Myeloid Malignancies

Question 1

What are the clinical signs of acute myeloid leukaemia?

Answer 1

Triad of bone marrow

• Anaemia (associated symptoms)
• Thrombocytopenic bleeding (Purpura and mucosal membrane bleeding)
• Infection because of neutropenia (can have high white counts due to blasts but low neutrophils)

Question 2

What is the WHO definition of acute myeloid leukaemia?

Answer 2

WHO definition of AML is more than 20% of marrow cells being blast cells

Question 3

What investigations should be done in acute myeloid leukaemia?

Answer 3

Blood count and blood film
Bone marrow aspirate/ trephine
Cytogenetics (Karyotype) from leukaemic blasts
Immunophenotyping of leukaemic blasts
CSF examination if symptoms (always in children)
Targeted molecular genetics for associated acquired gene mutations
e.g. FLT3, NPM1, IDH 1 & 2
Increasing use of extended NGS myeloid gene panels in AML

Question 4

What is the definition of remission in acute myeloid leukaemia?

Answer 4

In remission, the blood count is normal and the blast count is less than 5% of the marrow count

Question 5

What is the management of acute myeloid leukaemia?

Answer 5

Supportive care
Anti-leukaemic Chemotherapy –to achieve & consolidate remission
-Daunorubicin & cytosine arabinoside (DA)
-High dose cytosine arabinoside
-Gemtuzumab Ozogamicin
-CPX-351
Allogeneic stem cell transplantation –transplant-gives new immune system that recognises leukaemia as foreign and kills it
Targeted treatment
-Midostaurin in FLT3 mutated AML

Question 6

What is acute promyelocytic leukaemia?

Answer 6

The differentiation is further down the line, very high chance of them bleeding to death, esp ICH, DIC

Question 7

What is the presentation of chronic myeloid leukaemia?

Answer 7

Anaemia
Splenomegaly, often massive-due to infiltration
Weight loss
Hyperleukostasis - Fundal haemorrhage and venous congestion, altered consciousness, respiratory failure.
Gout

Question 8

What are the laboratory features in chronic myeloid leukaemia?

Answer 8

High white count and platelets
Slight anaemic
Maturation is maintained, all different cells are raised
No lymphocytes being raised as not lymphoid malignancy
In CNL it looks like the bone marrow has been moved into the blood
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 9

What are the investigations that should be done in chronic myeloid leukaemia?

Answer 9

FBC
Complete metabolic profile
Peripheral blood smear
Bone marrow biopsy
Cytogenetics
Quantitative reverse transcription PCR (qRT-PCR) including breakpoint analysis
Fluorescent in situ hybridisation (FISH)
Presence of Philadelphia chromosome and /or molecular demonstration of the BCR-ABL transcript confirms diagnosis.

Question 10

What is the management of chronic myeloid leukaemia?

Answer 10

Tyrosine Kinase Inhibitors
-Imatinib (Glivec)
-Dasatinib (Sprycel)
-Nilotinib  (Tasigna)
- Busitinib
-Ponatinib
(Direct inhibitors of BCR-ABL : First line in all patients nowadays)
Allogeneic Transplantation

Question 11

What are three myeloproliferative neoplasms?

Answer 11

Polycythaemia Vera
Essential Thrombocythaemia
Idiopathic Myelofibrosis

Question 12

What is polycythaemia vera?

Answer 12

Polycythaemia vera is a Philadelphia chromosome-negative myeloproliferative neoplasm. It is a clonal haematopoietic disorder characterised clinically by erythrocytosis and often thrombocytosis, leukocytosis, and splenomegaly. It is associated with an increased risk of thrombosis and haemorrhage. It may progress to spent phase (post-PV myelofibrosis) and, uncommonly, to a devastating acute leukaemia. Diagnosis is strongly associated with the presence of the JAK2 V617F somatic mutation.
Chronic hypoxia can cause a secondary polycythaemia

Question 13

What is the presentation of polycythaemia vera?

Answer 13

Features of thrombosis
Features of haemorrhage
Asymptomatic
Headache
Generalised weakness/fatigue
Pruritus
Erythromelalgia
Redness of fingers, palms, toes, heels, face
Splenomegaly
Itch
Age over 40

Question 14

What investigations should be done in polycythaemia vera?

Answer 14

Haemoglobin-elevated
Haematocrit-raised
White blood cell (WBC) count-elevated
Platelet count-elevated
Mean corpuscular volume (MCV)-low, iron deficient
Liver function tests (LFTs)-normal
JAK2 gene mutation screen
Uric acid-raised

Question 15

What is the management of polycythaemia vera?

Answer 15

Venesection to keep the haematocrit below 0.45
Aspirin
Hydroxycarbamide (HC)/Alpha Interferon
Ruxolitinib(JAK2 inhibitor) in HC failures with systemic symptoms

Question 16

What is essential thrombocythaemia?

Answer 16

A chronic myeloproliferative disorder associated with sustained dysregulated megakaryocyte proliferation, increasing the number of circulating platelets. It is associated with thrombosis and bleeding.

Question 17

What are the mutations seen in essential thrombocythaemia?

Answer 17

50% positive for JAK2V617F mutation

25% positive for calreticulin (CALR) mutation

Question 18

What is the presentation of essential thrombocythaemia?

Answer 18

Erythromelalgia-burning pain and dusky congestion of the extremities, increases with exposure to heat and improves with cold.
Splenomegaly
Arterial and venous thrombosis
Bleeding
Livedo reticularis-purplish mottled discoloration of the skin, usually on the legs
Age 50 to 70 years
Female sex
No symptoms
Headache
Dizziness, lightheadedness, and paraesthesias
Syncope and seizures
Transient visual disturbances
Hepatosplenomegaly
Priapism-persistent and painful erection
Gout

Question 19

What investigations should be done in essential thrombocythaemia?

Answer 19

FBC with peripheral smear-thrombocytosis, large platelets

Iron panel-low serum ferritin level diagnoses iron deficiency

Question 20

What is the management of essential thrombocythaemia?

Answer 20

Treated with aspirin and hydroxycarbamide or anagrelide

Can progress to myelofibrosis or AML