Leukaemia

Question 1

What is leukaemia?

Answer 1

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 are the different leukaemias classified?

Answer 2

Depending on how rapidly they progress: acute or chronic, and the cell line that is affected: myeloid or lymphoid.

Question 3

What are the 4 main types of leukaemias?

Answer 3

1. Acute myeloid leukaemia - rapidly progressing cancer of the myeloid cell line.
2. Acute lymphoblastic leukaemia - rapidly progressing cancer of the lymphoid cell line.
3. Chronic myeloid leukaemia - slowly progressing cancer of the myeloid cell line.
4. Chronic lymphocytic leukaemia - slowly progressing cancer of the lymphoid cell line.

Question 4

What is another rarer type of leukaemia?

Answer 4

Acute promyelocytic leukaemia.

Question 5

What age do most leukaemias affect?

Answer 5

60-70s.

Question 6

Which leukaemia commonly affects children under 5?

Answer 6

Acute lymphoblastic leukaemia.

Question 7

What are the key differentiating features between the different leukaemias?

Answer 7

1. ALL is the most common leukaemia in children and is associated with down syndrome.
2. CLL is associated with warm haemolytic anaemia, Richter’s transformation and smudge cells
3. CML has 3 phases including a long chronic phase & is associated with the Philadelphia chromosome.
4. AML may result in a transformation from a myeloproliferative disorder and is associated with Auer rods.

Question 8

What is the pathophysiology of leukaemia?

Answer 8

A genetic mutation in one of the precursor cells in the bone marrow leads to excessive production of a single type of abnormal WBC. The excessive production of a single type of cell can suppress the other cell lines, causing the underproduction of different cell types, resulting in pancytopenia (anaemia, leukopenia and thrombocytopenia).

Question 9

How does leukaemia present?

Answer 9

Non-specific symptoms such as fatigue, fever, pallor due to anaemia, petechiae or bruising due to thrombocytopenia, abnormal bleeding, lymphadenopathy, hepatosplenomegaly, and failure to thrive in children.

Question 10

What does bleeding under the skin cause and what are these called based on the size of the lesions?

Answer 10

Bleeding under the skin causes non-blanching lesions.
- Petechiae = less than 3mm and caused by burst capillaries
- purpura = 3-10mm
- ecchymosis = larger than 1cm.

Question 11

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

Answer 11

Leukaemia, meningococcal septicaemia, vasculitis, HSP, ITP, thrombotic thrombocytopenic purpura, traumatic or mechanical (e.g., severe vomiting), NAI.

Question 12

When leukaemia is suspected what is urgently needed?

Answer 12

Urgent FBC within 48 hours.

Question 13

When are children or young people sent for immediate specialist assessment?

Answer 13

If they have petechiae or hepatosplenomegaly.

Question 14

What investigations are carried out for a diagnosis?

Answer 14

• FBC
• blood film: look for abnormal cells and inclusions
• LDH: non specific marker of tissue damage. It’s often raised in leukaemia but also in other cancers and many non-cancerous conditions, including heavy exercise. Not helpful as a screening test but may be used for specialist assessment and monitoring
• Bone marrow biopsy: used to analyse the cells in the bone marrow to establish a definitive diagnosis of leukaemia
• CT and PET scans to help staging
• lymph node biopsy to assess abnormal lymph nodes
• genetic tests (looking at chromosomes and DNA changes) & immunophenotyping (looking for specific proteins on the surface of the cells) may be performed to help guid treatment and prognosis

Question 15

Where is a bone marrow biopsy taken from?

Answer 15

Usually from the iliac crest.

Question 16

What does a bone marrow biopsy involve and what are the different options?

Answer 16

Local anaesthetic and specialist needle. The options are aspiration or trephine.

Question 17

What does bone marrow aspiration involve?

Answer 17

Taking a liquid sample of cells from within the bone marrow.

Question 18

What does bone marrow trephine involve?

Answer 18

Taking a solid core sample of the bone marrow, providing a better assessment of the cells and structure.

Question 19

What does acute lymphoblastic leukaemia affect and therefore cause?

Answer 19

• one of the lymphocyte precursor cells
• causing acute proliferation of a single type of lymphocyte, usually B lymphocytes
• excessive accumulation of these cells replaces the other cell types in the bone marrow, leading to pancytopenia

Question 20

Who does acute lymphoblastic leukaemia affect and who is it more common in?

Answer 20

Children under 5 but can also affect adults, more common with Down’s syndrome.

Question 21

What can acute lymphoblastic leukaemia be associated with?

Answer 21

The Philadelphia chromosome (but this is more associated with CML).

