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Haematology > Cancers of Myeloid Cell Origin > Flashcards

Cancers of Myeloid Cell Origin Flashcards

1
Q

What is CML

A

Proliferation and differentiation of leukaemic stem cells
Increased end cells / monocytosis
Most commonly neutrophil affected
Present without bone marrow failure as no blocked differentiation
Proliferation of bone marrow that makes mature end-cells so lots of granulocytes

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2
Q

What is prognosis

A

Survival for a few years
Long term now achievable with modern therapy - attacking Philadelphia chromosome
CLL a bit behind

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3
Q

What is +Ve in majority of CML and what is important

A

Philadelphia chromosome t(9:22)(q34:q11)
Translocation 9-22
Give rise to mutant BCL-ABL on chromosome creating tyrosine kinase
Leads to uncontrolled cell cycling
Genetically unique as only require this one mutation to get disease rather than multiple hits
More +Ve prognosis in CML.
Dx by FISH / molecular testing

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4
Q

How does CML present

A

Insidious
WCC increasing = leucocytosis
Classicaly neutrophils + basophils
Can sometimes get thrombocytosis
Anaemia chronic disease - lethargy
Slight bone marrow failure (no neutropenia or thrombocytopenia)
Massive splenomegaly
B symptoms - Weight loss /fever / night sweats due to hyper metabolism
Anorexia due to spleen compressing stomach
Hyperleukostasis
Gout as high cell turnover
Increased viscosity due to increased cells
Have granulocytes at different stages

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5
Q

What do they not have

A

Neutropenia - raised

Thrombocytopenia - can get thrombocytosis

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6
Q

What causes weight loss

A

Hypermetabolic state

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7
Q

What does hyperleukostasis cause

A

Fundal haemorrhage
Venous congestion
Altered consciousness
Resp failure

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8
Q

What is important not to do due to increased viscosity

A

DO NOT TRANSFUSE

Anaemia is the only thing that is keeping viscosity at bay

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9
Q

What are lab features of CML

A

High WCC - extremely
Variable platelet - can be high due to inflammation
Whole spectrum of myeloid cells at different stages of maturation
Urate and B12 increased
Anaemia

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10
Q

What does blood film show

A

Increased cells and different types of white cells at different stages

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11
Q

What will bone marrow and blood cells contain

A

Philadelphia chromosome

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12
Q

What is diagnostic

A

Bloods
Blood film -
Philadelphia +Ve
Bone marrow = diagnostic

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13
Q

What is 1st line Rx in CML

A

Tyrosine kinase inhibitor (direct inhibitor of BCR-ABL on Philadelphia chromosome)
Known as Imaticinib
Normal life expectancy if maintain remission
Either take tablet for years or life

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14
Q

Other Rx options

A

Interferon alpha
Allogenic stem cell transplant - do this if relapse
Chemo NOT effective as can never get rid of all cells (used to be only option so used to be incurable)

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15
Q

What is most common leukaemia in adults

A

AML

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16
Q

How does it occur

A 
Primary
- Down's
- RT
' Chemo 
- Fanconi
Secondary transformation of myeloproliferative disorder
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17
Q

What happens in AML

A

Leukaemic cells do not differnetiate
Just proliferate
Leads to bone marrow failure
Rapid aggressive and fatal

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18
Q

What are features of AML

A 
Bone marrow failure 
Infiltration - HSM 
Bone pain
Skin involvement 
CNS = rare
Usually elderly
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19
Q

What suggests poor prognosis

A

> 60
20% blasts after chemo
Do not differentiate into different cell lines
Certain cytogenetics
APML t(15,17) can present in medical emergency
- DIC
- Haemorrhage
- Continuous therapy needed in these patients

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20
Q

How do you Dx / essential investigation

A 
Blood count + film
Bone marrow aspiration = diagnostic 
Cytogenetics/ immunophenotype to guide Rx 
CSF - more in ALL as CSF spread 
Targeted genetics
Increased use of NGS myeloid gene panels
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21
Q

What will blood count and film show

A 
AUER RODS 
WCC - high or low (usually high) 
Neutropenia
Thrombocytopenia
Anaemia 
Circulating leukaemic cells
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22
Q

What confirms Dx

A

Bone marrow aspirate
Blasts >20% = Dx
If 15% = myelodysplasia

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23
Q

If infiltrate CNS what do you get

A

Headache
CN palsy
More common in ALL

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24
Q

What genes and what do they suggest about prognosis

A 
FLT3 = worse but drugs to target
NPM1 = better
IDH1 = drugs to target
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25
Q

