Leukaemia (zero to finals)

Question 1

What is leukaemia?

Answer 1

Leukaemia is cancer of a particular line of stem cells in the bone marrow, causing unregulated production of a specific type of blood cell.

Question 2

How many leaukaemia types are there?

Answer 2

4 types

Question 3

How are the leukaemia types classified?

Answer 3

Classified depending on how rapidly they progress (chronic is slow and acute is fast) and the cell line that is affected (myeloid or lymphoid)

Question 4

What is AML?

Answer 4

Acute myeloid leukaemia (rapidly progressing cancer of the myeloid cell line)

AML may result in a transformation from a myeloproliferative disorder and is associated with Auer rods

Question 5

What is ALL?

Answer 5

Acute lymphoblastic leukaemia (rapidly progressing cancer of the lymphoid cell line)

ALL is the most common leukaemia in children and is associated with Down syndrome

Question 6

What is CML?

Answer 6

Chronic myeloid leukaemia (slowly progressing cancer of the myeloid cell line)

CML has three phases, including a long chronic phase, and is associated with the Philadelphia chromosome

Question 7

What is CLL?

Answer 7

Chronic lymphocytic leukaemia (slowly progressing cancer of the lymphoid cell line)

CLL is associated with warm haemolytic anaemia, Richter’s transformation and smudge cells

Question 8

What is richter’s transformation?

Answer 8

The occurrence of an aggressive lymphoma in patients with a previous or concomitant diagnosis of chronic lymphocytic leukemia (CLL)

Question 9

What are smudge cells?

Answer 9

Remnants of cells that lack any identifiable cytoplasmic membrane or nuclear structure.

Smudge cells, also called basket cells, are most often associated with abnormally fragile lymphocytes in disorders such as chronic lymphocytic leukemia (CLL).

Question 10

What is the typical age range for leukaemia?

Answer 10

Most types of leukaemia occur in patients over 60-70.

The exception is acute lymphoblastic leukaemia, which most commonly affects children under five years.

Question 11

Leakaemia presentation is usually non-specific. What are the potential presenting features?

Answer 11

Fatigue
Fever
Pallor due to anaemia
Petechiae or bruising due to thrombocytopenia
Abnormal bleeding
Lymphadenopathy
Hepatosplenomegaly
Failure to thrive (children)

Question 12

What is one key presenting feature of leukaemia?

Answer 12

Bleeding under the skin due to thrombocytopenia.

Bleeding under the skin causes non-blanching lesions.

Question 13

How are the non-blanching lesions categorised in leukaemia?

Answer 13

These lesions are called different things based on the size of the lesions:

Petechiae are less than 3 and caused by burst capillaries
Purpura are 3 – 10mm
Ecchymosis is larger than 1cm

Question 14

What is a non-blanching rash?

Answer 14

Non-blanching rashes are rashes which do not disappear with pressure, particularly using the ‘glass test’.

Question 15

What are the main differentials for a non-blanching rash caused by bleeding under the skin?

Answer 15

Leukaemia
Meningococcal septicaemia
Vasculitis
Henoch-Schönlein purpura (HSP)
Immune thrombocytopenic purpura (ITP)
Thrombotic thrombocytopenic purpura (TTP)
Traumatic or mechanical (e.g., severe vomiting)
Non-accidental injury

Question 16

For suspected leukaemia, when should a full blood count be done?

Answer 16

Within 48 hours for patients with suspected leukaemia.

A full blood count is the initial investigation.

Question 17

What is a blood film used for in leukaemia?

Answer 17

A blood film is used to look for abnormal cells and inclusions.

Question 18

Where is a bone marrow biopsy usually taken from?

Answer 18

Bone marrow biopsy is usually taken from the iliac crest. It involves a local anaesthetic and a specialist needle.

Question 19

What are the 2 main options for a bone marrow biopsy?

Answer 19

The options are aspiration or trephine.

Bone marrow aspiration involves taking a liquid sample of cells from within the bone marrow.

Bone marrow trephine involves taking a solid core sample of the bone marrow and provides a better assessment of the cells and structure.

Question 20

What cell type is usually affected in ALL?

Answer 20

Affects one of the lymphocyte precursor cells, causing acute proliferation of a single type of lymphocyte, usually B-lymphocytes.

This replaces all other cells in the bone marrow leading to pancytopenia (overall low blood cells).

