Acute Leukaemia's

Question 1

What is the most common age of onset of AML?

Answer 1

65 - 67

• disease of elderly which has significant implications for treatment

Question 2

What are the risk factors for developing AML?

Answer 2

Congenital genetics

• trisomy 21
• neurofibromatosis
• Fanconi’s anaemia

Environmental

• ionising radiation
• benzene exposure

Treatment related AML

1. topoisomerase II targets - anthracyclines
   - rapidly proliferative disease within 2 years of treatment
   - 11q23 abnormalities
   - good prognosis
2. alkylating agents e.g. Cyclophosphamide
   - 5-6 years after exposure
   - deletions in chromosomes 5 and 7q
   - poor prognosis

Haematological disease - transformation

• MPD
• MDS
• Aplastic anaemia

Question 3

What is the significance of a FLT3 mutation?

Answer 3

mutation in AML causing dysregulation of signal transduction pathways and stimulation of cell proliferation, decreased apoptosis

• associated with a worse prognosis
• relapse rate increased by 2

Question 4

What is the significance of the NPM1 mutation?

Answer 4

improved outcome with chemotherapy in AML

Question 5

What is the conventional treatment regimen for AML?

Answer 5

1. Induction
   - aim to achieve complete remission (neuts > 1, plts > 100, absence of extra medullary leukaemia)
   - Daunorubicin + cytarabine
2. consolidation x 2
   - eliminate residual leukaemia cells
   - Cytarabine

Question 6

What patients with AML would be considered for stem cell transplant?

Answer 6

patients with poor risk factors:

• unfavourable cytogenetics
• intermediate karyotype

must achieve complete remission
- must be medically fit after induction and consolidation

• NOT if NPML1 positive and FLT3 negative (good prognosis)

Question 7

What is the pathognomonic blood film finding in AML?

Answer 7

Auer rods 
(but not all cases of AML have Auer rods)

Blasts

Question 8

What cell surface markers are found on blast cells in AML?

Answer 8

panhaemopoietic cell marker: CD45
stem cell marker: CD34 (not present on all blasts)

myeloid markers: CD 13, 33, 117

monocyte markers: CD 11, 14

Question 9

What are poor prognostic features in AML?

Answer 9

CYTOGENETICS MOST IMPORTANT

• del 7q (cyclophosphamide)
• FLT3 mutation positive
• age > 60
• height of WCC

Question 10

What are good prognostic features in AML?

Answer 10

CYTOGENETICS MOST IMPORTANT

• t(15;17) receptor for retinoid acid = APML
• inversion q16
• NPM1 mutation (if only mutation)
• younger patients

Question 11

What is reduced intensity conditioning?

Answer 11

chemotherapy and RT to reduce tolerance to donor cells

• graft vs tumour effect high
• chronic GVHD
• reduced transplant related mortality

Question 12

What are the blood film findings in APML?

Answer 12

hyper granulated promyelocytes with multiple auer rods

Question 13

What cytogenetic abnormality is present in APML?

Answer 13

t(15;17) - recepto for retinoid acid

Question 14

What is the treatment for APML?

Answer 14

Anthracyclines + ATRA
- All trans retinoid acid
- CR rates of 90%
Arsenic is superior
- 4 year molecular remission = 98%

Question 15

What is ATRA syndrome?

Answer 15

release of cytokines

• decreases sats and ARDs
• treat with Dexamethasone

Question 16

What medical emergency can occur with APML and why?

Answer 16

DIC

- release of myeloperoxidase from promeylocytes causes increased fibrinolysis -> DIC

Question 17

What is the main reason for treatment failure in AML?

Answer 17

drug resistance

Question 18

what are the cell markers in ALL?

Answer 18

CD45 + pan haemopoietic marker
CD34+ stem cell marker (often)

pre-B ALL: early B cell markers: CD 19, CD10
Pre-T ALL: CD3, CD7

Question 19

In what patient group does ALL occur most commonly?

Answer 19

children and adolescents

Question 20

What are some distinguishing features of T cell ALL?

Answer 20

more common in adolescent boys

frequently presents with mediastinal involvement

Question 21

What are poor prognostic factors in ALL?

Answer 21

High WCC
extramedullary disease
- CNS, testis (sanctuary sites)
adults and infants do worse than children and adolescents

CYTOGENETICS MOST IMPORTANT PROGNOSTIC FACTOR

• t(9,22) Philadelphia chromosome
• t(4,11) - infants usually

Question 22

What is the relevance of the philadelphia chromosome in ALL?

Answer 22

poor prognostic factor

indication for Imatinib and allogeneic stem cell transplant

Question 23

What prophylaxis would you give for a patient on chemotherapy for acute leukaemia?

Answer 23

Co-trimoxazole - for PCP prophylaxis

Acyclovir - for VZV prophylaxis

Question 24

What condition should be excluded as a differential for acute leukaemia?

Answer 24

B12 deficiency

- can get blasts and pancytopenia

Question 25

What are the common symptoms of acute leukaemias?

Answer 25

anaemia - lethargy, fatigue, SOB thrombocytopenia - bleeding, bruising leukopenia - infections blasts - increased risk of VTE