Theme 7 Haematology: Acute Leukaemia and MDS Flashcards
Why does acute leukaemia occur?
- a result of accumulation of early myeloid (AML) or lymphoid (ALL) precursors in the bone marrow, blood and other tissues
- occurs by somatic mutation in a single cell within a population of early progenitor cells (this cell then increases in number)
What is the median age at presentation for AML?
69
What are the clinical features of AML?
Presents with features of bone marrow failure:
- anaemia, fatigue, pale
- infections as white cells aren’t working
- easy bruising and haemorrhage as platelet count is low
What are the haematological features of AML?
- anaemia –> Hb is low
- low or high WCC with circulating primitive leukaemia cells
- low platelets
How can we diagnose AML?
- morphology of cells on blood film
- immunological markers
- cytogenetics (chromosomes)
- certain abnormalities correlate with prognosis e.g t(8;21) inv (16) and t (15:17)
Which factors are important in determining prognosis from AML?
- age
- chromosomes (good risk, intermediate risk or poor risk chromosomes)
- molecular features - NPM1 (good risk marker) and FLT3-ITD (bad risk marker)
- extramedullary disease
- disease that doesn’t respond to treatment
What does ‘intensive chemotherapy’ entail?
- 3-4 cycles of intravenous cytotoxic drugs given centrally
- life on hold for 6 months
What are the risks of intensive chemotherapy?
death sepsis alopecia infertility tumour lysis
How do we determine who should have intensive chemotherapy and who should have non-intensive chemotherapy?
- age
- co morbidity
- body habitus (what they look like)
- lifestyle decisions (smoker, alcoholsm)
- cytogenetics
- molecular information
You should start immediate intensive chemotherapy in which patients?
- critically ill patients with rapidly progressive disease with respiratory/neurological compromise
- there is no proven benefit of early treatment in any other patients
What are the side effects of intensive therapy?
alopecia nausea and vomiting potential loss of fertility bruising/bleeding fatigue weight loss altered taste sensation infection mortality
Why is survival of AML so poor?
- age
- high proportion of unfavourable cytogenetics
- frequent involvement of more immature leukaemic precursor clone
- multi drug resistance
- higher levels of co morbidity
- haem disorders
When does typical relapse in AML occur?
18 months after intensive chemotherapy
Give 4 non-intensive treatment options for AML
- Low dose chemotherapy (cytarabine)
- Hypomethylating agents
- azacytidine
- not cytotoxic but alter proliferation of leukaemia cells - Venetoclax
- BCL2 inhibitor
- allows cancer cells to apoptose
What does the FLT3 receptor tyrosine kinase mutation mean?
- this marker is a poor risk marker on the surface of the leukaemia cells
- impacts on disease free survival
Who has FLT3 mutations?
- approx 30% of AML patients
- FLT3 ITD mutation
- common
Which FLT3 inhibitors are in development?
midostaurin
quizartinib
What are the common complications of AML?
neutropenic sepsis
bleeding
What is the clinical presentation of acute lymphoblastic leukaemia (ALL)?
- fatigue
- bruising/bleeding
- weight loss
- night sweats
- hepatosplenomegaly
- lymphadenopathy
- mediastinal mass
What are the 4 components of treatment of ALL?
- Induction (8 weeks)
- Intensification/ CNS prophylaxis (4 weeks)
- Consolidation (20 weeks)
- Maintenance (2 years)
What are the current options for relapsed disease?
- further intensive chemotherapy
- blinatumomab
- inotuzumab
What is blinatumomab?
- 2 antibodies stuck together
- brings T cell in direct contact with tumour cell so it can be killed
- less toxic than chemotherapy
What is inotuzumab?
-antibody with chemotherapy drug attached that sticks to CD22
What is neutropenic sepsis?
main/life-threatening complication of chemotherapy
What are the symptoms and treatment of neutropenic sepsis?
symptoms: fever, hypotension, organ impairment
treatment: broad spectrum IV antibiotics
What is MDS?
- myelodysplasia
- “pre-leukaemia”
- blood cell isn’t formed properly
- a heterogenous group of clonal bone marrow stem cell disorders that result in ineffective haematopoiesis with reduced production of one or more of the peripheral blood cell lineages
What are the features of MDS?
- dysplasia
- inefficient haematopoiesis
- cytopenias
- increased risk of transformation to AML
How do you treat low risk MDS?
- may only need to monitor patient
- only treat if symptomatic
- erythropoietin for anaemia once a week
How do you treat high risk MDS?
if fit enough treat as per AML with intensive chemotherapy and bone marrow transplant
if not, consider azacytidine
