Brainscape's Knowledge GenomeTM

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


See full index

PathY5 > CML and myeloproliferative disorders > Flashcards

CML and myeloproliferative disorders Flashcards

1
Q

What are the types of polycythaemia?

A

Relative (low plasma) non malignant

True (high RBC)

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

What are the types of true polycythaemia?

A

Secondary (reactive)

Primary Polycythaemia Vera (MPD - neoplasm)

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

What causes relative polycythaemia?

A

Alcohol
Obesity
Diuretics

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

How is EPO different in primary and secondary polycythaemia?

A

Primary: reduced
Secondary: raised

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

What are the causes of appropriately raised RBC (true secondary polycythaemia)?

A

High altitude
Hypoxic lung disease
Cyanotic Heart Disease
High affinity Hb

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

What are the causes of inappropriately raised RBC (true secondary polycythaemia)?

A

Inappropriate

Renal disease (cysts, tumours inflammation)
uterine myoma

Other tumours (liver, lung)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the types of myeloid malignancies?

A

Acute myeloid leukaemia (Blasts >20%)
Myelodysplasia (blasts 5-19%)
Myeloproliferative disorders
Chronic myeloid leukaemia

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

What are the myeloproliferative disorders?

A 
(Ph (philadelphia chromosome) negative)
Essential thrombocythaemia (megakaryocyte)

Polycythemia vera (erythroid)

Primary myelofibrosis

(Ph positive)
Chronic myeloid leukaemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the types of lymphoid malignancies?

A

(precursor cells) Acute lymphoblastic leukaemia

(Mature cell malignancy)
CLL

Multiple myeloma

Lymphoma/ Hodgkins and Non Hodgkins lymphoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the cells created by normal haematopoeisis?

A 
T cell (from Pre T) 
B cell (from Pre B)
RBCs (from BFU-E)
Megakaryocyte (from Meg-CFC)
Granulocytes (from GM-CFC)
Monocytes (from GM-CFC)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What processes are disrupted by mutation?

A 
Cellular proliferation (Type 1)
Impair/ block cellular differentiation (Type 2)
Prolong cell survival (Anti apoptosis)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the mechanisms of mutation?

A 
DNA point mutations
Chromosomal translocations (Creation of novel fusion gene, disruption of proto oncogenes)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What do tyrosine kinases do?

A

Transmit cell growth signals from surface receptors to nucleus

Activated by transferring phosphate groups to self and downstream proteins

Normally held tightly in inactive state

Promote cell growth do not block maturation

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

What diseases occur as a result of mutationally activated TK in RBCs, PLTs and granulocytes?

A

Expansion increase in monoclonal mature/end cells

Red cells; polycythaemia

Platelets; essential thrombocythaemia

Granulocytes; chronic myeloid leukaemia

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

Which gene mutations are associated with myeloproliferative disorders (MPD)?

A

JAK 2 (many MPD- all polycythaemia vera)
Calreticulin
MPL (some)

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

Who gets Polycythaemia vera?

A

Incidence: 2-3/ 100,000
Slightly more male (1.2:1)
60 yo (mean- 5% below 40y)

Incidental finding

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

How does PV present?

A

Hyperviscosity
(Headache, stroke, light headed, visual disturbance, fatigue, SOB)

Histamine release (Aquagenic pruritis, peptic ulceration)

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

What are the clinical findings of PV?

A 
Splenomegaly (79%)
Plethora
Erythromelalgia
Thrombosis
Renal vein engorgement
Gout (high RBC turnover)
Test JAK2 - JAK2 wild type

No other cause

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

What are the aims of treatment of PV?

A 
Reduce viscosity (hct <45%)
>> Venesection
>> Hydroxycarbamide (cytoreductive maintenance)

Reduce thrombosis risk
» Aspirin
» Platelets <400 x 10^9/L

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is essential thrombocythaemia (ET)?

A

Chronic MPN mainly involving megakaryocytic lineage

Sustained thrombocytosis >600x109/L

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Who gets ET?

