Malignant Haematology and Acute Leukaemia

Question 1

What are the kinetics of normal haemopoiesis?

Answer 1

Self-renewal
Proliferation
Differentiation or lineage commitment
Maturation
Apoptosis

Question 2

What enzyme is expressed on neutrophils?

Answer 2

Myeloeroxidase

Question 3

How can we identify normal, more mature cells?

Answer 3

Morphology
Cell surface antigens (e.g. glycophorin A=red cells)
Enzyme expression

Question 4

How can we identify normal progenitors/stem cells?

Answer 4

Cell surface antigens
Cell culture assays
Animal models (not routine)

Question 5

What is malignant haemopoiesis characterised by?

Answer 5

Increased numbers of often dysfunctional cells and may have loss of the normal haemopoietic reserve
One or more of: increased proliferation, lack of differentiation/maturation/apoptosis

Question 6

What causes haematological malignancies?

Answer 6

Genetics, epigenetic, environmental interaction
Somatic mutations in regulatory genes (driver/passenger mutations)
Multiple ‘hits’ or single event
Recurrent cytogenetic abnormalities (not causal in most, but contributory)

Question 7

What do driver mutations do on the cells carrying them?

Answer 7

Confer growth advantage and have been +vely selected during the evolution of the cancer

Question 8

What do passenger mutations do on the cells carrying them?

Answer 8

Do not confer growth advantage, but happened to be present in an ancestor of the cancer cell when it acquired one of its drivers

Question 9

What can somatic mutations observed in 10% of persons older than 65 without a blood disorder predict?

Answer 9

Subsequent risk of haem malignancy

Question 10

What is a clone?

Answer 10

Population of cells derived from a single parent cell
Parent cell has a genetic marker (driver or chromosomal change shared by daughter cells
However clonal diversity is possible

Question 11

Is normal haemopoiesis poly or monoclonal?

Answer 11

Poly, malignancy haemopoiesis is usually mono

Question 12

How are haematological malignancies classified?

Answer 12

Speed of presentation- acute or chronic, usually depends on type and stage of defect
Site- medullary (marrow)/extramedullary, blood (leukaemia)/LN (lymphoma)
Lineage- myeloid/lymphoid

Question 13

What are the types of leukaemias?

Answer 13

Acute Myeloid Leukaemia
Acute Lymphoblastic Leukaemia
Chronic Myeloid Leukaemia
Chronic Lymphocytic Leukaemia

Question 14

What are the types of lymphomas?

Answer 14

High grade and low grade

Question 15

What can CLL involve?

Answer 15

Both blood/bone marrow and lymph nodes

Question 16

What is myeloma?

Answer 16

Plasma cell malignancy in marrow

Question 17

Describe acute leukaemia

Answer 17

Rapidly progressive clonal malignancy of the marrow/blood with maturation defect(s)
Decrease/loss of normal haemopoietic reserve

Question 18

What is acute leukaemia defined as?

Answer 18

Excess of ‘blasts’ (≥20%)in either the peripheral blood or bone marrow

Question 19

What is ALL?

Answer 19

Malignancy disease of lymphocytes

Most common childhood cancer (30/40 cases per million)

Question 20

What is the presentation of ALL?

Answer 20

Due to marrow failure (naemia, infections, bleeding)
Leukaemic effects: high WCC and involvement of extra-medullary areas e.g. CNS, lymph nodes sometimes causing venous obstruction
Bone pain

Question 21

Describe AML

Answer 21

More common in the elderly (>60 years)
May be ‘de novo’ or secondary
Presentation can be similar to ALL (marrow failure)
Subgroups of AML may have characteristic presentation- DIC, gum infiltration

Question 22

What are the Ix for acute leukaemia?

Answer 22

Blood count and film
Coag screen
Bone marrow aspirate (morphology, immunophenotype by flow cytometry, cytogenetics- diagnostic utility/prognostic significance, trephine (piece of bone)- enables better assessment of cellularity and helpful when aspirate is sub-optimal)

Question 23

What will be seen on the blood film in acute leukaemia?

Answer 23

Reduction in normal cells
Presence of abnormal cells
Blasts with high nuclear:cytoplasmic ratio

Question 24

What is required for a definitive diagnosis between AML and ALL?

Answer 24

Immunophenotyping- as they will express different lineage associated proteins

Question 25

What is the treatment for ALL?

Answer 25

Multi agent chemo- Hickman line Can last up to 2-3 years Different phases of treatment of varying intensity (induction, consolidation, intensification, maintenance) Targeted treatments in certain subsets

Question 26

What is the treatment for AML?

Answer 26

Multi agent chemo-Hickman line Normally intensive Between 2-4 cycles of chemotherapy (5-10 days of chemotherapy followed by 2-4 weeks of recovery) Prolonged hospitalisation

Question 27

What are the problems with marrow suppression?

Answer 27

Anaemia Neutropenia- infections (G-ve bacteria can cause fulminant life threatening sepsis) Thrombocytopenia- bleeding (purpura, petechiae when PTL <20)

Question 28

What are the complications of chemo?

Answer 28

Nausea and vomiting Hair loss Liver, renal dysfunction Tumour lysis syndrome (during first course of treatment) Infection -Bacterial: empirical treatment with broad spectrum antibiotics (particularly covering Gram negative organisms) as soon as neutropenic fever -Fungal (if prolonged neutropenia and persisting fever unresponsive to anti-bacterial agents) -Protozoal e.g PJP (more relevant in ALL therapy) Late- loss of fertility, cardiomyopathy with anthracyclines

Question 29

Will many AML/ALL patients go into remission?

Answer 29

Yes- <5% marrow blasts with recovery of normal haemopoiesis | Many will also relapse

Question 30

What is the cure rate for ALL?

Answer 30

Childhood >85-90% (depending on bio-markers) | Adult ~30-40%

Question 31

What is the cure rate for AML?

Answer 31

Adult <60yo 40-50% (depending on bio markers) | >60yo ~10% or less

Question 32

What can be potentially curative in a minority of patients, and can be used in some after initial therapy or at relapse?

Answer 32

Allogenic stem cell transplantation