Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

CSP > Myeloproliferative syndromes > Flashcards

Myeloproliferative syndromes Flashcards

1
Q

Chronic Myeloid Leukaemia is characterised by…?

A

Dysregulated and uncontrolled proliferation of mature and maturing granulocytic cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What translocation is associated with CML (and ALL)?

What does this cause?

A

Reciprocal translocation 9:22 (Philadelphia chromosome) –> BCR-ABL 1 fusion gene –> gene encodes tyrosine kinase (an enzyme that can transfer phosphate group from ATP to a protein = on/off switch) which becomes ‘constitutively active’ and unregulated by cytokines (i.e. it doesn’t switch off) –> uncontrolled, proliferation and cell division and inhibits DNA repair leading to genetic instability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What % of leukaemia in adults does CML make up?

A

15-20%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Incidence of CML.

A

1-2 per 100,000

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What population is CML more common in?

What is the median age?

A

More common in males, median age 50 years

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Clinical features of CML.

A
  • Many asymptomatic
  • Systemic symptoms - fatigue, night sweats, malaise, weight loss
  • Splenomegaly - early satiety, LUQ fullness/pain
  • Increased uric acid due to high cell turnover - acute gout
  • Hyper-viscosity – headache/blurred vision, fluid overload, thrombosis and haemorrhage
  • Bone pains
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What do you see on the blood film with CML?

A

Maturing granulocytes, e.g. basophils

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How is CML diagnosed?

A
  • Raised WCC (+ basophilia)
  • Blood Film
  • Bone marrow biopsy
  • Chromosome G-banding
  • FISH
  • Quantitative real time PCR – used to monitor BCR-ABL positive RNA levels during treatment every 3 months
  • For Exams – Low NAP/ LAP score
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How is CML managed? (3)

A
  • Imatinib and 2nd/3rd generation TKI’s (Dasatinib, Nilotinib)
  • Chemotherapy for refractory/ accelerated phase/blast crisis
  • Allogeneic Haematopoietic Stem Cell Transplant
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Prognosis of CML

A
  • Now excellent in era of TKIs – normal life expectancy

* Small proportion of patients are resistant to TKIs who need chemotherapy +/- Bone marrow transplant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is Primary Polycythaemia (Rubra) Vera?

A

Increased red cell volume due to a clonal malignancy of a marrow stem cell. Usually > RBCS but all 3 cell lines can be increased.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Primary Polycythaemia (Rubra) Vera is characterised by…?

A

Characterised by otherwise unexplained elevated HCT/RCM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What mutation is associated with Primary Polycythaemia (Rubra) Vera in 95% of cases?

A

JAK2 Mutation (a signaling molecule)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Epidemiology of Primary Polycythaemia (Rubra) Vera - incidence and median age.

A
  • 1-2 per 100,000

* Median age approx 60

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is Polycythaemia/Erythrocytosis?

A

Raised Hct due to increase in RBCs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How is Polycythaemia/Erythrocytosis defined in males vs females?

A

Males ->0.6 (Hb 18.5)
Females ->0.56 (Hb 16.5)
for more than 2 months.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the cause of PRIMARY true/absolute polycythaemia?

Describe the EPO level.

A

polycythaemia vera

REDUCED OR NORMAL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Causes of SECONDARY true/absolute polycythaemia. (6)

A

Hypoxia driven - high altitude, cardiopulmonary disease, defective O2 transport
Hypoxia independent - renal cysts or tumours, extrarenal tumours, exogenous EPO/drugs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Describe the EPO levels in SECONDARY true/absolute polycythaemia.

A

RAISED

20
Q

What causes apparent/relative polycythaemia?

A

Reduced plasma volume

21
Q

Clinical features of polcythaemia vera?

A

Many are asymptomatic
• Plethoric Appearance / Ruddy Cyanosis
• Splenomeglay: Early satiety, LUQ fullness/pain
• Acute gout: Increased uric acid production
• Headache / Blurred Vision (hyperviscosity)
• Post bath pruritis (aquagenic pruritis)
• Erythromelalgia
• Thrombosis: Arterial or venous
• Haemorrhage

22
Q

How is polcythaemia vera diagnosed (stage 1)?

A
  • History
  • Examination
  • Full blood count
  • Ferritin (low)
  • Renal & Liver function (to check if cysts/tumour)
  • JAK 2 mutation
23
Q

How is polcythaemia vera diagnosed (stage 2)?

A

• Serum EPO (low)
• Arterial SO2 (for secondary causes)
• Abdominal US (splenomegaly, renal tumour)
• Bone Marrow Biopsy (hypercellular, trilineage
growth (panmyelosis))
• Red Cell Mass study (Nuclear study determines if
true or relative erythrocytosis)

24
Q

How is polcythaemia vera treated? (3)

A

Venesection (HCT < 0.45)
Aspirin
Myelosuppressive Drugs e.g. hydroxycarbamide, Interferon, Busulphan

25
Q

How might polcythaemia vera be treated in the future?