A

Incidence 1.5 per 100000

Mean age two peaks 55 years and minor peak 30 years

Females :males equal first peak but females predominate second peak

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is the clinical presentation of ET?

A

Thrombosis (CVA, TIA, gangrene, DVT, PE)

Bleeding (Mucous M and cutaneous)

Minor headaches/ dizzy/ visual disurbance

Splenomegaly (maybe)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is the treatment for ET?

A

Aspirin (prevent VTE)

Anagrelide (inhibition of Plt- SE: palpitations, flushing)

Hydroxycarbamide (antimetabolite, mildly leukaemogenic)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What is the prognosis/ complications of ET?

A

Normal life span may not be changed in many patients.

Leukaemic transformation in about 5% after >10 years

Myelofibrosis also uncommon, unless there is fibrosis at the beginning

25
Q

What is primary myelofibrosis (PMF)?

A

A clonal myeloproliferative disease with proliferation mainly of megakaryocytes and granulocytic cells, associated with reactive bone marrow fibrosis and extramedullary haematopoieisis

26
Q

Who gets PMF?

A

Incidence 0.5-1.5 /100000

Males=females

7th decade. Less common in younger patients

Secondary to other haematological disease: progression from PV or ET

27
Q

What is the clinical presentation of PMF?

A

Incidental in 30%

  1. Blood:
    Cytopenias (anaemia/ thrombocytopenia)

Thrombocytosis

  1. Organ:
    Massive Splenomegaly [Budd Chiari]

Hepatomegaly

  1. Metabolism:
    Hypermetabolic state
    (wt loss, fatigue, SOB, night sweats, hyperuricaemia)
28
Q

What are the stages of myelofibrosis?

A

Prefibrotic

Fibrotic

29
Q

What happens in the prefibrotic stage of myelofibrosis?

A

Blood changes mild but may also be confused with ET

Hypercellular marrow

30
Q

What happens in the fibrotic stage of myelofibrosis?

A

Splenomegaly and blood changes

Dry tap
Prominent collagen fibrosis
Later Osteosclerosis

31
Q

What is the prognosis of PMF?

A

3-5 years

32
Q

What are bad prognositic signs in PMF?

A

Severe anaemia <10g/dL

Thrombocytopenia <100x109/l

Massive splenomegaly

Prognostic scoring system (DIPPS)
Score 0 – median survival 15years
Score 4-6– median survival 1.3 years

33
Q

What is the treatment of PMF?

A

Transfusions (for anaemia)

Plt transfusions (but often ineffective)

Splenectomy for symptomatic relief (but hazardous and worsens symptoms)

Cytoreductive therapy: hydroxycarbamide for thrombocytosis, may lead to worsening of anaemia

Ruxolotinib JAK2 inhibitor (high prognostic score)

Bone marrow transplant in young patients may be curative (experimental)

34
Q

Who gets CML?

A

M:F 1.4:1

40-60 years

35
Q

What does CML present with?

A
  • Weight loss, lethargy, night sweats
  • Splenomegaly
  • Features of anaemia
  • Bruising/bleeding
  • Gout
36
Q

What would you find in the history and exam with CML?

A

History
Lethargy/ hypermetabolism/ thrombotic event : monocular blindness CVA

Exam
Massive splenomegaly +/- hepatomegaly

37
Q

What would you find on blood investigations with CML?

A

FBC
Hb and platelets well preserved or raised
Massive leucocytosis 50-200x109/L

Blood film
Neutrophils and some myelocytes (not blasts if chronic phase)
Basophilia

38
Q

What are the lab features of CML?

A

Mature myeloid cells
Bi phasic peak Neutrophils and myelocytes
No excess (<5%) myeloblasts

Platelet count raised/upper normal
Basophils
Leucocytosis between 50 – 500x109/l

39
Q

What is the chronic phase of CML?

A

-approximately 80% of patients with CML are diagnosed in the chronic-phase

-can last from a few months to about 4-5 years
-nearly 80% of patients with CML will progress from the
chronic-phase to the accelerated-phase
-5% or fewer of the cells in the blood and bone marrow
are blast cells

Median 5–6 years stabilisation

40
Q

What is the accelerated phase of CML?

