Leukaemia

Question 1

How are leukaemias classified?

Answer 1

Based on lineage:
- myeloid
- lymphoid
Based on developmental stage:
- acute blastic (blast cells)
- chronic cytic (differentiated cells)
Based on anatomical site:
- blood --> leaukaemia
- lymph node with lymphoid malignancy --> lymphoma

Question 2

What is a clone?

Answer 2

Population of cells derived from a single parent cell

Question 3

How do clones differ in normal haematopoesis and malignant haematopoesis?

Answer 3

Normal haematopoesis = polyclonal

Malignant = monoclonal

Question 4

What are the four different types of leukaemia?

Answer 4

Acute lymphoblastic (ALL)
Acute myeloid (AML)
Chronic lymphocytic (CLL)
Chronic myeloid (CML)

Question 5

How are acute leukaemias defined?

Answer 5

Rapidly progressive clonal malignancy of the marrow/blood with maturation defects
–> excess of blasts (>20%) in either peripheral blood or bone marrow

Question 6

Which leukaemia is most common in childhood?

Answer 6

ALL

Question 7

What are the differences in pathology and epidemiology of ALL and AML?

Answer 7

ALL:

• proliferation of lymphocyte progenitors
• most common in children

AML:

• proliferation of granulocyte progenitors
• most common in elderly (>60)

Question 8

Which clinical features are common to both acute leukaemias?

Answer 8

Pancytopenia (anaemia, infection, bleeding)
Bone pain
Organ infiltration:
- hepatosplenomegaly
- lymphadenopathy
- gum hypertrophy
- skin nodules
- mediastinal mass (enlarged thymus)

Question 9

Which additional features may be seen in ALL?

Answer 9

CNS: CN palsy, papilloedema, meningism
Testes: unilateral swelling

Question 10

What would be seen on blood film in acute laeukaemia

Answer 10

Raised blasts with high nuclear:cytoplasmic ratio

• lymphoblasts in ALL
• myeloblasts containing Auer rods in AML

Question 11

How is acute leukaemia diagnosed?

Answer 11

Bone marrow biopsy/aspirate:

• blast cells > 20% confirms diagnosis
• immunophenotyping to identify lineage subtype

Question 12

What is the management for acute leukaemia?

Answer 12

Multi-agent chemotherapy:

• 6-8 months in AML
• up to 3 years in ALL

Question 13

What are the complications of chemotherapy?

Answer 13

Marrow suppression (anaemia, neutropenia, bleeding)
Nausea + vomiting
Hair loss
Liver, renal dysfunction (check LFTs + U&Es first)
Tumour lysis syndrome
Infertility esp. males (sperm bank before)
Cardiomyopathy/HF

Question 14

Why is neutropenia concerning in patients on chemotherapy?

Answer 14

Neutropenic sepsis

–> esp gram -ve bacterial or fungal

Question 15

What is the most common leukaemia in adults?

Answer 15

CLL

Question 16

What causes CLL?

Answer 16

Proliferation of mature B cells

Question 17

How does CLL differ from lymphoma?

Answer 17

Accumulation of B cells in CLL is mainly in the blood and bone marrow
In lymphoma, mainly in lymph nodes

Question 18

What are the clinical features of CLL?

Answer 18

90% asymptomatic at presentation (incidental finding of raised WBCs)
Lymphadenopathy, splenomegaly, hepatomegaly
Symptomatic disease:
- pancytopenia from marrow infiltration
- weight loss, sweats, anorexia
- recurrent infections due to dysfunctional lymphocytes causing low Ig

Question 19

What would be seen on FBC in CLL?

Answer 19

Raised WBC with lymphocytes > 5000
Low platelets
Anaemia (due to marrow failure or DAT+ve haemolytic anaemia)

Question 20

What would be seen on blood film in CLL?

Answer 20

Lymphocytosis

Smudge cells

Question 21

How is CLL staged?

Answer 21

Binet system (A-C)
- based on WBC, Hb + clinical findings

Question 22

What is the management for asymptomatic CLL?

Answer 22

Watchful waiting:

- 3 monthly FBC, flow cytometry + examination

Question 23

What is the management for symptomatic CLL?

Answer 23

Chemotherapy

Question 24

What are some of the complications of CLL?

Answer 24

Recurrent infections (due to treatment or disease)
Richter transformation to high grade Non-Hodgkins lymphoma
Hyperviscosity syndrome

Question 25

Which cells are involved in CML?

Answer 25

Clonal proliferation of myeloid stem cells which differentiate into granulocytes

Question 26

Which mutation is involved in 98% of CML cases?

Answer 26

Philadelphia chromosome encoding p210 tyrosine kinase

Question 27

What are the clinical features of CML?

Answer 27

Often asymptomatic Tired, malaise, fever, weight loss, night sweats Splenomegaly --> LUQ discomfort/early satiety Features of cytopenia Gout/arthralgia (raised urate)

Question 28

What would be seen on FBC and blood film in CML?

Answer 28

Very high WBCs, can be > 100 Anaemia Film: raised granulocytes esp. neutrophils

Question 29

How is CML diagnosed?

Answer 29

Bone marrow biopsy: granulocytic hyperplasia | Cytogenetics (blood or marrow) and FISH for Philadelphia chromosome

Question 30

What is the management for CML?

Answer 30

Imatinab --> inhibits p210 tyrosine kinase and induces long term remission

Question 31

What are the side effects of imatinab?

Answer 31

Cramps Oedema Rash Diarrhoea