How do you treat

A

Supportive
Chemotherapy
Allogenic stem cell to consolidate remission and cure

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26
Q

What is supportive care

A

Blood transfusion
Platelet support
Suport neutropenic sepsis risk

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27
Q

What is remission

A

Blood count returned to normal state

Blasts <5%

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28
Q

What are new treatments

A 
ATRA  - All trans retinoic acid 
- Continuous therapy against t(15,17) of RAR gene - APML type of AML
ATO
Targeted Ab against cell receptors 
New delivery systems
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29
Q

What is myelodysplastic syndromes

A

Acquired clonal disorders of bone marrow common in elderly
Bone marrow trying to produce mature cells but never quite make it to maturity
Blasts >15% but less than <20%
Pre-leukaemic
RF = smoking / previous chemo or RT

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30
Q

How does it present

A

Classically present with low blood count / cytopenia in peripheral blood but busy bone marrow full of pre-cursor

Bone marrow failure
Macrocytic anaemia 
Pancytopenia
HSM
Will progress to AML
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31
Q

How do you Rx

A

Supportive - transfusion
Few effective therapies
Chemo
Stem cell transplant in the younger

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32
Q

What are myeloproliferative disorders

A

Stem cell disorder that results in certain type of end cell / mature cell

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33
Q

What is linked to myeloproliferative disorders and what do they have potential to do

A

JAK2 mutation as means can produce cells e.g. red cells without EPO
Turns of the stop button so just over proliferative

Now used to Dx and patients no longer require bone marrow aspirate

Pre-malignant
Transform to AML

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34
Q

What are types of myeloproliferative disroder

A

Polycythermia vera - red cell
Essential thrombocythaemia - platelet
Idiopathic myelofibrosis - haemopoetic stem cell
CML - WBC

35
Q

What is polycythaemia vera

A

Clonal proliferation of marrow stem cell leading to excess red cells
Often neutrophils and platelet increased as well

36
Q

How does it present

A 
Itch and headache = very common 
Raised Hb
Hyperviscosity 
Headache
Plethroic appearance 
Itch 
Painful hands and feet 
Vascular occlusion / thrombosis 
Splenomegaly causing feeling. of abdominal fullness 
Gout 
Low ESR
Hypertension 
Haemorrhage
37
Q

What is big risk

A

TIA / stroke

38
Q

What causes haemorrhage

A

Abnormal platelets

39
Q

How do you investigate

A

FBC / film
U+E, LFT, ferritin, urate, LDH
JAK2 +ve
Cytogenetics to differentiate from CML

40
Q

What does FBC show

A

Raised Hb + haematocrit
Tend to have raised WCC / platelet
MCV may be low as iron deficiency + low ferritin

41
Q

What should you look for if raised Hb

A

Other causes
Low sats
Smoker
COPD / lung disease

42
Q

What is standard Rx

A

Venesection + aspirin

43
Q

What is aim

A

To keep haematocrit below 0.45 in M and 0.43 in F

To prevent stroke and MI

44
Q

What are other options

A

Hydroxycarbamide - suppress platelet

Ruxolitinimb - JAK2 inhibitor

45
Q

What are complications

A

Stroke
Bone marrow failure if secondary myelofibrosis occurs
Transformation to AML

46
Q

What are other causes of polycythaemia (cause same Sx)

A

COPD / lung disease / low sats - look for this
Altitiude
OSA
Excessive erythropoetin - can be caused by renal tumour
Dehydration / alcohol / diuretics causes relative

47
Q

How do you differentiate between true polycythaemia and relative

A

Red cell mass studies - will be high if true

48
Q

If JAK2 -ve and no obvious 2 cause for polycythameia what should you do

A 
ABG
ABdo USS
Serum eryhropoetin
Bone marrow aspiration
Cytogenetics
49
Q

What is essential thrombocythaemia

A

Raised platelets

50
Q

What mutation

A

JAK2

CARL

51
Q

What symptoms

A 
Arterial and venous thrombosis
Digital ischaemia
Gout
Mild splenomegaly
Normal ferritin
52
Q

