Acute Leukaemias

Question 1

What is acute leukaemia?

Answer 1

A very aggressive disease

Question 2

What is the pathophysiology of acute leukaemia?

Answer 2

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

Question 3

How does acute leukaemia develop?

Answer 3

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

Question 4

How do blood results present with acute leukaemia?

Answer 4

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)

Question 5

What is the clinical presentation of bone marrow failure in acute leukaemia patients?

Answer 5

Anaemia - fatigue/pallor
thrombocytoponeia - bruising, bleeding
neutropenia - infection
bone pain
weight loss

Question 6

What is the clinical presentation of organ infiltration in acute leukaemia?

Answer 6

lymphadenopathy, sphlenomegaly, CNS involvement (seizures), gum hypertrophy

Question 7

How is acute leukaemia diagnoses?

Answer 7

FBC, u+e, urate, coagulation, imaging, bone marrow aspiration, biopsy

Question 8

What is the initial management of acute leukaemia?

Answer 8

• 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

Question 9

What is the induction phase of acute leukaemia treatment?

Answer 9

• Lasts 4-6 weeks

- intensive chemotherapy in order to eradicate leukaemia and induce remission

Question 10

What is the consolidation/intensification phase of acute leukaemia treatment?

Answer 10

Lasts 4-12 weeks

further high dose chemo to eradicate any residues of leukaemia

Question 11

What is the prolonged maintenance phase of acute leukaemia treatment?

Answer 11

• lasts 2-3 years
• lower dose outpatient treatment
• prevent relapse

Question 12

What are the stages of acute leukaemia treatment?

Answer 12

Induction phase, intensification/consolidation, prolonged maintenance

Question 13

What is CNS directed therapy and when is it given?

Answer 13

Preventative intrathecal chemotherapy, given throughout all phases of treatment in order to prevent relapse

Question 14

What supportive care is given to acute leukaemia patients?

Answer 14

• 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

Question 15

What is tumour lysis syndrome and how is it prevented?

Answer 15

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.

Question 16

How does allopurinol prevent tumour lysis syndrome?

Answer 16

It breaks down uric acid and prevents the formation of it. Can interact with azathioprine

Question 17

How is febrile neutropenia prevented in acute leukaemia?

Answer 17

IV antibiotics, antifungal, antivirals, granulocytes

Question 18

What is acute myeloid leukaemia?

Answer 18

An over production of immature monocytes and granulocytes. The most common leukaemia in adults

Question 19

What are the prognostic factors for AML?

Answer 19

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

Question 20

Who is ALL common in?

Answer 20

Children

Question 21

Which factors give poor prognosis for ALL?

Answer 21

• 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

Question 22

Which factors can lead to ALL?

Answer 22

Can be inherited diseases/enivronmental exposure

some infections

Question 23

What is risk based treatment assignment in ALL?

Answer 23

• clinical trials encouraged
• specific protocols according to risk of treatment failure
• minimal residual disease at day 28 is important

Question 24

Which drugs are used in the induction period for ALL?

Answer 24

gluccocorticoid, vincristine, l-aspariginase, anthracycline, intrathecal chemo

Question 25

Which drugs are used during the consolidation phase for ALL?

Answer 25

Gluccocorticoid, high dose methotrexate, low dose cytrabine, l-asaprigiinase, intrathecal chemo

Question 26

Which drugs are used during the intensification phase of ALL?

Answer 26

Gluccocorticoid, vincristine, l-aspariginase, anthracycline, intrathecal chemo

Question 27

Which drugs are used during the maintenance phase for ALL?

Answer 27

Gluccocorticoid, methotrexate, mercatopurine, vincristine, intrathecal chemo

Question 28

What is asparaginase and why is it important for leukaemia cells?

Answer 28

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.

Question 29

What is relapse associated with in ALL and how is treatment approached following this?

Answer 29

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

Question 30

What is CAR-T?

Answer 30

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