Acute Leukaemia and MDS Flashcards
What is acute leukaemia?
Result of accumulation of early myeloid (AML) or lymphoid (ALL) precursors in the bone marrow and other tissues
What are the 2 route of pathogenesis of acute leukaemia?
- Probably occurs by somatic mutation in a single cell within a population of early progenitor cells
- May arise de novo or secondary to prior chemotherapy/radiotherapy (prognosis worse) or another haematological condition
What is the median age of presentation of AML?
- Median age: 69 years
* Incidence is increasing (ageing population)
What is the survival rate of AML?
Poor survival rate compared to those <60 years old (likely due to comorbidities)
What is the clinical presentation of AML?
o Features of bone marrow failure: anaemia (pale, tired), prone to infections (temperature, chest infection), easy bruising (low platelet count) and haemorrhage
o Organ infiltration by leukaemia cells may occur e.g. spleen, liver, meninges, testes and skin
o Gum hypertrophy
o Bleeding
o Anaemia
o Neutropenic sepsis
Describe the;
a) RBC level
b) WBC level
c) platelet level
in AML?
a) Anaemia
b) Low or high WBC with circulating leukaemia cells
c) Low platelets
What is cytogenetics?
Cytogenetics is the branch of genetics that studies the structure of DNA within the cell nucleus (number and morphology of chromosomes)
How can AML be diagnosed?
o Morphology
o Immunological markers
o Cytogenetics (chromosomes): certain abnormalities correlate with prognosis e.g. t(8;21) inv(16) and t(15:17)
What are important prognostic factors in AML?
o Age (co-morbidities, more mutations driving leukaemia, poorer immune system)
o Chromosome abnormalities (good risk ones vs bad risk ones)
o Molecular features – NPM1 (good prognosis with chemotherapy) and FLT3-ITD (tend to have bad prognosis), present on cell surface
o Extramedullary disease (worse prognosis e.g. cutaneous leukaemia, CNS disease)
o Disease that doesn’t respond to treatment (refractory disease, worse prognosis)
Treatment for AML?
Intensive chemotherapy - all AML patients up to 80 years old should be considered for intensive treatment.
Describe the intensive chemotherapy given in AML
3-4 cycles of IV cytotoxic drugs given centrally (for each treatment, patient in hospital for around 4-6 weeks)
What are the risks associated with intensive chemotherapy?
o Death o Sepsis o Alopecia o Infertility o Tumour lysis Can also cause gout. o Taste is metallic
What is tumour lysis?
A group of metabolic abnormalities that can occur during the treatment of cancer, where large amounts of tumour cells are killed off (lysed) at the same time by the treatment, releasing their contents into the bloodstream.
Waste products such as uric acid from tumour cells can plug up kidneys and cause problems. Can also cause gout.
IV treatment can relieve these symptoms.
What % of AML patients can be in complete remission after one cycle of intensive chemotherapy?
80-85%
What is the treatment for high risk AML patients (e.g. not responding to chemo, have the FLT3-ITD markers)?
Chemo + bone marrow transplant
Which patients require immediate intensive therapy for AML?
Critically ill patients with rapidly progressive disease (such as WCC >100 x 109/L) with respiratory / neurological / other organ compromise
For patients with AML but a lower white count, therapy can be put on hold for a couple of days.
What needs to be done in these couple of days?
No proven benefit to early initiation of treatment, wait for cytogenetics and mutational status prior to deciding on definitive therapy.
What are the complications of intensive therapy for AML?
o Alopecia o Nausea and vomiting o Potential loss of fertility o Bruising/bleeding o Fatigue o Weight loss o Altered taste sensation o Infection o Mortality
Why is the survival rate of AML so poor?
- Age: hard to survive chemotherapy, especially with co-morbidities
- High proportion of unfavourable cytogenetics
- Frequent involvement of more immature leukaemia precursor clone
- Multi-drug resistance (MDR1/P-glycoprotein)
- Antecedent haem disorders
- Higher levels of co-morbidity
AML is an aggressive disease. How soon after finishing intensive chemo does it tend to relapse? When is it likely cured?
o Typically relapses within 18 months of intensive chemotherapy
o At 4 years post chemo, likely cured
What is Cytarabine? Used to treat?
A chemotherapy medication used to treat acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and non-Hodgkin’s lymphoma.
Who would Cytarabine be useful for? Who is it not useful for?
o Widely used
o Useful in those not suitable for intensive chemotherapy
o Not good for patients with adverse cytogenetics
o Can cause side effects which may decrease quality of life without prolonging survival for that long
Why are hypomethylating agents?
Drugs that inhibits DNA methylation –> can alter proliferation of leukaemia cells. Used in AML.
Benefits of hypomethylating agents?
Well tolerated by ‘unfit’ elderly patients
2 examples of hypomethlyating agents?
Decitibine (dec) and azacytidine (aza)
What are 2 examples of chemo drugs used in low intensive therapy in AML?
- low dose Cytarabine
2. hypomethylating agents
What is Venetoclax? Mechanism?
A form of targeted therapy instead of chemotherapy (used in AML).
Restores apoptosis of cancer cells through BCL-2 inhibition (cancer cells die).
What would Venetoclax be used in combination with?
Azacytidine or low dose Cytarabine (increases survival)
What 2 proteins present on cell surfaces can be molecular markers of AML?
- FLT3-ITD (tend to have bad prognosis)
2. NPM1 (tend to have good prognosis with chemo)
