Chronic Myeloproliferative Disorders

Question 1

What does proliferative mean?

Answer 1

To grow or multiple by rapidly producing new tissue, parts, cells or offspring

Question 2

Describe myeloproliferative disorders

Answer 2

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

Question 3

Is maturation depleted or preserved?

Answer 3

Preserved

Question 4

What is BCR-ABL1 +ve?

Answer 4

Chronic myeloid leukaemia

Question 5

What is BCR-ABL -ve?

Answer 5

Idiopathic myelofibrosis
Polycythaemia rubra vera
Essential thrombocytopenia

Question 6

When would you consider a myeloproliferative disorder?

Answer 6

High granulocyte count
High red cell count/Hb
High platelet count
Eosinophilia/basophilia
Splenomegaly
Thrombosis in an unusual place

Question 7

What is Chronic Myeloid Leukaemia? (CML)

Answer 7

Proliferation of myeloid cells

Granulocytes and their precursors and platelets

Question 8

What is needed to help prevent CML from being fatal?

Answer 8

Stem cell / bone marrow transplantation in the chronic phase

Question 9

What are the 3 phases of CML?

Answer 9

Chronic
Accelerated
Blast crisis

Question 10

What are clinical features of CML?

Answer 10

Asymptomatic
Splenomegaly
Hypermetabolic symptoms
Gout
Problems related to hyperleucocytosis and priapism

Question 11

What are lab features of CML?

Answer 11

Normal or reduced Hb
Leukocytosis with neutrophilia and myeloid precursors (myelocytes), eosinophilia, basophilia
thrombocytosis
Bone marow changes

Question 12

What is the chromosome, the gene and the product which causes the abnormal phosphorylation (signalling) leading to the haematological changes seen in CML?

Answer 12

Chromosome = Philadelphia chomosome (22)
Gene = BCR-ABL1
Product = Tyrosine kinase

Question 13

What can be used to treat CML?

Answer 13

Imatinib

Question 14

Describe Polycthaemia rubra vera? (PRV)

Answer 14

High haemoglobin / haematocrit accompanied by arythrocytosis (a true increase in red cell mass) but can have excessive production of other lineages

Question 15

Describe secondary polycythaemia?

Answer 15

Chronic hypoxia
Smoking
Erythropoietin-secreting tumour

Question 16

Describe pseudopolycthaemia?

Answer 16

Dehydration
Diuretic therapy
Obesity

Question 17

What are clinical features of PRV?

Answer 17

Clinical features common to MPD?
Headache
Fatigue
Itch (aquagenic puritis)

Question 18

What happens with the Philadelphia chromosome?

Answer 18

22 and 9 swap some bits of information

Translocation

Question 19

How do you investigate polycthaemia?

Answer 19

History
Examination
FBC + film
JAK2 mutation status

Question 20

Describe JAK2?

Answer 20

It’s a kinase
Mutation present in over 95% of PRV patients
Substitution results in loss of auto-inhibition
Activation of erythropoiesis in the absence of ligand

Question 21

What are some infrequent tests for polycythaemia?

Answer 21

Erythropoietin levels

Bone marrow biopsy

Question 22

What are investigations for secondary polycythaemia?

Answer 22

CXR
O2 saturations
Arterial blood gas
Drug history

Question 23

What is the treatment for PRV?

Answer 23

Vensect to haemocrit <0.45
Aspirin
Cytotoxic oral chemo (e.g. hydroxycarbamide)

Question 24

Describe ET

Answer 24

Uncontrollable production of abnormal platelets with abnormal function
Thrombosis
Can cause bleeding due to acquired von Willebrand disease

Question 25

What are clinical features of ET?

Answer 25

Common to MPD (esp. vasooclusive complications | Bleeding

Question 26

How do you diagnose ET?

Answer 26

``` Exclude reactive thrombocytosis Exclude CML Genetics: JAK2 (50%) CALR (calreticulin) MPL Bone marrow appearances ```

Question 27

How do you treat ET?

Answer 27

Anti-platelet agents (aspirin) | Cytoreductive therapy to control proliferation - hydroxycarbamide, anagrelide, interferon alpha

Question 28

What can myelofibrosis be?

Answer 28

Idiopathic Agnogenic myeloid metaplasia Post-polycythaemia or essential thrombocythaemia

Question 29

Describe idiopathic myelofibrosis?

Answer 29

``` Marrow failure Bone marrow fibrosis Extramedullary hematopoiesis Leukoerythroblastic Teardrop-shaped RBC's in peripheral blood ```

Question 30

What are clinical features of myelofibrosis?

Answer 30

Marrow failure - anaemia, bleeding, infection Splenomegaly - LUQ pain, portal hypertension Hypercatabolism

Question 31

How do you diagnose myelofibrosis?

Answer 31

Typical blood film (tear-drop shaped RBC and leucoerythroblastic) Fibrosis on trephine biopsy JAK2 or CALR mutation

Question 32

What are a leucoerythroblastic film ?

Answer 32

Reactive (sepsis) Marrow infiltration Myelofibrosis

Question 33

How do you treat myelofibrosis?

Answer 33

Supportive care (blood transfusion, antibiotics) Allogenic stem cell transplantation in select few Splenectomy JAK2 inhibitors

Question 34

What counts as abnormal platelets?

Answer 34

Infection increase Iron deficiency Malignancy Blood loss