Question 22

What is chronic lymphocytic leukaemia (CLL)?

Answer 22

Where there is slow proliferation of a single type of well-differentiated lymphocyte, usually B lymphocytes.

Question 23

Who does chronic lymphocytic leukaemia affect?

Answer 23

Usually adults over 60 years.

Question 24

How does chronic lymphocytic leukaemia present?

Answer 24

Usually asymptomatic, but can present with infections, anaemia, bleeding, and weight loss.

Question 25

What can chronic lymphocytic leukaemia cause?

Answer 25

Warm autoimmune haemolytic anaemia.

Question 26

What is Richter's transformation?

Answer 26

- the rare transformation of **CLL into high grade B cell lymphoma** - occurs when leukaemia cells enter the lymph node and change into high grade, fast growing non-hodgkin’s lymphoma - patients often become unwell very suddenly: **fever, night sweats, nausea** (they won’t have infective symptoms such as vomiting, diarrhoea, cough, headache) - Richter’s transformation usually **occurs 2-6 years after a diagnosis of CLL**

Question 27

What are smear/smudge cells and what are they associated with?

Answer 27

They're ruptured WBCs that occur while preparing the blood film when the cells are aged or fragile, associated with CLL.

Question 28

What are the 3 phases of chronic myeloid leukaemia (CML)?

Answer 28

Chronic phase, accelerated phase, blast phase.

Question 29

How does chronic myeloid leukaemia present?

Answer 29

Usually presents in patients older than 60 with progressive anaemia, weight loss, night sweats, splenomegaly, and a sense of fullness.

Question 30

What do blood results show in chronic myeloid leukaemia?

Answer 30

Increase in granulocytes at different stages of maturation +/- thrombocytosis (increased platelets).

Question 31

What is the chronic phase of chronic myeloid leukaemia?

Answer 31

Usually asymptomatic, diagnosed after incidental finding of a raised WCC, can last several years before progressing.

Question 32

When does the accelerated phase of chronic myeloid leukaemia occur?

Answer 32

When the abnormal blast cells take up a high proportion of the bone marrow and blood cells, leading to more symptoms.

Question 33

When does the blast phase of chronic myeloid leukaemia occur and what does it involve?

Answer 33

It follows the accelerated phase, involving a **higher proportion (over 20%) of blast cells** in the blood, severe symptoms, and **pancytopenia**.

Question 34

What is chronic myeloid leukaemia particularly associated with?

Answer 34

The Philadelphia chromosome, an abnormal chromosome 22 caused by a reciprocal translocation between chromosome 9 and chromosome 22.

Question 35

What is the treatment choice for chronic myeloid leukaemia?

Answer 35

Imatinib - tyrosine kinase inhibitor.

Question 36

When does acute myeloid leukaemia (AML) present?

Answer 36

Can present at any age, but normally presents from middle age onwards.

Question 37

What can acute myeloid leukaemia be a result of?

Answer 37

It can be the result of a **transformation** from a **myeloproliferative disorder such as polycythaemia rubra vera or myelofibrosis**

Question 38

What will investigations show in acute myeloid leukaemia?

Answer 38

Blood film and bone marrow biopsy will show a high proportion of blast cells, with Auer rods in the cytoplasm of blast cells.

Question 39

How is leukaemia mainly treated?

Answer 39

Chemotherapy and targeted therapies, depending on the type and individual features.

Question 40

What are some examples of targeted therapies and which leukaemia are they mainly used in?

Answer 40

Mainly used in CLL: tyrosine kinase inhibitors (e.g., ibrutinib) and monoclonal antibodies (e.g., rituximab, which targets B cells).

Question 41

What are some other treatment options for leukaemia?

Answer 41

Radiotherapy, bone marrow transplant, and surgery.

Question 42

What are some complications of chemotherapy?

Answer 42

- 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 43

What is tumour lysis syndrome?

Answer 43

Results from chemicals released when cells are destroyed by chemotherapy.

Question 44

What does tumour lysis syndrome result in?

Answer 44

High uric acid, high potassium, high phosphate, and low calcium (as a result of high phosphate).

Question 45

What can uric acid form and therefore lead to?

Answer 45

Can form crystals in the interstitial space and tubules of the kidneys, causing AKI.

Question 46

What can be used to suppress uric acid levels?

Answer 46

Allopurinol and rasburicase.

Question 47

What can hyperkalaemia lead to?

Answer 47

Can cause cardiac arrhythmias.

Question 48

What does the release of cytokines lead to?

Answer 48

Systemic inflammation.

Question 49

For patients at risk of tumour lysis syndrome, what is needed?

Answer 49

Very good hydration and urine output prior to chemotherapy.