Myeloid Malignancies

Question 1

Myeloid malignancies arise from what cells?

Answer 1

• Red cells
• Platelets
• Granulocytes
• Monocytes

Question 2

Give examples of myeloid malignancies.

Answer 2

• Acute Myeloid Leukaemia (AML)
• Chronic Myeloid Leukaemia (CML)
• Myelodysplastic Syndromes (MDS)
• Myeloproliferative Neoplasms (MPN)

Question 3

Acute vs chronic myeloid leukaemia

Do leukaemic cells differentiate?

Answer 3

Acute - Do not differentiate

Chronic - Retain ability to differentiate

Question 4

Acute vs chronic myeloid leukaemia

Bone marrow

Answer 4

Acute - Bone marrow failure

Chronic - Proliferation without bone marrow failure

Question 5

Acute vs chronic myeloid leukaemia

Survival

Answer 5

Acute - Rapidly fatal if untreated

Chronic - Survival for a few years historically

Question 6

Acute vs chronic myeloid leukaemia

Treatment

Answer 6

Acute- Potentially curable

Chronic - Long term survival/ possible cures with modern therapy

Question 7

What are the sub-groups of acute leukaemia?

Answer 7

• Acute Myeloid Leukaemia (AML)
• Acute Lymphoblastic Leukaemia (ALL)

Question 8

What are the clinical features of AML?

Answer 8

Bone marrow failure

• Anaemia (SOB, angina, fatigued)
• Thrombocytopenic bleeding (Purpura and mucosal membrane bleeding)
• Infection because of neutropenia (predominantly bacterial and fungal)

Question 9

What are the essential investigations in AML?

Answer 9

• Blood count and blood film (leukaemic blasts)
• 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 (e.g. FLT3, NPM1, IDH 1 & 2)
• Increasing use of NGS (next generation sequencing) myeloid gene panels in AML

Question 10

How is AML treated?

Answer 10

• Supportive care
• Anti-leukaemic chemotherapy (to achieve and consolidate remission) (remission= blast count less than 5%, bloods normal)
• Allogeneic stem cell transplantation –to consolidate remission/potential cure
• All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) in low risk Acute Promyelocytic Leukaemia: ‘Chemo-free’ (high cure rate ~ 90%)
• Targeted treatment (e.g Midostaurin in FLT3 mutated AML)

Question 11

What anti-leukemic chemotherapy is used in treatment of AML?

Answer 11

Daunorubicin & cytosine arabinoside (DA)

Question 12

What new developments have been made in the treatment of AML?

Answer 12

• Targeted antibodies: (Gemtuzumab Ozogamicin anti-CD33 with Calicheomycin (Mylotarg) )
• Targeted small molecules (Midostaurin, Tyrosine Kinase Inhibitor including inhibiting FLT3)
• New delivery systems (CPX -351)

Question 13

How does CML present?

Answer 13

• Anaemia
• Splenomegaly, often massive
• Weight loss
• Hyperleukocytosis: Fundal haemorrhage and venous congestion, altered consciousness, respiratory failure
• Gout

Question 14

What are the laboratory features of CML?

Answer 14

• 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 15

What is the Philadelphia chromosome translocation?

Answer 15

t(9;22)

Question 16

What is the treatment for CML?

Answer 16

• Tyrosin kinase inhibitors
  
  • Imatinib (Glivec)
  • Dasatinib (Sprycel)
    
    • Direct inhibitors of BCR-ABL: first line in all patients nowadays
• Allogenic transplantation (few, only in TKI failure)

Question 17

What are myelodysplastic syndromes?

Answer 17

• Acquired clonal disorders of the bone marrow that are commonly seen in old age
• They are pre-leukemic

Question 18

How do myelodysplastic syndromes present?

Answer 18

Macrocytic anaemia and pancytopenia

Question 19

What is the outcome of myelodysplastic syndromes?

Answer 19

Fatal as a result of progression to bone marrow failure or AML

Question 20

What is the treatment for myelodysplastic syndromes?

Answer 20

Supportive or a stem cell transplantation for the few young patients

Question 21

What are the clinical features of Polycythemia vera?

Answer 21

• Headaches
• Itch
• Vascular occlusion
• Thrombosis
• TIA, stroke
• Splenomegaly

Question 22

What are the laboratory features of Polycythemia vera?

Answer 22

• 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 23

What is a typical blood film of Polycythemia vera ?

Answer 23

Microcytosis with large and abnormal platelets

Question 24

What is the treatment for Polycythemia vera?

Answer 24

• Venesection to keep the haematocrit below 0.45 - men and 0.43 - women
• Aspirin
• ? Hydroxcarbamide (HC)
• ? Ruxolitinib(JAK2 inhibitor) in HC failures with systemic symptoms

Question 25

What is the natural history of Polycythemia vera?

Answer 25

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

Question 26

What is Essential thrombocythaemia?

Answer 26

A myeloproliferative disease with predominant feature of raised platelet count

Question 27

How does Essential thrombocythaemia present?

Answer 27

• Symptoms of arterial and venous thrombosis
• Digital ischaemia
• Gout
• Headache
• Mild splenomegaly

Question 28

How is Essential thrombocythaemia treated?

Answer 28

• Aspirin
• Hydroxycarbamide/ anagrelide

Question 29

What can Essential thrombocythaemia progress to?

Answer 29

Mylefibrosis or AML

Question 30

Give examples of myeloproliferative neoplasms

Answer 30

• Polycythemia vera
• Essential thrombocythaemia
• Idiopathic myelofibrosis

Question 31

What is remission in acute myeloid leukaemia?

Answer 31

remission = blast count less than 5%, bloods normal