulocyte count
High red cell count/ Hb
High platelet count 
Eosinophilia/ basophilia 
Splenomegaly 
Thrombosis in an unusual place 
With NO reactive explanation

Question 8

What are the different phases of CML?

Answer 8

Chronic phase
Accelerated phase
Blast crisis

Question 9

What are the clinical features of CML?

Answer 9

Asymptomatic 
Splenomegaly 
Hypermetabolic symptoms 
Gout 
Misc; problems related to hyperleucocytosis, priapism

Question 10

What are the lab features of CML?

Answer 10

Normal/ decreased Hb

Leucocytosis with neutrophilia and myelocytes, eosinophila, basophilia and thrombocytosis

Question 11

What is the hallmark of CML?

Answer 11

Philadelphia chromosomee

Question 12

What is the treatment for Philadelphia chromosome positive CML?

Answer 12

Tyrosine kinase inhibitor - imatinib

Question 13

What are features common to MPN?

Answer 13

Asymptomatic
Increased cellular turnover (gout, fatigue, wt loss, sweats)
Sy/si due to splenomegaly
Marrow failure; fibrosis or leukaemia transformation; PRV and ET
Thrombosis; TIA, MI, abdo vessel, claudication, erythomelagia

Question 14

What is polycythaemia vera?

Answer 14

High Hb accompanied by erythrocytosis (a true increased in red cells mass) but can have excessive production of other lineages

Question 15

What do you NEED to distinguish PV from?

Answer 15

Secondary polycythaemia; chronic hypoxia, smoking, epo-secreting tumour
Pseudopolycythaemia; dehydration, diuretic therapy, obesity

Question 16

What are the clinical features of PV?

Answer 16

Similar to MPN
Headache, fatigue (blood viscosity raised NOT plasma viscosity)
Itch; aquagenic puritis

Question 17

What are the investigations required for PV?

Answer 17

History - investigate for secondary causes (CXR, O2, ABG, drug hx)
Exam; splenomegaly
FBC, film
JAK2 mutation

Question 18

What is the most important test for PV?

Answer 18

JAK2 mutation

Question 19

What is JAK2?

Answer 19

Kinase

Results in loss of auto-inhibition and activation of epo in the absence of a ligand

Question 20

What is now part of the initial screening in PV?

Answer 20

Mutational analysis

Question 21

What is the treatment for PV?

Answer 21

Venesect to haematocrit of <0.45
Aspirin
Cytotoxic oral chemo; hydroxycarbamide

Question 22

What is ET?

Answer 22

Uncontrolled proliferation of abnormal platelets

Platelet function ABNORMAL; thrombosis, at high levels can cause bleeding due to acquired vWF disease

Question 23

What are the clinical features of ET?

Answer 23

Common MPN, particularly vasoocclusive

Bleeding

Question 24

How is ET diagnosed?

Answer 24

Exclude reactive thrombocytosis - IMPORTANT

Exclude CML

Question 25

What are the genetics of ET?

Answer 25

JAK2 in 50-60% CALR in 25% MPL in 5% 10-20% triple neg

Question 26

What is the treatment for ET?

Answer 26

Anti-platelets; aspirin | Cytoreductive therapy to control proliferation; hydroxycarbamide, anagrelide or interferon alpha

Question 27

What can cause myelofibrosis?

Answer 27

Idiopathic | Post-polycythaemia or essential thrombocythaemia

Question 28

What are the features of idiopathic myelofibrosis?

Answer 28

``` Marrow failure; variable degrees Bone marrow fibrosis Extramedullary haematopoiesis (liver and spleen) Leukoerythroblastic film appearances Tear-drop shaped RBC in peripheral blood ```

Question 29

What are the features of marrow failure?

Answer 29

Anaemia Bleeding Infection

Question 30

What are the features of splenomegaly?

Answer 30

LUQ pain Cx; portal hypertx Gastric fullness

Question 31

What are the clinical features of myelofibrosis?

Answer 31

Marrow failure Splenomegaly Hypercatabolism

Question 32

How is MF diagnosed in the lab?

Answer 32

Typical blood film; tear drop shaped RBC and leukoerythroblsatic Dry aspirate Fibrosis on trephine biopsy

Question 33

What are causes for a leukoerythroblastic film?

Answer 33

Reactive (sepsis) Marrow infiltration Myelofibrosis

Question 34

What is a leukoerythroblastic film?

Answer 34

``` Immature cells (myelocytes and normoblasts) seen on the peripheral blood film Normoblast = nucleated RBC ```

Question 35

What is the treatment of MF?

Answer 35

Supportive care; blood transfusion, platelets, antibiotics Allogenic stem cell transplantation ??Splenectomy JAK2 inhibitors (ruxolitinib)

Question 36

What are the causes for reactive high blood coutns?

Answer 36

Reactive granulocytes; infection (pyogenic bacteria causing neutrophilia), physiological (post-surgery, steroids) Reactive thrombocytosis; infection, IDA, malignancy, blood loss Reactive polycythaemia; dehydration (pseudopolycythaemia), secondary