Acute and Chronic Leukaemias

Question 1

What are the key investigations in acute leukaemia?

Answer 1

FBE and film
Bone marrow biopsy
Immunophenotyping
Cytogenetics
Molecular studies

Question 2

What is the aim of the investigations in acute leukaemia?

Answer 2

Determine

• Type
• Prognosis
• How best to monitor response to therapy

Question 3

How is acute leukaemia diagnosed?

Answer 3

Infiltration by malignant cells visible on bone marrow biopsy
- Blasts >20% of nucleated cells

Question 4

What are the complications associated with APML management regimes?

Answer 4

Differentiation syndrome = ATRA syndrome
Disseminated intravascular coagulation
Hyperleukocytosis

Question 5

What happens in hyperleukocytosis?

Answer 5

Makes blood very thick, causing

• Renal failure
• Brain complications
• Cardiac complications

Question 6

What is the typical presentation of APML?

Answer 6

Bruising and bleeding due to disseminated intravascular coagulopathy and thrombocytopaenia > medical emergency

Question 7

What features on the blood film or bone marrow aspirate are pathogenic for APML?

Answer 7

Promyelocytes with Auer rods

Question 8

What genetic feature characterises APML?

Answer 8

t(15;17) = PML-RARalpha

Question 9

What is the prognosis of APML?

Answer 9

Curable in >90% of patients

Question 10

What is tumour lysis syndrome?

Answer 10

Group of metabolic abnormalities due to lysis of large number of tumour cells
Everything released from cell

Question 11

What are the paediatric acute lymphocytic leukaemia (ALL) protocols?

Answer 11

For children and young fit adults
Induction chemotherapy with multiple drugs
Prolonged maintenance - ~2 years
Intrathecal chemo prophylaxis
L-asparaginase backbone of therapy
Tyrosine kinase inhibitor
+/- allograft for high risk patients (presence of Philadelphia chromosome)

Question 12

Why is intrathecal chemo prophylaxis used in the paediatric ALL protocol?

Answer 12

ALL often recurs in CNS

IV chemo has poor penetration into CNS

Question 13

What determines prognosis in ALL?

Answer 13

Age - younger better
Response to therapy
Protocol used - paediatric vs adult
Poor prognosis with
- Hypodiploid
- t(4;11)
- t(9;22)
Good prognosis with
- Hyperdiploid

Question 14

What are the B symptoms of cancer?

Answer 14

Weight loss
Night sweats
Loss of appetite

Question 15

What is the Philadelphia chromosome, and what is its gene product?

Answer 15

t(9;22)

BCR-ABL protein

Question 16

Wat is the management of chronic myeloid leukaemia (CML)?

Answer 16

Tyrosine kinase inhibitors

• Selective killing of CML cells > remissions
• Virtually eliminated need for allograft
• In most, no major toxicity

Question 17

What are the three stages in which CML presents?

Answer 17

Chronic
Accelerated
Blast

Question 18

What are the characteristic features of CML?

Answer 18

Leukocytosis with full spectrum of myeloid development
Basophilia
Eosinophilia
t(9;22) and BCR-ABL in all cases
Often hepatosplenomegaly

Question 19

What is the most common adult malignancy?

Answer 19

Chronic lymhoid leukaemia (CLL)

Question 20

What is the typical course of CLL?

Answer 20

Indolent - can be watched for years without treatment

Question 21

What are the molecular features of CLL?

Answer 21

Small mature lymphocytes with expression of

• CD19
• CD5
• CD23

Question 22

What is the management of CLL?

Answer 22

Chemo-immunotherapy with FCR/chlorambucil + rituximab

Patients with high risk genetic have aggressive clinical course and show less sensitivity to therapy