Acute Leukaemias Flashcards
What is acute leukaemia?
A very aggressive disease
What is the pathophysiology of acute leukaemia?
Failure for cells to differentiate and mature into functional cells. Uncontrolled proliferation of immature leukocytes, which leads to an accumulation of immature cells. Has a 2 week doubling time
How does acute leukaemia develop?
Increased blast cells causes symptoms. Production of normal blood cells is depleted which leads to fewer functional cells and bone marrow function decreases, leading to infection and anaemia due to reduce platelets
How do blood results present with acute leukaemia?
Accumulation of immature and ineffective white blood cells leads to high white blood cells but the number of functioning cells is low (neutrophils, platelets, anaemic)
What is the clinical presentation of bone marrow failure in acute leukaemia patients?
Anaemia - fatigue/pallor thrombocytoponeia - bruising, bleeding neutropenia - infection bone pain weight loss
What is the clinical presentation of organ infiltration in acute leukaemia?
lymphadenopathy, sphlenomegaly, CNS involvement (seizures), gum hypertrophy
How is acute leukaemia diagnoses?
FBC, u+e, urate, coagulation, imaging, bone marrow aspiration, biopsy
What is the initial management of acute leukaemia?
- rapid diagnosis and early access to treatment (treatment is largely clinical trial based)
- emergency treatment of complications: hydration and correction of electrolyte imbalances, treatment of any infection
- HLA typing for blood transfusions
- sperm/egg banking
- mental health/wellbeing
- suppress menses
What is the induction phase of acute leukaemia treatment?
- Lasts 4-6 weeks
- intensive chemotherapy in order to eradicate leukaemia and induce remission
What is the consolidation/intensification phase of acute leukaemia treatment?
Lasts 4-12 weeks
further high dose chemo to eradicate any residues of leukaemia
What is the prolonged maintenance phase of acute leukaemia treatment?
- lasts 2-3 years
- lower dose outpatient treatment
- prevent relapse
What are the stages of acute leukaemia treatment?
Induction phase, intensification/consolidation, prolonged maintenance
What is CNS directed therapy and when is it given?
Preventative intrathecal chemotherapy, given throughout all phases of treatment in order to prevent relapse
What supportive care is given to acute leukaemia patients?
- supportive treatments to treat the symptoms and minimise any complications that may be associated with chemotherapy
- prevention of tumour lysis syndrome
- prevention of febrile neutropenia
- prevention of emesis
- pcp prophylaxis
What is tumour lysis syndrome and how is it prevented?
A complication of treating high cell count disease. Cell contents leak into the plasma, causing hypokalaemia, hypercalcaeima, urate precipitation in the urinary tract and renal dysfunction. It is pre treated with aggressive hydration and allopurinol/asburicase.
How does allopurinol prevent tumour lysis syndrome?
It breaks down uric acid and prevents the formation of it. Can interact with azathioprine
How is febrile neutropenia prevented in acute leukaemia?
IV antibiotics, antifungal, antivirals, granulocytes
What is acute myeloid leukaemia?
An over production of immature monocytes and granulocytes. The most common leukaemia in adults
What are the prognostic factors for AML?
Good/intermediate/poor risk
Adults with multiple morbidities and frail, no aggressive treatments
over 50 y/o, remission rate is higher
If the patient has a higher percentage of blasts after the first course of treatment, this leads to short remissions and poor survival
If the patient has a secondary acute myeloid leukaemia after chemo
Who is ALL common in?
Children
Which factors give poor prognosis for ALL?
- unfavourable cytogenetics
- age
- male sex
- high WBC count
- presence of CNS disease
- poor response to initial treatment - if full response is not achieved at day 28
Which factors can lead to ALL?
Can be inherited diseases/enivronmental exposure
some infections
What is risk based treatment assignment in ALL?
- clinical trials encouraged
- specific protocols according to risk of treatment failure
- minimal residual disease at day 28 is important
Which drugs are used in the induction period for ALL?
gluccocorticoid, vincristine, l-aspariginase, anthracycline, intrathecal chemo
Which drugs are used during the consolidation phase for ALL?
Gluccocorticoid, high dose methotrexate, low dose cytrabine, l-asaprigiinase, intrathecal chemo
Which drugs are used during the intensification phase of ALL?
Gluccocorticoid, vincristine, l-aspariginase, anthracycline, intrathecal chemo
Which drugs are used during the maintenance phase for ALL?
Gluccocorticoid, methotrexate, mercatopurine, vincristine, intrathecal chemo
What is asparaginase and why is it important for leukaemia cells?
Asparaginase is an enzyme which converts asparagine to aspartic acid and ammonia. Asparagine is an amino acid which is essential for protein synthesis. Leukaemia cells are unable to make asaparagine, therefore treating with l-asapariginase depletes asparagine and inhibits protein synthesis.
What is relapse associated with in ALL and how is treatment approached following this?
Associated with poorer outcomes.
If it occurs extramedullary, it is associated with better outcomes. Use localised therapy and a second full course of systemic chemo.
Allogenic transplants or cart can be used
What is CAR-T?
Taking blood with t cells from a patient, creating car t cells that react to cancer, grow, inject back into the patient and they kill the cancer via t cell mechanisms