How do you Rx

A

Manage vascular RF

Aspirin + hydroxycarbamide to get platelet down as high risk of thrombosis

53
Q

What can it progress too

A

Secondary myelofibrosis

AML

54
Q

What is idiopathic myelofibrosis

A

Fibrosis of bone marrow due to hyperplasia of abnormal megakaryocytic / cell lines
Cytokines cause release of platelet derived growth factor and stimulation of fibroblast
Can be primary or secondary to polycythaemia or essential thrombocythaemia

55
Q

What does this lead too

A

Haemotopoeisis developing in liver and spleen as can’t occur in marrow
Can cause HSM + portal hypertension

56
Q

How does it present

A 
Bone marrow failure
- Anaemia
- Low WCC 
Elderly + extreme fatigue
Massive splenomegaly
Hypermetabolic - weight loss / night sweats
Symptoms of cytopenia
Thrombotic events
57
Q

What are lab results

A 
Anaemia
Can get high or low WCC  depending on disease 
High or low platelet
High urate
High LDH
58
Q

What can you not too

A

Bone marrow biopsy as fibroses so just get dry tap

Trephine will be fibrotic and hyper cellular

59
Q

What is seen on film

A

Tear drop poikilocytes

60
Q

How do you Rx

A

Transfusion + supportive
Hydroxycarbamide
Ritoxicilinum - JAK2 inhibitor
Allogenic stem cell transplant = only curative

61
Q

How do you assess raised Hb / haematocrit

A 
History 
Examination
Bloods 
JAK2
USS to look for splenomegaly 
EPO
Red cell mass studies
Bone marrow = rarely done
62
Q

What is important in the Hx

A

Any reasons for polycythaemia e.g. smoking
Any symptoms suggestive of polycythamia vera
Assess thrombotic risk

63
Q

What do you look for in examination

A

Splenomegaly
Chest signs
O2 sats

64
Q

What bloods

A

Repeat FBC, U+E, LFT, urate, LDH, ferritin

65
Q

What confirms myelproliferative disorder

A

+ve JAK2 mutations

66
Q

What does EPO tell you

A

If low = primary polycythaemia
Normal = unhelpful
If high = secondary

67
Q

What are red cell mass studies useful for

A

Work out if true or apparent polycythaemia

68
Q

What causes primary thrombocytosis

A 
Overproduction in bone marrow usually due to myeloproliferative disorder
Essential thrombocytosis 
Myelofibrosis
Ppolycythaemia 
CML
69
Q

What causes secondary

A 
Systemic response to infection
Inflammation - RA
Tissue damage - post surgery 
Malignancy
Iron  or B12 deficiency
70
Q

What could you ask in history

A 
Infection
Surgery
Bleeding 
Weight loss
Joint pain
Pruritus
71
Q

What do you look for in examination

A

Splenomegaly

Signs of malignancy / inflammation / infection

72
Q

What investigations

A 
FBC, film, U+E, LFT, urate, LDH
CRP/. ESR
Ferritin
JAK2
USS/. CT
73
Q

What can help differentiate

A

Primary patient usually well
- Itch / thrombosis / splenomegaly often associated

Secondary patient usually unwell

74
Q

Background

A

OK

75
Q

Where are myeloid precursor cells supposed to liver

A

In BM = only place

76
Q

What happens if begins to grow out of control e.g AML / myelodysplasia

A

Very busy bone marrow
Increasing cells in blood count as leak out
Abnormal cells in BM expand in number and crowd out normal precursor
BM starts to fail in ability to produce normal cells = cytopenia
Abnormal cells leak out into blood and can see leukaemia cells

77
Q

What can AML purely present with

A

Cytopenia

May just be neutropenic but will eventually get all

78
Q

Overproliferation of immature cells

A

AML

79
Q

Overproliferation of mature cells

A

ET

80
Q

Similarity between myeloproliferative and myelodysplasia

A

Both myeloid
Both slow moving
Both oveproliferation of myeloid precursor

81
Q

Difference

A

Myeloproliferative

  • Cells still normal enough to make it to maturity of whatever lineage
  • Leads to too many blood cells
  • Aim to get cell count down

Myelodysplasitc

  • Cells proliferate but do not survive
  • BM can look similar as full of precursor but blood count low / cytopenia
82
Q

How does CML overlap with both

A

Proliferation of WCC - neutrophilic / monocytosis
Get loss of mature RBC and platelet formation
Often a leucocytosis with anaemia / thrombocytopenia or both

83
Q

What can result from myeloproliferative / dysplasia

A

Secondary AML
Cells already have a genetic abnormality so more likely to transform
More difficult to Rx if secondary as more mutations

Haematology (13 decks)

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