A

JAK inhibitors

26
Q

What is the median survival with polcythaemia vera?

A

10 – 16 years

27
Q

What do patients with polcythaemia vera most commonly die from? (6)

A 
Cardiovascular Events
Thrombosis 
Progression to Myelofibrosis 30%
Progression to AML 5%
Haemorrhage
Non haematological malignancy
28
Q

What is Essential Thrombocythaemia?

A

Sustained increase in platelet count, because of megakaryocytic proliferation
Defined by a non-reactive thrombocythaemic state that is not accounted for by another myeloproliferative neoplasm

29
Q

What is the median age of Essential Thrombocythaemia?

Is it more common in males or females?

A

60 years

Females (2:1)

30
Q

Incidence of Essential Thrombocythaemia.

A

2 per 100,000

31
Q

Prevalence of Essential Thrombocythaemia.

A

24/100,000

32
Q

10 year survival of Essential Thrombocythaemia.

A

80-90%

33
Q

Clinical features of Essential Thrombocythaemia.

A 
Many are asympomatic
• Thrombosis (arterial and venous)
• Haemorrhage (poor platelet function)
• Erythromelalgia
• Splenomegaly : Early satiety LUQ fullness/pain
• Fatigue, Malaise , Weight loss
High plts (>450 - Persistent)
34
Q

Secondary Causes of thrombocythaemia.

A
  • Infection
  • Inflammation
  • Iron deficiency
  • Haemorrhage
  • Hyposplenism
  • Malignancy
  • Drugs – steroids
  • Other myeloid malignancy
35
Q

How is Essential Thrombocythaemia diagnosed?

A

JAK 2 mutation ~ 50%, CALR ~ 30%, MPL ~ 10% - I.E. FEWER PEOPLE HAVE MUTATIONS IN ET THAN IN PV SO NEED TO DO BONE MARROW BIOPSY (can see megakaryocytes)

36
Q

How is ET treated? (2)

A

Aspirin

Myelosuppressive Drugs e.g. hydroxycarbamide, anagrelide for higher risk patients (age >60, prev thrombosis, high WCC)

37
Q

Prognosis of ET.

A

Most enjoy N survival > 10 Years

But…risk of thrombosis, bleeding, and transformation to MF (10-20%) and AML (<5%)

38
Q

What is myelofibrosis?

A

Clonal Stem Cell malignancy
Progressive generalised reactive fibrosis of the bone marrow in assosication with haematopoeisis of the liver and spleen (myeloid metaplasia).
Fibrosis is secondary to hyperplasia of abnormal megakaryocytes stimulating fibroblasts.

39
Q

Myelofibrosis can be primary or secondary. What are the secondary causes? (2)

A

ET

PV

40
Q

What mutations are associated with myelofibrosis?

A

JAK2 Mutation in 50%, CALR 30%, MPL 10%

41
Q

What are the clinical features of myelofibrosis?

A 
Fatigue
Weight loss
Night Sweats
Raised WCC
Progressive cytopenias
Massive Splenomegaly (due to BM failure)
Extramedullary-haemopoiesis
42
Q

Describe a characteristic blood film in myelofibrosis.

A

Tear drops poikilocytes

Leucoerythroblastic = a little bit of everything in the film (e.g blasts, nucleated RBCs, tear drops etc)

43
Q

What is seen in bone marrow biopsy in myelofibrosis. (3)

A

Increased reticulin fibrosis
Streaming
Hypercellular

44
Q

How is myelofibrosis diagnosed? (4)

A
  • JAK-2 mutation in 50%, CALR Mutation in 30% (better prognosis), MPL mutation in 10%, but triple negative 10% (worst prognosis)
  • Bone marrow and blood film
  • Splenomegaly
  • Anaemia
45
Q

In myelofibrosis, which mutation carries the best prognosis and which carries the worst?

A

CALR mutation = better

Triple negative = worst

46
Q

How is myelofibrosis treated? (7)

A
  • Stratify risk (age/blast count)
  • Supportive Management – transfusion
  • Splenectomy/ Splenic irradiation
  • If high risk and fit patient - ?Allogeneic Tx candidate
  • JAK Inhibitors – Ruxolitinib – potentially disease modifying. Indicated for B Symptoms and splenomegaly
  • Hydroxycarbamide
  • Androgens/Danazol
47
Q

Prognosis of myelofibrosis inc median survival.

A

Poor overall
Median survival 1 year if high risk, > 12 years if low risk
Risk of progression to AML

CSP (20 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions