Leukaemia

Question 1

t(9;22) Philadelphia chromosome
BCR-ABL fusion gene
Chronic - accelerated - blast crisis phases
Radiation (Hiroshima)
Imatinib

Answer 1

CML

Question 2

3 phases of CML
% blasts
Survival without treatment

Answer 2

Chronic (<5% blasts, 5-6y)
Accelerated (10-19% blasts, 6-12m)
Blast crisis (>20% blasts, 3-6m)

Question 3

Pre-cursor to AML

Answer 3

Myelodysplastic syndrome

Question 4

Mechanism of AML

Answer 4

‘Pre-leukaemic’ Mutation 1 promotes proliferation
‘Leukaemic’ Mutation 2 blocks differentiation
‘Olivia and Isabella’
Two hit hypothesis

Question 5

Down’s syndrome

Answer 5

AML

Question 6

t(8;21)

Answer 6

2nd mutation in 15% AML

RUNX1 mutation

Question 7

Auer rods
Sudan black stain
Gum hypertrophy
CD13, CD33, CD34
Down's syndrome

Answer 7

AML

Question 8

t(15;17)
DIC = acute haemorrhage
EMERGENCY

Answer 8

Acute promyelocytic leukaemia

PML-RARA fusion gene

Question 9

Gum / skin infiltration

Answer 9

Acute monocytic leukaemia

Question 10

Good prognostic indicators AML

Answer 10

t(15;17), t(8;21)

Question 11

Cell affected in ALL

Answer 11

B-cell blast (85%), T-cell blast (15%)

Question 12

Sites most commonly affected in ALL

Answer 12

Bone, testes, CNS, kidneys

Question 13

Good and bad prognostic indicators ALL

Answer 13

Good - hyperdiploidy, t(12;21), t(1;19)

Bad - t(4;11), hypodiploidy

Question 14

Ph chromosome in ALL

Answer 14

Present in 20% (can treat w/ imatinib) - but CML more ass

Question 15

Tx ALL

Answer 15

Supportive + chemo

• CNS directed (tropism for CNS - need high dose / direct CSF injection to cross BBB)
• 1y longer for boys (testes tropism)

Question 16

ALL prognosis

Answer 16

Excellent prognosis in children - 80% 5y disease-free survival
Bad prognosis in adults - 30-40% 5y disease free survival

Question 17

How do you distinguish between AML and ALL?

Answer 17

Myeloblasts vs. lymphoblasts

1. Cytology - M = Auer rods, granules
2. Cytochemistry - M = Myeloperoxidase Sudan Black Stain
3. Immunophenotype
   - Myeloblasts = MPO, CD13/33/14/15)
   - Lymphoblasts = Pre-B (CD19, CD20, TdT, CD10), B (CD19, CD20, surface Ig), T (CD3, CD4, CD8)

Question 18

Crystals formed from granules

Answer 18

Auer Rod (AML)

Question 19

Which lymphoblast?
CD10+
CD20+
CD3+

Answer 19

Pre-B lymphoblast
B lymphoblast
T lymphoblast

Question 20

CD34, CD45, HLA-DR

Answer 20

Myeloblast or lymphoblast

Question 21

MPO, CD13, CD33, CD14, CD15

Auer rod

Answer 21

Myeloblast

Question 22

Elderly man
Smear/ smudge cells
Richter's transformation
Proliferation centres 
Binet + Rai staging

Answer 22

CLL

Question 23

CLL staging

Answer 23

Binet staging (ABC)
Rai staging (I-IV)

Question 24

Binet staging

Answer 24

‘Binet contains B’
A - High WBC + <3 groups of enlarged LNs
B - >3 groups of enlarged LNs
C - signs of BM failure (anaemia or thrombocytopenia)

Question 25

Tx of CLL

Answer 25

Young patients go-go years
Old patients no-go years (only treat if worsens)
p53 mutation = Alemtuzumab; no p53 mutation = Chlorambucil
R-CHOP to prevent DLBC progression
Treat consequences (recurrent infection vaccinate / Abx, AI phenomena immunosuppression)

Question 26

p53 deletion

Answer 26

CLL
Alemtuzumab

(In the presence of a p53 deletion, CLL can be treated with alemtuzumab)

Question 27

Richters transformation

Answer 27

CLL to DLBC

Question 28

Commonest adult leukaemia

Answer 28

CLL

Question 29

On chemo
Tiredness, poluria, polydipsia, abdo pain, vomiting
Hyperkalaemia, high BP, raised phosphate
Dies of cardiac arrest

Answer 29

Tumour lysis syndrome

(Tumour lysis syndrome is a group of metabolic abnormalities that can occur as a complication of cancer treatment. Large numbers of tumour cells are killed off leading to hyperkalaemia, hypocalcaemia, hyperuricaemia high blood nitrogen. It is a bit like rhabdomyolysis. This can result in AKI, seizures, cardiac arrhythmias and ultimately death)

Question 30

Lymphocytosis

Haemolysis, Coomb’s test positive

Answer 30

Evan’s syndrome

CLL with AIHA + ITP