Myeloid Malignancy

Question 1

Features of acute myeloid leukaemia

Answer 1

Leukaemic cells do not differentiate
Bone marrow failure
Rapidly fatal if untreated
Potentially curable

Question 2

Features of chronic myeloid leukaemia

Answer 2

Leukaemic cells retain ability to differentiate
Proliferation without bone marrow failure
Survival for a few years
Long term survival/possible cures increasing with modern therapy

Question 3

Clinical features of chronic myeloid leukaemia

Answer 3

Anaemia
Splenomegaly, often massive
Weight loss
Hyperleukostasis - fundal haemorrhage and venous congestion, altered consciousness, respiratory failure
Gout
Typical blood count shows no bone marrow failure, just proliferation

Question 4

Laboratory features of CML

Answer 4

High WCC
High platelets
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

Question 5

Treatment of CML

Answer 5

Tyrosine Kinase Inhibitors

• imatinib
• dasatinib
• nilotinib
• busitinib
• ponatinib
• direct inhibitors of BCR-ABL, first line in all patients

Allogeneic transplantation - few patients, only in TKI failures

Question 6

Subgroups of acute myeloid leukaemia

Answer 6

Acute myeloblastic leukaemia

Acute lymphoblastic leukaemia

Question 7

Clinical features of acute myeloblastic leukaemia

Answer 7

Bone marrow failure

• anaemia
• thrombocytopenic bleeding (purpura and mucosal bleeding)
• infection due to neutropenia (predominantly bacterial and fungal)

Question 8

Essential investigations of acute myeloblastic leukaemia

Answer 8

Blood count and blood film
Bone marrow aspirate/trephine biopsy
Cytogenetics of leukaemic blasts - carries good prognostic information (more than 20% blasts in bone marrow = acute leukaemia)
CSF examination if symptoms indicate
Molecular genetics for associated acquired gene mutations e.g. FLT3, NPM1, IDH 1 and 2

Question 9

Treatment of AML

Answer 9

Supportive care

Anti-Leukaemic chemotherapy

• produces complete and absolute neutropenia for 2-3 weeks
• among most intense chemotherapy regimes
• supportive care very important

Stem cell transplantation

• allogeneic
• selective patients
• effect not dependent on chemotherapy

All-Trans Retinoic Acid in APL

Question 10

What newly developed drugs are used in AML treatment?

Answer 10

Targeted antibodies

• gentuzumab ozogamicin anti-CD33 with calcicheomycin
• midostaurin; TKI, including inhibiting FLT3

Question 11

Features of myelodysplastic syndromes

Answer 11

Acquired clonal disorders of the bone marrow
Commonly seen in old age
Present as macrocytic anaemia and pancytopenia
Pre-Leukaemia
Fatal as a result of progression to bone marrow failure or AML

Question 12

Treatment of myelodysplastic syndrome

Answer 12

Supportive

Stem cell transplantation for the few young patients

Question 13

Presentation of myelodysplastic syndromes

Answer 13

Macrocytic anaemia and pancytopenia

Question 14

How many people with myelodysplastic syndromes will go on to develop AML?

Answer 14

1/3rd

Question 15

What are the myeloproliferative disorders?

Answer 15

Polycythaemia vera
Essential thrombocythaemia
Idiopathic myelofibrosis

Question 16

In what percentage of polycythaemia vera and essential thrombocythaemia is JAK2V617F mutation found?

Answer 16

95% of PV

50% of ET

Question 17

In what percentage of essential thrombocythaemia is CALR mutation found?

Answer 17

25%

Question 18

Clinical features of polycythaemia vera

Answer 18

Headache
Pruritis
Vascular occlusion
Thrombosis
TIA, stroke 
Splenomegaly

Question 19

Laboratory features of PV

Answer 19

Raised haemoglobin concentration and haematocrit
Tendency to also have raised WCC and platelet count
Raised uric acid
True increase in red cell mass when blood volume is measured

Question 20

Treatment of PV

Answer 20

Venesection to keep haematocrit below 0.45
Aspirin
Hydroxycarbamide

Question 21

Natural history of PV

Answer 21

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

Question 22

Features of essential thrombocythaemia

Answer 22

Myeloproliferative disease with predominant features of platelet count
Symptoms of arterial and venous thromboses, digital ischaemia and gout
Mild splenomegaly

Question 23

Treatment of ET

Answer 23

Aspirin

Hydroxyurea

Question 24

What can ET progress to?

Answer 24

Myelofibrosis or AML