Myeloid Malignancy

Question 1

What is acute myeloid leukaemia?

Answer 1

Haematological malignancy resulting in the overproduction of immature myeloid cells/myeloid progenitors, building up and replacing bone marrow, causing bone marrow failure

Question 2

What age group is acute myeloud leukemia more common?

Answer 2

Peak age of onset 70 years

Question 3

How common is AML?

Answer 3

The more common form of acute leukaemia in adults

Question 4

What is the prognosis of AML?

Answer 4

Long term survival 50%

Question 5

Give risk factors for AML

Answer 5

Down Syndrome

Radiotherapy

Chemotherapy

Secondary transformation of a myeloproliferative disorder

Associated conditions

• Chronic myeloid leukaemia
• Myelodysplasia
• Myelofibrosis
• Polycythaemia rubra vera

Question 6

How does AML present?

Answer 6

Anaemia

• Dyspnoea
• Fatigue
• Malaise/weakness
• Pallor

Thrombocytopenic bleeding

• Purpura and muscle membrane bleeding

Infection

• Prolonged neutropenia

Bone pain and tenderness

Gum swelling

Lymphadenopathy

Splenomegaly

Question 7

When does gum swelling occur in AML?

Answer 7

Only in monocytic variety, due to monocytic infiltration

Question 8

What is an ecchymosis?

Answer 8

Large bruise

Question 9

What investigations are used in AML diagnosis?

Answer 9

Bone marrow biopsy

• Auer rods
• High numbers of blast cells

FBC

• Anaemia
• Increased WCC
• Thrombocytopenia

Blood film

• Leukaemic myeloblasts within blood

Question 10

What biopsy sign is seen in AML?

Answer 10

Blasts >20% of marrow cells

Question 11

How is AML managed?

Answer 11

Supportive

• Anti-fungal and antibiotic prophylaxis
• Blood transfusions

Chemotherapy

Allogenic stem cell transplantation

Question 12

What classifications is used for AML?

Answer 12

French-American-British (FAB)

Question 13

What is acute promyelocytic leukaemia M3?

Answer 13

Type of AML associated with t(15;17) and the fusion of PML and RAR-alpha genes. It presents younger and is associated with

• Auer rods (seen with myeloperoxidase stain)
• DIC or thrombocytopenia at presentation
• Good prognosis

Question 14

Who is a allogenic stem cell transplant usually from and why?

Answer 14

Usually from a sibling, their immune system recognises the leukemic cells as an antigen

Question 15

Give complications of AML

Answer 15

Relapse

Severe bleeding and infection

CNS infiltration

DIC

Question 16

What are the poor prognostic features of AML?

Answer 16

Over 60 years

Over 20% blasts after first course of chemo

Cytogenetics

• Deletions of chromosome 5 or 7

Question 17

What is chronic myeloid leukaemia?

Answer 17

Malignancy of granulocytes leading to increased production of myeloid precursors, with their differentiation ability still intact

Question 18

What chromosome is associated with CML?

Answer 18

Philadelphia chromosome

(Philadelphia cheese makes lunch)

Question 19

What is the Philadelphia chromosome?

Answer 19

Reciprocal translocation of chromosome 9 and 22, causing the BCR/ABL fusion gene

Question 20

What activity is associated with the Philadelphia chromosome?

Answer 20

Uncontrolled tyrosine kinase activity

Question 21

What age group is CML more common in?

Answer 21

Occurs in middle aged and elderly

Question 22

How does CML present?

Answer 22

Anaemia

Massive splenomegaly due to build up of myeloid cells

Weight loss

Gout

Sweating

Bleeding

Bruising

Petechiae

Hyperleukostasis

Question 23

What is Hyperleukostasis?

Answer 23

Significantly increased blast cells, causing

• Fundal haemorrhage and venous congestion
• Altered consciousness
• Respiratory failure

Question 24

What investigations are used in CML diagnosis?

Answer 24

Bone marrow biopsy

Philadelphia chromosome

FBC

• Increased WCC
• Low lymphocytes but high neutrophils
• Thrombocytosis
• Anaemia

Blood Film

• Granulocytes at different stages of maturation/myeloblasts and granulocytosis

Decreased leukocyte alkaline phosphatase

Question 25

How is CML managed?

Answer 25

Supportive * Blood transfusions * Antibiotics Tyrosine Kinase Inhibitors * Imatinib Interferon alpha Allogenic Transplant in TKI failures

Question 26

Give an example of a tyrosine kinase inhibitor

Answer 26

Imatinib

Question 27

Name the myeloproliferative disorders

Answer 27

Essential thrombocytosis Polycythaemia rubra vera Myelofibrosis

Question 28

What are the features of essential thrombocytosis?

Answer 28

Platelet count \> 600 \* 109/l Both thrombosis (venous or arterial) and haemorrhage can be seen Characteristic symptom is a burning sensation in the hands JAK2 mutation is found in around 50% of patients

Question 29

How is essential thrombocytosis managed?

Answer 29

Hydroxyurea (hydroxycarbamide) to reduce platelet count interferon alpha is also used in younger patients Low-dose aspirin may be used to reduce the thrombotic risk

Question 30

What is polycythaemia vera?

Answer 30

Myeloproliferative disorder caused by clonal proliferation of a marrow stem cell leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets

Question 31

What are the features of polycythaemia vera?

Answer 31

Hyperviscosity Pruritus, typically after a hot bath Splenomegaly Haemorrhage/stroke, secondary to abnormal platelet function Plethoric appearance HTN Headaches, dizzy spells and tinnitus

Question 32

What investigations are used in polycythaemia vera?

Answer 32

FBC * Increased RBC * Increased haematocrit * Normal EPO Low ESR JAK2

Question 33

How is polycythaemia vera managed?

Answer 33

Aspirin Venesection hydroxyurea, causes slight increased risk of secondary leukaemia Phosphorus-32 therapy

Question 34

What investigations are used in myelofibrosis?

Answer 34

Blood film * Tear drop poikilocytes FBC * Anaemia * Thrombocytopenia and leucopenia in progressive disease