Myeloid Malignancies

Question 1

What are the 4 major myeloid malignancies?

Answer 1

AML
CML
Myelodysplastic Syndromes
Myeloproliferative Neoplasms

Question 2

How does AML work?

Answer 2

A mutation in a stem cell –> Leukaemic stem cell

Allows self-renewal of progenitor cells, proliferation & blocking of differentiation

Leads to a mass of blast cells pushing out the healthy stem cells –> Bone marrow failure

Question 3

Clinically how would you encounter a case of AML?

Answer 3

Bone Marrow Failure:

• Anaemia
• Thrombocytopenic bleeds (Purpura/petechiae & mucosal bleeds)
• Neutropenic infections (bacterial/fungal)

Question 4

How would you approach an AML patient?

Answer 4

FBC & blood film

Bone Marrow Aspirate (confirms)

Question 5

Once you have a diagnosis of leukaemia what further testing is done?

Answer 5

Cytogenetics & immunophenotyping of blasts (allows determining myeloblasts vs lymphoblasts as well as subclasses)

CSF exam if they have CNS symptoms

Targeted molecular genetics - Assesses ass mutations that tell us about prognosis and treatment e.g. FLT3

Question 6

How do we manage someone with AML?

Answer 6

• Supportive Care
• Anti-leukemic Chemo
• Allogenic Stem Cell Transplant

Targeted Treatment e.g. Midostaurin in FLT3 AML
Monoclonal Antibodies

Question 7

How can you treat Low risk Acute Promyelocytic Leukaemia?

Answer 7

Can do it “chemo-free” with:

ATRA (all-trans retinoic acid) & ATO (Arsenic Trioxide)

Question 8

How would a patient with CML present?

Answer 8

Anaemia
Splenomegaly
Weight loss
Gout
Hyperleukostasis

Question 9

What are the presentations of hyperleukostasis?

Answer 9

Fundal Haemorrhage
Venous Congestion
Altered Congestion
Resp Failure

Question 10

How do we test for CML?

Answer 10

FBC & Blood Film (High WCC, platelets, myeloid cells & anaemia)

Bone Marrow Aspirate - Hypercellular

Philadelphia Chromosome t(9;22) found in bone marrow & blood cells

Question 11

How can you treat CML?

Answer 11

Not chemo:

• Tyrosine Kinase inhibitors e.g. Imatinib (Glivec)
• Allogenic Stem Cell Transplants (If TKI fails)

Question 12

What are myelodysplastic syndromes?

Answer 12

Acquired clonal disorders of the bone marrow that mostly affect elderly people

Question 13

How do myelodysplastic syndromes present?

Answer 13

With macrocytic anaemia & pancytopenia

It can progress to bone marrow failure & AML

Question 14

How do you treat Myelodysplastic syndromes?

Answer 14

Not curative
Treatment is supportive
Some young patients can get stem cell transplant

Question 15

What are the major types of myeloproliferative neoplasms?

Answer 15

Polycythaemic Vera (PV)
Essential Thrombocythaemia (ET)
Idiopathic Myelofibrosis (IM)

Question 16

What mutations are associated with Myeloproliferative neoplasms?

Answer 16

JAK2V617F - 95% of PV & 50% of ET

CALR - 25% of ET

Question 17

What happens in PV?

Answer 17

Excess of myeloid cells (predominantly RCs) -->
Headache
Itch
Vascular occlusion & thrombosis
Splenomegaly

Question 18

What test results would you expect in PV?

Answer 18

FBC:

• Raised Hb & haematocrit
• Raised WCC & platelets
• Raised URic Acid
• Increased RC mass

Question 19

How do you treat a case of PV?

Answer 19

Venesection (lowers haematocrit)
Aspirin

Hydroxycarbamide –> IF fails use Ruxolitinib (JAK2 inhibitor)

Question 20

When would we use Hydroxycarbamide in PV cases?

Answer 20

Only if they have additional vascular risk factors e.g. HTN or DM
OR if they’re >60

Question 21

What is Essential Thrombocythaemia?

Answer 21

A myeloproliferative neoplasm, predominantly affecting platelets

• Thrombi
• Digital Ischaemia
• Gout
• Headache
• Splenomegaly

Question 22

How do we treat ET?

Answer 22

Aspirin

Hydroxycarbamide or Anagrelide

Question 23

What’s the danger of Myeloproliferative Neoplasms?

Answer 23

They can progress to Myelofibrosis (causes bone marrow failure) or AML