Myeloproliferative Neoplasms

Question 1

what are myeloproliferative neoplasms (MPNs)?

Answer 1

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

Question 2

what do MPNs result in?

Answer 2

increased production of mature, differentiated cells

Question 3

what are the two groups of MPNs?

Answer 3

BCR-ABL1 negative diseases

BCR-ABL1 positive diseases

Question 4

name three BCR-ABL 1 MPNs?

Answer 4

polcythaemia vera
primary myelofibrosis
essential thrombocythaemia

Question 5

name a BCR-ABL 1 positive MPN

Answer 5

chronic myeloid leukaemia

Question 6

what happens in CML?

Answer 6

the proliferation of myeloid cells

Question 7

how does CML present?

Answer 7

can be asymptomatic
splenomegaly
gout
hypermetabolic symptoms

Question 8

what features are seen on the blood count in CML?

Answer 8

normal or reduced HB
leucocytosis with neutrophilia, eosinophilia and basophilia
thrombocytosis

Question 9

what bone marrow change is seen in CML?

Answer 9

increased cellularity

Question 10

what is the genetic hallmark of CML?

Answer 10

the philadelphia chromosome

Question 11

what does the philadelphia chromosome result in?

Answer 11

formation of a new gene - BCR-ABL1

results in production of a tyrosine kinase with causes abnormal phosphorylation

Question 12

what drugs can be given for CML?

Answer 12

tyrosine kinase inhibitors

Question 13

name a tyrosine kinase inhibitor

Answer 13

imatinib

Question 14

what are the features common to MPNs?

Answer 14

may be asymptomatic 
gout 
fatigue 
weight loss 
sweats 
splenomegaly 
thrombosis

Question 15

what is erythromelalgia?

Answer 15

redness and pain in the hands and feet due to microvascular occlusion

Question 16

what blood count changes are seen in polycythemia vera (PV)?

Answer 16

high Hb/haematocrit accompanied by erythrocytosis

Question 17

what can cause secondary polcythaemia?

Answer 17

chronic hypoxia

Question 18

what can causes pseudopolycythaemia?

Answer 18

dehydration
diuretic therapy
obesity

Question 19

how does PV present?

Answer 19

headache
fatigue
aquagenic pruritus

Question 20

what genetic mutation is seen in PV?

Answer 20

JAK2 mutations - seen in 95% of patients

Question 21

what is the main aim of treatment for PV?

Answer 21

reduce thrombosis risk

Question 22

how is PV managed?

Answer 22

venesect to haematocrit <0.45
aspirin
cytotoxic oral chemotherapy

Question 23

what chemotherapy drug can be given for PV?

Answer 23

hydroxycarbamide

Question 24

what happens in essential thrombocythaemia (ET)?

Answer 24

overproduction of platelets

Question 25

what is there a risk of in ET?

Answer 25

thrombosis

Question 26

what genetic mutations can be seen in ET?

Answer 26

JAK2 CALR MPL some patients are "triple negative" and have no mutations

Question 27

what is the characteristic bone marrow appearance in ET?

Answer 27

increased amounts of abnormal looking megakaryocytes

Question 28

how is ET managed?

Answer 28

aspirin | cytoreductive therapy to control proliferation

Question 29

what drugs can be involved in the cytoreductive therapy in ET?

Answer 29

hydroxycarbamide anagrelide interferon alpha

Question 30

how does primary myelofibrosis (PMF) present?

Answer 30

marrow failure splenomegaly hypercatabolism

Question 31

what is seen on the blood film in PMF?

Answer 31

tear drop shaped RBC | leucoerythroblastic changes

Question 32

what does leucoerythroblastic mean?

Answer 32

the presence of neutrophil and red cell precursors

Question 33

what mutations can be seen in PMF?

Answer 33

JAK2 CALR MPL

Question 34

how is PMF managed?

Answer 34

supportive care JAK2 inhibitors allogenic stem cell transplant in very few patients

Question 35

name a JAK2 inhibitor

Answer 35

ruxolitinib