Haematological Cancer: Leukaemia Flashcards
(48 cards)
1
Q
Leukaemia vs Lymphoma
A
- liquid tumour vs solid
- arises in bone marrow vs arises in
lymph nodes - lymphoid/myeloid vs lymphoid
2
Q
Leukaemia Aetiology:
A
- oncogene is a mutated gene that
contributes to the development of
cancer - tumour suppressor gene is a bit
like an anti-oncogene - oncogene triggered by exposure to
genetic/environmental modifiers - leukaemia occurrs
3
Q
Aetiology of Leukaemia
A
4
Q
How can we classify leukaemia?
A
- acute vs chronic
- myeloid vs lymphoid
5
Q
Acute Leukaemia features:
A
- proliferation (division) of immature
cells - rapid onset
- can have a devastating course if
untreated - younger patients
- immature cells (blasts) in the
blood/marrow
6
Q
Chronic Leukaemia features:
A
- proliferation (division) of mature
cells - gradual onset
- indolent course
- older patients
- mature cells in the blood/marrow
7
Q
Lymphoid classification of leukaemia:
A
- cells from lymphocyte line
8
Q
Myeloid classification of leukaemia:
A
- granulocytes
- monocytes
- RBCs
- megakaryocytes
9
Q
4 main categories of leukaemia and key points summary at end
A
10
Q
Leukeamia presents with:
A
- signs of bone marrow failure:
anaemia, thrombocytopenia,
conjunctivital pallor,
bruising/bleeding, petechial rash - infections: patients may become
neutropenic produce too few
neutrophils hence get frequent
infections: tonilitis, cellulitis, ulcer,
sores, candida fungal (especially
fungal if immunocomprimised) see
spores in lungs - tissue infiltration
- other: breathless, fatigue, headache, retinal haemarrhoges, cytokine release trigger clots and bleeds
11
Q
Signs of bone marrow failure:
A
insert conjunctvital pallow
12
Q
Signs of bone marrow failure:
A
bruising/bleeding because low platelts
insert bruised legs
13
Q
Signs of bone marrow failure:
A
brusing/bleeding signs
low platelts
insert nose bleeds
14
Q
Signs of bone marrow failure:
A
petechial rash
insert bottom left
15
Q
Tissue infiltration:
A
mediastinal widening chest x ray
insert
specific in subtype of lymphoblastic leukaemia TLL; thoracic lymphadenopathy
16
Q
Tissue Infiltration
A
enlarged spleen and liver down toward illiac fossa
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17
Q
Tissue infiltration
A
Gum thickening
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18
Q
Tissue Infiltration:
A
neurologic involvement, involvement of cranial nerve: occular motor nerve pull
19
Q
Tissue Infiltration
A
skin involvement
20
Q
testicular tissue infiltration in which type of leukeamia
A
acute lymphoblastic leukeamia ALL
21
Q
Diagnosis of leukaemia:
A
- history
- examination
- blood count:
- morphology (blood film)
- blood biochemistry
- virology
- bone marrow biopsy = definitive
diagnosis - genetic testing = chromosomal
microarray, single gene sequencing - immunophenotyping
- flow cytometry
22
Q
Bone marrow biopsy
A
- needle inserted into the back of the
iliac crest - patient lying flat
- take a sample of spongy bone
- deep to cortical bone
- stain and look through microscope
- other types of genetic testing
23
Q
other types of genetic testing:
A
- chromsomal microarray is much
quicker than karyotype - unravel dna and look for single
gene disorders - genetic
- acquired mutations
- look at whole karyotype
24
Q
Immunophenotyping/Flow cytometry:
A
- immunophenotyping looks for the presence or absence of cell antigens that can give us clues at to blood abnormalities
- flow cytometry uses monoclonal antibodies to see scattered light from laser
25
ALL:
- stands for
- when common
- presents with (2)
- cell types
- risks and treatments
- acute lymphoblaastic leukaemia
- presents with:
- bone marrow involvement
- bulky disease (mediastinal
nodes)
- B cell or T cell
- risk of cerebro-spinal fluid CSF
involvement
- treatment directed at CSF/ analysis
regularly of CSF
26
B cell ALL:
- stands for
- features (3)
- B cell acute lymphoblastic
leukaemia
- Bone marrow failure
- Big spleen (splenomegaly)
- CD10 and CD19 higher number on
genetic phenotyping
27
T cell ALL:
- stands for
- features (3)
- T cell acute lymphoblastic
leukaemia
- Teenage boys
- thoracic lymphadenopathy:
mediastinal widening on CXR
- Low CD numbers CD5,7 on genetic
phenotyping
28
19 year old boy who has a chest x ray that showed mediastinal widening and he had lots of blasts on his blood film, what to consider?