Question 21

Who is commonly affected with ALL?

Answer 21

ALL most often affects children under five but can also affect older adults. It is more common with Down’s syndrome.

Can be associated with philadelphia chromosome (but it is more associated with CML)

Question 22

What cell type is affected in CLL?

Answer 22

Chronic lymphocytic leukaemia is where there is slow proliferation of a single type of well-differentiated lymphocyte, usually B-lymphocytes.

It usually affects adults over 60 years of age.

Question 23

CLL usually presents with symptoms. True/false?

Answer 23

False

Usually asymptomatic.

But can present with infections, anaemia, bleeding and weight loss.

Question 24

What type of anaemia can CLL cause?

Answer 24

Warm autoimmune haemolytic anaemia

Question 25

What is Richter's transformation in CLL?

Answer 25

Refers to the rare transformation of CLL into high-grade B-cell lymphoma.

Question 26

What are smudge/smear cells in CLL?

Answer 26

Ruptured white blood cells that occur while preparing the blood film when the cells are aged or fragile. They are particularly associated with chronic lymphocytic leukaemia.

Question 27

What are the 3 phases of CML?

Answer 27

Chronic phase Accelerated phase Blast phase

Question 28

What is the chronic phase of CML?

Answer 28

The chronic phase is often asymptomatic, and patients are diagnosed after an incidental finding of a raised white cell count. This phase can last several years before progressing.

Question 29

What is the accelerated phase of CML?

Answer 29

The accelerated phase occurs when the abnormal blast cells take up a high proportion (10-20%) of the bone marrow and blood cells. In the accelerated phase, patients are more symptomatic and develop anaemia, thrombocytopenia and immunodeficiency.

Question 30

What is the blast phase of CML?

Answer 30

The blast phase follows the accelerated phase and involves an even higher proportion (over 20%) of blast cells in the blood. The blast phase has severe symptoms and pancytopenia and is often fatal.

Question 31

What chromosome is CML associated with?

Answer 31

"Philadelphia" chromosome This refers to an abnormal chromosome 22 caused by a reciprocal translocation (swap) of genetic material between a section of chromosome 9 and chromosome 22.

Question 32

In CML, what does the translocation of chromosomes 9 and 22 cause?

Answer 32

This translocation creates an abnormal gene sequence called BCR-ABL1, which codes for an abnormal tyrosine kinase enzyme that drives the proliferation of the abnormal cells.

Question 33

What are characteristic features of AML?

Answer 33

A blood film and bone marrow biopsy will show a high proportion of blast cells. Auer rods in the cytoplasm of blast cells are a characteristic finding in AML.

Question 34

What ages are usually affected by AML and how can it occur?

Answer 34

It can present at any age but normally presents from middle age onwards. It can be the result of a transformation from a myeloproliferative disorder, such as polycythaemia ruby vera or myelofibrosis.

Question 35

How is leukaemia typically treated?

Answer 35

Leukaemia is mainly treated with chemotherapy and targeted therapies, depending on the type and individual features.

Question 36

What are some examples of targeted therapies for leukaemia?

Answer 36

Examples of targeted therapies include (mainly used in CLL): Tyrosine kinase inhibitors (e.g., ibrutinib) Monoclonal antibodies (e.g., rituximab, which targets B-cells)

Question 37

What are some side effects of chemotherapy?

Answer 37

Failure to treat cancer Stunted growth and development in children Infections due to immunosuppression Neurotoxicity Infertility Secondary malignancy Cardiotoxicity (heart damage) Tumour lysis syndrome

Question 38

How does tumour lysis syndrome occur?

Answer 38

Tumour lysis syndrome results from chemicals released when cells are destroyed by chemotherapy

Question 39

Features of tumour lysis syndrome?

Answer 39

High uric acid High potassium (hyperkalaemia) High phosphate Low calcium (as a result of high phosphate)

Question 40

What can tumour lysis syndrome lead to?

Answer 40

Uric acid can form crystals in the interstitial space and tubules of the kidneys, causing acute kidney injury. Hyperkalaemia can cause cardiac arrhythmias. The release of cytokines can cause systemic inflammation.

Question 41

What can be used to reduce the risk of tumour lysis syndrome prior to chemotherapy?

Answer 41

Very good hydration and urine output before chemotherapy is required in patients at risk of tumour lysis syndrome. Allopurinol or rasburicase may be used to suppress the uric acid levels.