Chronic Myeloproliferative Disorders

Question 1

Define chronic myeloproliferative disorders

Answer 1

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

In contrast to acute leukaemia maturation is preserved

Question 2

when would you consider a MPD?

Answer 2

High Granulocyte count
				
High Red cell count / haemoglobin
				
High Platelet count
				
Eosinophilia/basophilia

Splenomegaly

Thrombosis in an unusual place

Question 3

What are the different sub sets of chronic myeloid leukaemia?

Answer 3

BCR-ABL1 NEGATIVE

Essential Thrombocythaemia (over production of platelets)

Polycythaemia Rubra Vera
(over production of red cells)

Idiopathic Myelofibrosis

BCR-ABL1 POSITIVE

Chronic Myeloid Leukaemia
(over production of granulocytes)
Philadelphia Chromosome

Question 4

What is the progression of Chronic Myeloid Leukaemia?

Answer 4

chronic phase with intact maturation 3-5 years, followed by ‘blast crisis’ reminiscent of acute leukaemia with maturation defect (fatal unless BMT an option)

Question 5

clinical features of CML

Answer 5

Asymptomatic

Splenomegaly

Hypermetabolic symptoms

Gout

Misc: Problems related to hyperleucocytosis problems, Priapism

Question 6

what is the genetic hallmark of CML

Answer 6

Philadelphia chromosome- A reciprocal translocation between the long arms of chromosomes 9 and 22

Question 7

what does BRC-ABL gene code for

Answer 7

tyrosine kinase. Causes defects in signalling

Question 8

what should polycythaemia rubra vera be distinguished from?

Answer 8

secondary polycythaemia (chronic hypoxia, smoking, erythropoietin-secreting tumour etc)

pseudopolycythaemia (eg dehydration, diuretic therapy,

Question 9

what mutation is found in 95% of PRV?

Answer 9

JAK2

Question 10

PRV treatment

Answer 10

Vensect to haematocrit

Question 11

how would you diagnose essential thrombosythaemia?

Answer 11

Exclude reactive thrombocytosis IMPORTANT!!
(Blood loss, inflammation, malignancy, iron deficiency)

Exclude CML

Genetics: 	JAK2 mutations (in 50%)
		CALR (Calreticulin) in those without mutant JAK2 	MPL mutation

Characteristic bone marrow appearances

Question 12

ET treatment

Answer 12

None
Low-risk cases (age, absence of thrombosis)

Anti-platelet agents
Aspirin

Cytoreductive therapy to control proliferation
hydroxycarbamide, anagralide, interferon alpha

Question 13

what are the clinical features of myelofibrosis?

Answer 13

marrow failure
anaemia, bleeding, infection

splenomegaly
LUQ abdominal pain
Complications including portal hypertension

hypercatabolism

Question 14

what is the lab diagnosis of MF?

Answer 14

typical blood film (tear-drop shaped RBC and leucoerythroblastic)

dry aspirate

fibrosis on trephine biopsy

JAK2 or CALR mutation in a proportion

Question 15

what are the causes of a Leucoerythroblastic film

Answer 15

reactive sepsis
marrow infiltrate
mf

Question 16

what is the treatment of MF?

Answer 16

Supportive care (blood transfusion, platelets, antibiotics)

Allogeneic stem cell transplantation in a select few

Splenectomy (CONTROVERSIAL)

JAK2 inhibitors (improve spleen size, QoL, ?survival)