4.3 Chronic Myeloproliferative Disorders

Question 1

What is the term for too much red, ahite and platelets?

Answer 1

red: Polycythaemia
White: Leukocytosis
Platelets: Thombocytosis

Question 2

What is the term for too little red, white and platelets

Answer 2

Red: Anaemia
White: Leucopenia
Platelets: Thrombocytopenia

Question 3

Where do the genetic changes in CML occur?

Answer 3

Pluripotent stem cell

Question 4

What is the common genetic abnormality in CML?

Answer 4

Translocation between chromosomes 9 (ABL) and 22 (BCR) leading to an increase in the ABL tyrosine kinase which is important in signal transduction and cell growth

Question 5

What are the clinical features of CML?

Answer 5

Fatigue, weight loss, night sweats, splenomegaly, anaemia

Question 6

What is used for the diagnosis of CML?

Answer 6

Changes on peripheral blood and BM biopsy

BCR-ABL translocation (cytogenetis)

Question 7

What are the three phases of CML?

Answer 7

Chronic
Accelerated
Blast

Question 8

What is the treatment of CML?

Answer 8

Tyrosine kinase inhibitor - Imatinib

Reduces the progression to accelerated phase or blast phase however some patients will develop mutations that reduce the effectiveness - new generation tyrosine inhibitors being used

Question 9

What is polycythaemia vera?

Answer 9

Primary polycythaemia where there is an increase in RBC production independent of EPO

Question 10

What are the clinical features of Polycythaemia vera?

Answer 10

Increased risk of arterial and venous thrombosis
Microcirculatory disorders - headaches, cisual disturbances, dizziness, erythromelagia
Hypertension
Plethora
Splenomegaly

Question 11

What is the genetic mutation of polycythaemia vera?

Answer 11

Gain of function in Janus 2 kinase (JAK-2) which is the gene that encodes the tyrosine kinase a downstream regulator of EPO making cells hypersensitive to EPO

Question 12

In which disorders will you see JAK2 mutations?

Answer 12

Polycythaemia vera
Essential thrombocytopenia
Primary idiopathic myelofibrosis

Question 13

What is the diagnosis of polycythaemia vera?

Answer 13

Serum EPO suppressed
Identification of JAK2 mutation
Bone marrow biopsy: panmyelosis

Question 14

What is the treatment of polycythaemia vera?

Answer 14

Venesection: reduces the blood volume and brings down the hematocrit levels; in patients with polycythemia vera, this reduces the risk of blood clots

Low dose aspirin
JAK2 inhibitors being developed

Question 15

What is essential thrombocythaemia?

Answer 15

Chronic myeloproliferative neoplasm affecting the megakaryocytic lineage

Question 16

What is the diagnosis of thrombocythaemia?

Answer 16

Sustained platelet count >450
Bone marrow: proliferation of megakaryocytes (no increase in erythropoiesis or granulopoiesis)
Doesn’t meet criteria for other myeloproliferative disease
JAK2 V617F nutation positive

Question 17

What is the clinical presentation of thrombocythaemia?

Answer 17

Most aymptomatic but can show thrombosis or haemorrhage

Question 18

What is the treatment of thrombocythaemia?

Answer 18

Hydroxyurea (affects all cell lines)
Anagrelide (megakaryocyte line - more side effects)
Low dose aspirin if high risk of vascular events

Question 19

What is primary myelofibrosis?

Answer 19

proliferation of megakaryocytes and granulocytes in the bone marrow

In developed disease this is associated with reactive deposition of fibrosis connective tissue and extramedullary haematopoiesis

Question 20

What are the clinical features of primary myelofibrosis?

Answer 20

30% asymptomatic - incidental splenomegaly or FBC abnormalaties
Can mimic essential thrombocytopenia
90% splenomegaly
50% hepatomegaly
Fatigue, dyspnoea, weight loss, night sweats, bleeding

Question 21

What is the diagnosis of primary myelofibrosis?

Answer 21

Leukoerythroblastic on blood film
Bone marrow biopsy - proliferative, fibrotic phases
May have JAK2 or anothe rmutation

Question 22

What is the clinical course of primary myelofibrosis?

Answer 22

As it progresses cytopenias develop 
Usually become transfusion dependent 
Ongoing splenic enlargement 
3-7 year survival if diagnosed in fibrotic phase 
5-30% transformation into AML

Question 23

What is Nilotinib?

Answer 23

Tyrosine kinase inhibitor used for imatinib resistant CML

Question 24

What is Ponatinib?

Answer 24

Kinase inhibitor targets at ABL-BCR used for CML and Ph+ ALL

Effective for CML resistant to imatinib

Question 25

What is Ruxolitinib?

Answer 25

JAK 1 and 2 inhibitor for myelofibrosis