A

10-19% of the cells in the blood and bone marrow are blast cells
Median duration6–12 months

41
Q

What is the blast crisis in CML?

A

≥20% of the cells in the blood and bone marrow are blast cells
Median survival3–6 months

42
Q

What makes the Philadelphia chromosome?

A

t(9;22) - BCR-ABL (210 kD protein made)

Fusion oncoprotein with tyrosine kinase activity

43
Q

How do you monitor disease and response to therapy in CML?

A

FBC and measure leucocyte count
Cytogenetics and detection of Philadelphia chromosome
RT-PCR of BCR-ABL fusion transcript which can be quantified by RQ-PCR to determine response to therapy

44
Q

How do leukaemia markers correlate with levels of ‘residual’ leukaemia in the body?

A

Disease detectable:
BCR-ABL / ABL (%)

Disease undetectable:
negative / [no. of ABL transcripts]

45
Q

Summarise monitoring for CML response to therapy?

A

FBC
Restored to normal FBC

Cytogenetics
Reduction in percentage of Ph metaphases

RT-PCR
Log reduction in BCR-ABL : ABL ratio

46
Q

What are the types of response to therapy in CML?

A

Haematological response
Complete Haematological Response WBC<10x109/l

Cytogenetic response (on 20 metaphases)
Partial 1-35% Philadelphia positive 
Complete 0% Ph positive

Molecular ( reduction in % BCR-ABL transcripts)
BCR-ABL transcripts reduce 100% > 10% > 1% > 0.1%
Major Molecular response (MMR) <0.1% (3 log reduction)

47
Q

What therapy can be used in CML?

A

Oral active ABL kinase Inhibitor (TKIs)
1st Generation Imatinib (Glivec)
2nd generation Dasatanib, and Nilotinib

48
Q

Pathogenesis is an activated Tyrosine Kinase cABL in CML

A

Pathogenesis is an activated Tyrosine Kinase cABL in CML

49
Q

Why are the ‘ib’s not a panacea?

A 
Poor response:
> Failure to achieve CCyR 
> Loss of MMR
> Acquiring abl point mutations leading to resistance
> Evolution to blast crisis

Non compliance

Side effects; fluid retention pleural effusions

50
Q

What is the clinical course of CML using TKIs?

A

Average 95% 5 year survival
Annual mortality 2%

Commence on oral TKI 1st generation- Monitor response FBC, Cytogenetics, RQ-PCR

CCyR at 12mo 97% FFP at 6 years (Fail to achieve CCyr 80%)

51
Q

What happens if there is a loss or failure to respond to TKIs in CML?

A

Switch to 2nd Generation TKI

Consider allogeneic Stem cell transplant

52
Q

What is the difference between Type 1,2 and anti apoptotic mutations?

A

T1: Mutations in Tyrosine Kinase genes cause excess proliferation (no effect on differentiation)
• BCR-ABL1 CML
• JAK2 MPD

T2: Mutations in nuclear transcription factors may block differentiation. If present along with a proliferation mutation can cause acute leukaemia
• PML-RARA in acute promyelocytic
leukaemia

Mutations in apoptosis genes may occur in lymphomas
• BCL2 and Follicular lymphoma

53
Q

What type of treatment is used for CML?

A

Imatinib/ TyrK inhibitor

54
Q

What causes hepatosplenomegaly with no lymphadenopathy?

A

PMF

CML

55
Q

What would you find on blood film in PMF?

A

Leucoerythroblastic picture
Tear drop poikilocytes
Giant platelets
Circulating megakaryocytes

56
Q

What would you find in BM in PMF?

A

Dry Tap

57
Q

What would you find in a trephine in PMF?

A

> Increased reticulin or collagen fibrosis
Prominent megakaryocyte hyperplasia and clustering with abnormalities
New bone formation

58
Q

What happens in the liver and spleen in PMF?

A

Extramedullary haemopoiesis in spleen and liver

PathY5 (98 decks)

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