Theme 7 Haematology: Acute Leukaemia and MDS

Question 1

Why does acute leukaemia occur?

Answer 1

• 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)

Question 2

What is the median age at presentation for AML?

Answer 2

69

Question 3

What are the clinical features of AML?

Answer 3

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

Question 4

What are the haematological features of AML?

Answer 4

• anaemia –> Hb is low
• low or high WCC with circulating primitive leukaemia cells
• low platelets

Question 5

How can we diagnose AML?

Answer 5

• 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)

Question 6

Which factors are important in determining prognosis from AML?

Answer 6

• 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

Question 7

What does ‘intensive chemotherapy’ entail?

Answer 7

• 3-4 cycles of intravenous cytotoxic drugs given centrally

- life on hold for 6 months

Question 8

What are the risks of intensive chemotherapy?

Answer 8

death
sepsis
alopecia
infertility
tumour lysis

Question 9

How do we determine who should have intensive chemotherapy and who should have non-intensive chemotherapy?

Answer 9

• age
• co morbidity
• body habitus (what they look like)
• lifestyle decisions (smoker, alcoholsm)
• cytogenetics
• molecular information

Question 10

You should start immediate intensive chemotherapy in which patients?

Answer 10

• critically ill patients with rapidly progressive disease with respiratory/neurological compromise
• there is no proven benefit of early treatment in any other patients

Question 11

What are the side effects of intensive therapy?

Answer 11

alopecia
nausea and vomiting
potential loss of fertility
bruising/bleeding
fatigue
weight loss
altered taste sensation
infection
mortality

Question 12

Why is survival of AML so poor?

Answer 12

• age
• high proportion of unfavourable cytogenetics
• frequent involvement of more immature leukaemic precursor clone
• multi drug resistance
• higher levels of co morbidity
• haem disorders

Question 13

When does typical relapse in AML occur?

Answer 13

18 months after intensive chemotherapy

Question 14

Give 4 non-intensive treatment options for AML

Answer 14

1. Low dose chemotherapy (cytarabine)
2. Hypomethylating agents
   - azacytidine
   - not cytotoxic but alter proliferation of leukaemia cells
3. Venetoclax
   - BCL2 inhibitor
   - allows cancer cells to apoptose

Question 15

What does the FLT3 receptor tyrosine kinase mutation mean?

Answer 15

• this marker is a poor risk marker on the surface of the leukaemia cells
• impacts on disease free survival

Question 16

Who has FLT3 mutations?

Answer 16

• approx 30% of AML patients
• FLT3 ITD mutation
• common

Question 17

Which FLT3 inhibitors are in development?

Answer 17

midostaurin

quizartinib

Question 18

What are the common complications of AML?

Answer 18

neutropenic sepsis

bleeding

Question 19

What is the clinical presentation of acute lymphoblastic leukaemia (ALL)?

Answer 19

• fatigue
• bruising/bleeding
• weight loss
• night sweats
• hepatosplenomegaly
• lymphadenopathy
• mediastinal mass

Question 20

What are the 4 components of treatment of ALL?

Answer 20

1. Induction (8 weeks)
2. Intensification/ CNS prophylaxis (4 weeks)
3. Consolidation (20 weeks)
4. Maintenance (2 years)

Question 21

What are the current options for relapsed disease?

Answer 21

• further intensive chemotherapy
• blinatumomab
• inotuzumab

Question 22

What is blinatumomab?

Answer 22

• 2 antibodies stuck together
• brings T cell in direct contact with tumour cell so it can be killed
• less toxic than chemotherapy

Question 23

What is inotuzumab?

Answer 23

-antibody with chemotherapy drug attached that sticks to CD22

Question 24

What is neutropenic sepsis?

Answer 24

main/life-threatening complication of chemotherapy

Question 25

What are the symptoms and treatment of neutropenic sepsis?

Answer 25

symptoms: fever, hypotension, organ impairment
treatment: broad spectrum IV antibiotics

Question 26

What is MDS?

Answer 26

• 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

Question 27

What are the features of MDS?

Answer 27

• dysplasia
• inefficient haematopoiesis
• cytopenias
• increased risk of transformation to AML

Question 28

How do you treat low risk MDS?

Answer 28

• may only need to monitor patient
• only treat if symptomatic
• erythropoietin for anaemia once a week

Question 29

How do you treat high risk MDS?

Answer 29

if fit enough treat as per AML with intensive chemotherapy and bone marrow transplant

if not, consider azacytidine