Introduction to Leukaemia Flashcards
Define leukaemia
Malignancy characterised by unregulated clonal proliferation of one haematological cell type.
Clinical features of acute leukaemia
- > 20% immature blasts
- Prominent anaemia and thrombocytopenia
- WCC variable
- Mild lymphadenopathy and splenomegaly
Clinical features of chronic leukaemia
- Mild anaemia and thrombocytopenia
- Raised WCC
- Prominent lymphadenopathy and splenomegaly§
What factors influence prognosis?
- Age
- WCC at presentation
- Cytogenetics and karyotype
- Response to initial treatment
- MRD after tx
Why do we get BM failure in acute leukaemia?
Crowding out of normal cells by the leukaemic cells
What happens in leukostasis, and how does it present?
- Accumulation of blasts in the microcirculation and impaired perfusion
- Release cytokines and blast death products, which burden the kidneys
- Lungs: infiltrates and hypoxaemia
- CNS: fluctuating LOC, stroke
- Retinal haemorrhage: increased risk of ICH
- Priapism
What mutation is associated with AML in Trisomy 21?
GATA-1 mutations
Morphological features in APML?
- Biobed nuclei
- Faggott cell
- Hypergranularity
Blast morphology in ALL
- Large cells
- High nucleocytoplasmic ratio
- Thin rim of cytoplasm
- No granules
How do you differentiate between leukaemic infiltration of skin and petechiae caused by thrombocytopenia?
Leukaemic infiltration - raised papules on skin
Petechiae - not raised
What do you see in tumour lysis syndrome?
- Increased LDH and uric acid
- increased phosphate
- Hyperkalaemia
- Hypocalaemia
What are the principles of diagnosis?
- Morphology (light microscopy)
- Immunohistochemistry -although no longer done much
- Immunophenotyping
- Cytogenetics
- Molecular genetics
What are some established aetiological triggers in ALL?
- Ionising radiation
- Viruses e.g. EBV, HTLV-1
- Dyes - long exposure
- Cytotoxic drugs (Can cause a secondary leukaemia)
Cytochemistry in blasts
MPO and SBB indicate myeloblasts and we need >3% blasts to stain positive for these, to qualify as myeloblasts.
NSE - monocytic differentiation
Chloroactetate esterase: Bright red granular staining in promyelocytes onwards.
PAS: Positive in L1, L2; negative in l3
FITC in immunophentoyping
Fluoroscein Isothiocyanate
PE in immunophenotyping
Phycoerythrin
Why is it difficult to differentiate lymphocytes from M0 myeloblasts?
M0 myeloblasts don’t have granules, so they don’t stain for MPO, and they don’t have auer rods.
Usefulness of different techniques in detecting MRD
Morphology and cytogenetics: can’t detect
FISH (cytogenetics) is a bit better
But the best technique is MOLECULAR GENETICS:
- PCR
- Multiparameter flow cytometry
