Myeloproliferative disorders

Question 1

What is a myeloproliferative disorder?

Answer 1

Cancer in the bone marrow
Uncontrolled proliferation of a single type of stem cells
Cells usually remain mature and functional

Question 2

What other types of cancer can myeloproliferative syndrome develop into?

Answer 2

Acute myeloid leukaemia

Question 3

What mutations are myeloproliferative disorders associated with?

Answer 3

JAK2 -> important one
MPL
CALR

Question 4

What is ruxolitinib?

Answer 4

A JAK2 inhibitor
Used in the treatment of myeloproliferative disorders

Question 5

What are the three different types of myeloproliferative disorders?

Answer 5

Primary myelofibrosis
Polycythaemia Vera
Essential thrombocythaemia

Question 6

In primary myelofibrosis what cell line is affected and what is found in the blood?

Answer 6

Affects - Haematopoietic stem cells
Low Hb, high/loww wcc, high/low platelets

Question 7

What cell line and blood findings are abnormal in polycythaemia vera?

Answer 7

Erythroid cells
High Haemoglobin

Question 8

What cell line and blood findings are abnormal in essential thrombocythaemia?

Answer 8

Megakaryocytes
High platelets

Question 9

What is the key presentation of myeloproliferative disorders?

Answer 9

Initially asymptomatic -> non-specific symptoms: fatigue, weight loss, night sweats and fever.

Question 10

What are the signs/symptoms of underlying complications in myeloproliferative disorders?

Answer 10

Anaemia
Splenomegaly
Portal hypertension
Low platelets (bleeding/petechiae)
Raised haemoglobin
Low white blood cells (infections)
Gout (polycythaemia)

Question 11

How do you diagnosis myeloproliferative disorders?

Answer 11

Bone marrow biospy - may be dry in myelofibrosis due to scar tissue
Testing for JAK2 and other genes can be helpful.

Question 12

What is the treatment for primary myelofibrosis?

Answer 12

Mild - none, symptom management
Chmotherapy = hydroxycarbamide
Targeted therapies - JAK2 inhibitors
Allogenic stem cell transplants (potentially curative)

Question 13

What is the typical treatment for polycythaemia vera?

Answer 13

Venesection to lower Hb
Aspirin to lower risk of thrombus formation
Chemotherapy

Question 14

What is the management for essential thrombocythaemia?

Answer 14

Aspirin to lower risk of thrombus formation
Chemotherapy
Anagrelide - platelet lowering drug.

Question 15

What are the common complications of myeloproliferative disorders?

Answer 15

Myelofibrosis - bone marrow fibrosis due to cytokines - dec rbcs, wbc and platelets
Trigger haematopoesis in liver/spleen - cause hepatomegaly, splenomegaly and portal HTN

Question 16

What is seen on a blood film for myelofibrosis?

Answer 16

Teardrop shaped RBCs
Anisocytosis (varying sizes of RBCs)
Blasts (immature red and white cells)

Question 17

What is myelodysplatic syndrome?

Answer 17

Cancer caused by a mutation in the myeloid cells in the bone marrow
Causing ineffective hematopoiesis
Risk of transforming into AML.

Question 18

What is the common cellular affects of myelodysplatic syndrome?

Answer 18

Low levels of blood components from myeloid cell line
Anaemia, neutropenia, thrombocytopenia = pancytopaenia

Question 19

What are the risk factors for myelodysplastic syndrome?

Answer 19

Old age
Previous chemotherapt

Question 20

What is the presentation of myelodysplastic syndrome?

Answer 20

Asymptomatic - incidental finding on FBC
Anaemia (fatigue, pallor, SOB)
Neutropenia (frequent or severe)
Thrombocytopaenia (bleeding/petechiae)

Question 21

How should myelodysplastic syndrome be diagnosed?

Answer 21

Full blood count will be abnormal
Blood films shows blasts (immature cells)
Bone marrow biopsy confirms the diagnosis.

Question 22

What is the typical management for myelodysplastic syndrome?

Answer 22

Watchful waiting
Supportive - blood/platelet transfusions
EPO to stim rbc production
GCSF (filgrastim) stim neut production
Chemo and targeted therapies
Allogenic stem cell transplant - risky but curative