Acute Leukaemia

Question 1

Who do ALL and AML usually occur in?

Answer 1

ALL: young
AML: elderly

Question 2

What triad does bone marrow failure present as?

Answer 2

Anaemia
Thrombocytopoenia
Neutropoenia

Question 3

Summarise aetiology of acute leukaemia

Answer 3

Acute uncontrolled proliferation of immature blast cells
This interfered with development and function of healthy WBC/RBC/platelets
- loss of ability to differentiate > stuck in blast stage, don’t function
- uncontrollable division > crowding out of healthy cells

Question 4

What kinds of abnormalities trigger AML?

Answer 4

Chromosome abnormality (recurrent) 
Or 
Molecular changes (with apparently normal chromosomes)

Question 5

What types of chromosome abnormalities occur in AML?

Answer 5

Duplication (usually trisomy, e.g. 21)
Loss 
Translocation (e.g. APML - t(15,17))
Inversion
Deletion

Question 6

What are RF to get AML?

Answer 6

Familial
Irradiation
Anticancer drugs
Cigarette smoking

Question 7

What does leukaemia development require for AML?

Answer 7

At least 2 hits

Question 8

What are type 1 and type 2 abnormalities in AML?

Answer 8

• Type 1 abnormality: promote proliferation and survival (anti-apoptosis)
• Type 2 abnormality: blocks differentiation, leading to accumulation of blast cells

Question 9

What mutations can occur. on the core binding factor?

Answer 9

TRANSLOCATION: t(8,21)
fuses RUNX1 with RUNZ1T1
Causes AML

INVERSION of Chr 16
fuses CBF beta to MYH11

Question 10

What is the translocation of APML?

Answer 10

t(15,17)

Question 11

What occurs in APML?

Answer 11

Excess of abnormal promyelocytes

Question 12

What abnormal genes can t(15,17) form?

Answer 12

Type 1: FLT2-ITD

Type 2: PML-RARA

Question 13

What structures are abnormal within promyelocytes in APML?

Answer 13

AUER RODS

Question 14

How can you differentiate AML from ALL

Answer 14

Cytological:
- AML: Auer rods, fine speckled granules

Cytochemistry: (all +ve for AML, -ve for ALL)

• myeloperoxidase
• Sudan black
• non-specific esterase

Immunophenotyping

• flow cytometry
• immunohistochemistry
• immunocytochemistry

Question 15

What clinical presentations occur following local infiltration?

Answer 15

splenomeg
hepatomeg
gum infiltration
lymphadenopathy

Question 16

How can you diagnose AML?

Answer 16

Blood film (Auer rods, granules)
Immunophenotyping 
Bone Marrow aspirate 
Cytogenetic studies
Molecular studying

Question 17

What is treatment of AML

Answer 17

Supportive care (RBC, platelets, FFP/cryoprecipitate, antibiotics, long line, allopurinol)

Chemotherapy

Transplanted molecular therapy

transplantation

Question 18

Why is combination chemo always used in AML?

Answer 18

Different MOAs
Synergy
Non-overlapping toxicity

Question 19

What are important clinical features of ALL?

Answer 19

• Bone marrow failure triad
• Local infiltration (lymphadenopathy, thymic enlargement, splenomegaly, hepatomegaly, testes/CNS/kidney invasion, bone pain)

Question 20

What are the 2 possible sources of ALL?

Answer 20

T cells

B cells

Question 21

What type of ALL can you treat with TK inhibitors?

Answer 21

Philadelphia chromosome

t(9,22)

Question 22

Name one TKinhibitor?

Answer 22

Imatinib

Question 23

What are specific therapies for ALL?

Answer 23

Systemic chemo
CNS directed therapy
molecular targeted tx
transplantation

Question 24

How long do you give systemic chemo for in ALL?

Answer 24

2-3 years

Question 25

How does chemo change for boys compared girls in ALL?

Answer 25

Give boys chemo for longer

Because the testes are a site of accumulation for lymphoblasts

Question 26

Why do you give CNS directed therapy in ALL?

Answer 26

To prevent development of long term CNS disease

Question 27

What is prognosis for ALL like depending on age group?

Answer 27

VERY GOOD if CHILDREN

BAD if ADULT