Myeloid Malignancy Flashcards
1
Q
What is the difference between AML and myeloproliferative disorders?
A
AML is proliferation without differentiation, but also get myeloproliferative disorders where differentiation has occurred:
2
Q
What are the main groups of myeloid malignancy?
A
- Acute myeloid leukaemia (AML)
- Chronic myeloid leukaemia (CML)
- Myelodysplastic syndromes (MDS)
- Pre-leukaemia conditions
- Myeloproliferative neoplasm (MPN)
3
Q
What does AML stand for?
A
- Acute myeloid leukaemia (AML)
4
Q
What does CML stand for?
A
- Chronic myeloid leukaemia (CML)
5
Q
What does MDS stand for?
A
- Myelodysplastic syndromes (MDS)
- Pre-leukaemia conditions
6
Q
What does MPN stand for?
A
- Myeloproliferative neoplasm (MPN)
7
Q
What is the difference between acute and chronic myeloid leukaemia?
A
Old terms, basically describes how long patients survive with illness:
8
Q
Compare and contrast acute and chronic myeloid leukaemia for:
- ability to differentiate
- bone marrow failure
- prognosis
- curability
A
9
Q
Describe the pathophysiology of AML?
A
- Acute myeloid leukaemia replaces bone marrow leading to bone marrow failure
- Proliferation without differentiation
10
Q
Describe the clinical features of AML?
A
- Bone marrow failure (triad)
- Anaemia
- Thrombocytopenic bleeding (purpura and mucosal membrane bleeding)
- Infection because of neutropenia (predominantly bacterial and fungal)
11
Q
What forms the triad of bone marrow failure symptoms?
A
- Anaemia
- Thrombocytopenic bleeding (purpura and mucosal membrane bleeding)
- Infection because of neutropenia (predominantly bacterial and fungal)
12
Q
What pattern of bleeding occurs in bone marrow failure?
A
Thrombocytopenic bleeding (purpura and mucosal membrane bleeding)
13
Q
What investigations should be done for AML?
A
- Blood count and blood film
- Bone marrow aspirate
- Blasts > 20% of marrow cells in acute leukaemia
- Cytogenetics (Karyotype) from leukaemic blasts
- Prognostic info
- Immunophenotyping of leukaemic blasts
- Prognostic info – to identify as myeloid or lymphoid
- CSF examination if symptoms
- Prognostic info
- Targeted molecular genetics for associated acquired gene mutations
- Looks at individual genes for mutations, such as FLT3 and NPM1
14
Q
What genetic mutations are potentially important for AML?
A
- Targeted molecular genetics for associated acquired gene mutations
- Looks at individual genes for mutations, such as FLT3 and NPM1
15
Q
What % of cells in bone marrow do blasts form in AML?
A
- Bone marrow aspirate
- Blasts > 20% of marrow cells in acute leukaemia
16
Q
Describe the treatment for AML?
A
- Supportive care
- Anti-leukaemic chemotherapy
- Remission induction (1-2 cycles)
- Classified as normal blood counts and <5% blasts
- Consolidation (1-3 cycles)
- Maintenance
- Remission induction (1-2 cycles)
17
Q
At what % of blasts in bone marrow is considered to be remission in AML?
A
- Classified as normal blood counts and <5% blasts
18
Q
Describe the pathophysiology of CML?
A
- Proliferation with differentiation
19
Q
Describe the clinical features of CML?
A
- Anaemia
- Splenomegaly
- Often massive
- Weight loss
- Hyperleukostasis
- Fundal haemorrhage and venous congestion, altered consciousness, respiratory failure
- Gout
20
Q
What are symptoms of hyperleukostasis?
A
- Fundal haemorrhage and venous congestion, altered consciousness, respiratory failure
21
Q
What investigations should be done for CML?
A
- Blood count
- Massively raised WBC
- Various different cells raised
- Raised platelets
- Immature cells raised
- Massively raised WBC
- Blood film
- All stages of white cell differentiation with increase basophils
- Bone marrow aspirate
- Hypercellular
- Cytogenetics (Karytype)
- Philadelphia chromosome in blood cells and bone marrow (chromosome 9 and 22 translocation), putting the BCR-ABL genes together and causing the disease
22
Q
What is seen in the FBC for CML?
A
- Massively raised WBC
- Various different cells raised
- Raised platelets
- Immature cells raised
23
Q
What is seen in the blood film for CML?
A
- All stages of white cell differentiation with increase basophils
24
Q
What is seen in the bone marrow aspirate for CML?
A
- Hypercellular
25
What is often seen in cytogenetics for CML?
* Philadelphia chromosome in blood cells and bone marrow (chromosome 9 and 22 translocation), putting the BCR-ABL genes together and causing the disease
26
Describe the treatment of CML?
* Tyrosine kinase inhibitors (TKIs) of BCR-ABL – first line
* Drugs
* Imatinib
* Dasatinib
* Nilotinib
* Bostinib
* Ponatinib
* Allogeneic transplantation
* Only in TKI failure
27
What are some examples of myeloproliferative neoplasms?
* Polycythaemia vera (PV)
* Essential thrombocythaemia (ET)
* Idiopathic myelofibrosis
* Often advanced stages of PV and ET
28
What does PV stand for?
Polycythaemia vera
29
What does ET stand for?
Essential thrombocythaemia
30
Describe the pathophysiology of MPN?
* Mutation of gene
* JAK2 gene (95% of PV)
* Normally indicates red cells to proliferate when signalling protein erythropoietin has binded, but with mutation does not need signalling protein
* CALR mutation (25% of ET)
31
What genes are often involved in MPN?
* JAK2 gene (95% of PV)
* Normally indicates red cells to proliferate when signalling protein erythropoietin has binded, but with mutation does not need signalling protein
* CALR mutation (25% of ET)
32
Describe the clinical features of PV?
* Headaches
* Itch
* Vascular occlusion
* Thrombosis
* TIA, stroke
* Splenomegaly
33
What investigations should be done for PV?
* Blood count
* **Raised haemoglobin concentration and haematocrit**
* Raised white cell and platelet count
* Not as high as in leukaemia
* Raised uric acid
* True increase in red cell mass when blood volume is measured
34
What is seen in the FBC for PV?
* **Raised haemoglobin concentration and haematocrit**
* Raised white cell and platelet count
* Not as high as in leukaemia
* Raised uric acid
* True increase in red cell mass when blood volume is measured
35
Describe the treatment for PV?
* Venesection
* To keep haematocrit below 0.45 (45%)
* Aspirin
* Cytoreduction
* Hydroxcarbamide or alpha interferon
* To bring platelet count and WCC down
* Ruxolitinib (JAK2 inhibitor)
* In HC failures with systemic symptoms
36
What are possible complications of PV?
Complications:
* Stroke and other arterial or venous thrombosis
* Bone marrow failure from development of secondary myelofibrosis
* Transformation to AML
37
Describe the aetiology of ET?
* JAK2 mutation 50%
* CALR mutation 25%
38
Describe the presentation of ET?
* Symptoms of arterial and venous thrombosis
* Digital ischaemia
* Gout
* Headache
* Splenomegaly
* Mild
39
What investigations should be done for ET?
* Blood count
* **Raised platelet**
* Blood film
* Thrombocytosis with giant platelets
40
What is seen on the blood count and blood film for ET?
* Blood count
* **Raised platelet**
* Blood film
* Thrombocytosis with giant platelets
41
Describe the treatment for ET?
* Aspirin
* Hydroxycarbamide or anagrelide
42
What is a possible complication of ET?
* Can progress to myelofibrosis or AML