T cell leukaemia
29
AML:
- stands for
- features (5)
- acute myeloid leukaemia
- >20% blasts in marrow/film,
spectrum disorder with bone
marrow failure (myelodysplasia)
have to have more than 20% blasts
- myelodysplasia will only lead to
AML but not always! not other
leukaemias
- tend to see in older patients:
median age 65
- auer rods are diagnostic ***
30
Auer rods
precipitation of granules and proteins
insert diagram
31
Acute Promyelocytic Leukaemia:
- variant of
- features (microscopically)
- associated with
- Rx
- variant of AML
- lots of auer rods
- lots of granules
- can be associated with severe
coagulopathy: (bleeding tendancy)
- activates the clotting pathway
- causes depletion og clotting
factors
- haematological emergency**
Specific treatment:
- all trans retinoic acid ATRA
- causes promyelocytes to
differentiate/mature
blast to promyelocyte to neutrophil
32
Treatment of Acute Leukaemia:
- consider patient factors and
disease factors
- curative vs palliative
- supportive care: symptomatic:
- prevent beeding
- correct coag abnormalities
- prevent menstruation
- prevent infections
- preserve fertility
- trial vs standard of care
- systemic anti-cancer therapy:
- chemo (months/years, intense)
- radiotherapy
- bone marrow transplantation
(allogenic)
- experimental
33
CLL:
- stands for
- types of cell
- blood test results
- blood film observations (2)
- chronic lymphocytic leukaemia
- good prognosis (median survival 10
years)
- B lymphocytes
- Lymphocyte count >5x109/L but
can be very high
- small/medium sized
lymphocytes+++: film and marrow
- smear cells on blood film
34
Allogenic Transplantation
- give chemo to remove all stem cells
- collect stem cells from donor
- treat stem cells
- insert, stem cells take root in bone
marrow, hopefully produce normal
blood cells without leukaemia
35
Allogenic Transplantation Risks:
- graft failure
- graft vs host disease GvHD: graft
attacks
- infection
- fertility
- psychosocial, burden of follow up,
burden of morbidity
- relapse of leukaemia
36
venous access for chemotherapy or stem cells:
- pick line
- long term cannulas into anterior cubital fossa and into right atrium
- port through subclavian vein
(better for younger patients as
covered)
- hickman line exposed port
- risk of infection
37
Prognosis in acute leukaemia:
- fatal in weeks/months if untreated
- varies by type, age and response to
treatment
- childhood ALL can be cured in most
patients (>80%)
- AML and ALL in the elderly is poor
prognosis
- adverse risk factors:
- age >60
- male
- high WBC at presentation
- CSF involvement
- residual disease after induction
chemo
- recurrent disease
38
CLL presents:
- most commonly found
- symptoms and signs (4)
- chronic lymphoid leukaemia
- most commonly and incidental
finding: high WBC count,
asymptomatic
- generalised lymphadenopathy
- splenomegaly
- symptoms of anaemia:
autoimmune haemolytic anaemia,
bone marrow failure
- infections: reduced
immunogobulin, reduced WBC
diversity
39
An 80 year old man presents with a high lymphocyte count and is noted to have smear cells on his blood. whats the diagnosis?
chronic lymphocytic leukaemia
40
CLL special considerations:
- haemolysis screen results
- may be coombs test 9DAT) positive
- CD19+ B cell surface antigens
- genetic analysis can affect Rx
- cross-over with lymphoma:
transform to a high grade
lymphoma
- may hear small lymphocytic
lymphoma can transform
- usually no treatment required -
watch and wait = active surveillance
41
CML:
- stands for
- age incidence
- aetiology
- time
- chronic myeloid leukaemia
- older age, peak in 50 years
- mutation of stem cell for whole
myeloid line: raised levels:
- granulocytes
- monocytes
- megakaryocytes
- high platelet count
- slow course with 3 phases:
- chronic (<10% blasts0
- accelerated (10-20% blasts)
- blast crisis (>20% blasts) =
worst prognosis of three
42
CML presentation:
- very high WBC
- all granulocyte lines+immature
- often asymptomatic
- rare in young people <19
Symptoms: due to high WBC:
- due to bone marrow failure:
anaemia symptoms
- splenomegaly (massive)
- fever/sweats/weight loss
- due to leucocytosis:
- headache
- retinal bleeding
- priapism
43
CML diagnosis:
- high basophils on peripheral film is
highly specific
- high platelet counts
- very high WBC
- different phases of illness defined
by blast count
- transform to AML or ALL
44
CML aetiology:
- formation of philidelphia chromosome
- reciprocal translocation between
ABL gene on chromosome 9 and
BCR gene chromosome 22 ***
- CML
45
CML treatment:
- philadelphia chromsome results in the overproduction of a tyrosine kinase signalling protein
- increases tyrosine kinase
activity
- overproduction of myeloid cells
- specific Rx:
- tyrosine kinase inhibitor =
IMATINIB
- induces complete remission in
70% cases
- blast crisis and accelerate phase would also need chemo and surgery
46
Which of the following conditions is most likely to be associated with DAT + haemolytic anaemia?
1 = Acute lymphoblastic leukaemia
2 = Acute myeloid leukaemia
3 = Chronic lymphocytic leukaemia
4 = Chronic myeloid leukaemia
5 = Hairy Cell Leukaemia
3 = CLL
47
Which of the following is the Philadelphia Chromosome?
1 = t(15;19)
2 = t(14;18)
3 = t(9;22)
4 = t(1;7)
5 = t(9,21)
3
9&22
48
Summary slide
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