Myeloid Malignancy

Question 1

What are the major myeloid malignancies?

Answer 1

Acute myeloid leukaemia (AML)
Chronic myeloid leukaemia (CML)
Myelodysplastic syndromes (MDS)
Myeloproliferative neoplasms (MPN)

Question 2

What are the two subgroups of acute leukaemia?

Answer 2

Acute myeloblastic leukaemia

Acute lymphoblastic leukaemia

Question 3

What are the clinical features of acute myeloid leukaemia?

Answer 3

Short history
Bone marrow failure: triad of anaemia, thrombocytopenic bleeding (purpura and mucosal bleeding) and infection due to neutropenia (white cell count can be raised but neutrophil count low)

Question 4

What investigations should be done in acute myeloid leukaemia?

Answer 4

Blood count and blood film
Bone marrow aspirate/ trephine (Blasts > 20% of marrow cells in acute leukaemia)
Cytogenetics (Karyotype) from leukaemic blasts
Immunophenotyping of leukaemic blasts
CSF examination if symptoms
Targeted molecular genetics for associated acquired gene mutations

Question 5

How is acute myeloid leukaemia treated?

Answer 5

Supportive care
Anti-leukaemic chemotherapy (daunorubicin and cytosine arabinoside, high dose cytosine arabinoside, gemtuzumab ozogamicin, CPX-351)
Allogeneic stem cell transplantation- high risk, high gain strategy. Give patient new immune system that will recognise leukaemia as foreign and kill it
All-trans retinoic acid and arsenic trioxide in low risk acute promyelocytic leukaemia
Targeted treatment

Question 6

When is somebody considered to be in remission from acute myeloid leukaemia?

Answer 6

When there is a normal blood count + blast count <5% of the marrow count

Question 7

What is the pathological cause of chronic myeloid leukaemia?

Answer 7

A mutation in the stem cell that leads to proliferation in the myeloid lineage but there is differentiation present

Question 8

What are the characteristics of chronic myeloid leukaemia?

Answer 8

Anaemia
 Splenomegaly, often massive
 Weight loss
 Hyperleukostasis - Fundal haemorrhage and venous congestion, altered consciousness, respiratory failure. Medical emergency 
Gout- due to hypermetabolic state
No bone marrow failure

Question 9

What investigations should be done in chronic myeloid leukaemia?

Answer 9

High WCC ( can be very high)
High platelet count
Anaemia
Blood film shows all stages of white cell differentiation with increased basophils
Bone marrow is hypercellular
Bone marrow and blood cells contain the Philadelphia chromosome - t(9;22)

Question 10

What is the genetic cause of chronic myeloid leukaemia?

Answer 10

Philadelphia chromosome- small chromosome 22 due to Translocation between chromosome 22 and chromosome 9. BCR-ABL oncogene on chromosome 22 causes CML

Question 11

What is the treatment of chronic myeloid leukaemia?

Answer 11

Direct inhibitors of BCR-ABL- first line treatment in all patients
Tyrosine kinase inhibitors (TKI)- imatinib, dasatinib, nilotinib, busitinib, ponatinib
Allogenic transplantation- only in TKI failure

Question 12

What are the different myeloproliferative neoplasms?

Answer 12

Polycythaemia Vera (PV)
Essential Thrombocythaemia (ET)
Idiopathic Myelofibrosis

Question 13

What is the pathological cause of myeloproliferative neoplasms?

Answer 13

Stem cell disorders resulting in proliferation of red cells and platelets. Other lineages also increased

Question 14

What are the genetic causes of myeloproliferative neoplasms?

Answer 14

Mutation in PV is JAK2 V617F mutation in 95% of cases. Same mutation causes 50% of ET and myelofibrosis. CALR mutation causes 25% of ET.

Question 15

What are the clinical features of polcythaemia vera?

Answer 15

Headaches
Itch
Vascular occlusion or thrombosis
TIA or stroke
Splenomegaly

Question 16

What are the laboratory features of polcythaemia vera?

Answer 16

A raised haemoglobin concentration and haematocrit.
A tendency to also have a raised white cell count and platelet count
A raised uric acid
A true increase in red cell mass when the blood volume is measured

Question 17

What is the haematocrit?

Answer 17

The percentage of blood made up of red cells (usually ~45%)

Question 18

How is polycythaemia vera treated?

Answer 18

Venesection (blood letting) to keep haematocrit below 0.45
Aspirin
Hydroxcarbamide (HC)/alpha interferon for white cell suppression
Ruxolitinib (JAK2 inhibitor) in failure of other treatment. Reduces symptoms but doesn’t prolong life

Question 19

What are the possible complications of polycythaemia vera?

Answer 19

Stroke and other arterial or venous thromboses if poorly controlled
Bone marrow failure from the development of secondary myelofibrosis
Transformation to AML

Question 20

What is essential thrombocythemia?

Answer 20

A myeloproliferative disease with the predominant feature of raised platelet count but similar features to PV

Question 21

What is the genetic cause of essential thrombocythaemia?

Answer 21

50% of cases are positive for JAK2V617F mutation and 25% positive for calreticulin (CALR) mutation

Question 22

What are the symptoms of essential thrombocythaemia?

Answer 22

Symptoms of arterial and venous thromboses
Digital ischaemia
Gout
Headache 
Mild splenomegaly

Question 23

How is essential thrombocythemia treated?

Answer 23

Aspirin and hydroxycarbamide or anagrelide

Question 24

What are the possible complications of essential thrombocythemia?

Answer 24

Can progress to myelofibrosis or acute myeloid leukaemia