Leukaemia Flashcards

1
Q

Types of Leukaemia?

A

Leukaemia is the name for cancer of a particular line of the stem cells in the bone marrow. This causes unregulated production of certain types of blood cells. They can be classified depending on how rapidly they progress (slow = chronic or fast = acute) and the cell line that is affected (myeloid or lymphoid) to make four main types with different characteristics:

Acute myeloid leukaemia
Acute lymphoblastic leukaemia
Chronic myeloid leukaemia
Chronic lymphocytic leukaemia

There are other rarer and more specialist leukaemias such as acute promyelocytic leukaemia. You are unlikely to come across these in your exams.

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2
Q

Pathophysiology of leukaemia?

A

Leukaemia is a form of cancer of the cells in the bone marrow. A genetic mutation in one of the precursor cells in the bone marrow leads to excessive production of a single type of abnormal white blood cell.

The excessive production of a single type of cell can lead to suppression of the other cell lines causing underproduction of other cell types. This results in a pancytopenia, which is a combination of low red blood cells (anaemia), white blood cells (leukopenia) and platelets (thrombocytopenia).

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3
Q

Ages: leukaemia

A

You can use the mnemonic “ALL CeLLmates have CoMmon AMbitions” to remember the progressive ages of the different leukaemia from 45-75 in steps of 10 years. Remember that ALL (the first in the mnemonic) most commonly affects children under 5 years.

Under 5 and over 45 – acute lymphoblastic leukaemia (ALL)
Over 55 – chronic lymphocytic leukaemia (CeLLmates)
Over 65 – chronic myeloid leukaemia (CoMmon)
Over 75 – acute myeloid leukaemia (AMbitions)

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4
Q

Presentation of Leukaemia?

A

The presentation of leukaemia is quite non-specific. If leukaemia appears on your list of differentials then get an urgent full blood count. Some typical features are:

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

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5
Q

Differential Diagnosis of Petechiae

A

One of the key presenting features of leukaemia is bleeding under the skin leading to bruising and petechiae. This is caused by thrombocytopenia (low platelets). It is important to be aware of the differential diagnoses for this type of non-blanching rash. Don’t ever forget non-accidental injury (abuse) as a differential, particularly in children and vulnerable adults.

Leukaemia
Meningococcal septicaemia
Vasculitis
Henoch-Schonlein Purpura (HSP)
Idiopathic Thrombocytopenia Purpura (ITP)
Non-accidental injury

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6
Q

Diagnosis of leukaemia

A

Full blood count is the initial investigation. NICE recommend a full blood count within 48 hours for patients with suspected leukaemia. Children or young adults with ptechiae or hepatosplenomegaly should be referred immediately to the hospital.

Blood film can be used to look for abnormal cells and inclusions.

Lactate dehydrogenase (LDH) is a blood test that is often raised in leukaemia but is not specific to leukaemia. It can be raised in other cancers and many non-cancerous diseases.

Bone marrow biopsy can be used to analyse the cells in the bone marrow. This is the main investigation for establishing a definitive diagnosis of leukaemia.

Chest xray may show infection or mediastinal lymphadenopathy.

Lymph node biopsy can be used to assess lymph node involvement or investigate for lymphoma.

Lumbar puncture may be used if there is central nervous system involvement.

CT, MRI and PET scans can be used for staging and assessing for lymphoma and other tumours.

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7
Q

Bone Marrow Biopsy: explain the types

A

Bone marrow aspiration involves taking a liquid sample full 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.

Bone marrow biopsy is usually taken from the iliac crest. It involves a local anaesthetic and a specialist needle. Samples from bone marrow aspiration can be examined straight away however a trephine sample requires a few days of preparation.

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8
Q

Acute Lymphoblastic Leukaemia

A

Acute lymphoblastic leukaemia is where there is malignant change in one of the lymphocyte precursor cells. It causes acute proliferation of a single type of lymphocyte, usually B-lymphocytes. Excessive proliferation of these cells causes them to replace the other cell types being created in the bone marrow, leading to a pancytopenia.

This is the most common cancer in children and peaks around 2-4 years. It can also affect adults over 45. It is often associated with Downs syndrome.

Blood film shows blast cells.

It is associated with the Philadelphia chromosome (t(9:22) translocation) in 30% of adults and 3-5% of children with ALL.

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9
Q

Chronic Lymphocytic Leukaemia

A

Chronic lymphocytic leukaemia is where there is chronic proliferation of a single type of well differentiated lymphocyte, usually B-lymphocytes. This usually affects adults over 55 years of age. Often it is asymptomatic but it can present with infections, anaemia, bleeding and weight loss. It can cause warm autoimmune haemolytic anaemia.

CLL can transform into high-grade lymphoma. This is called Richter’s transformation.

Blood film shows “smear” or “smudge” cells. These occur during the process of preparing the blood film where aged or fragile white blood cells rupture and leave a smudge on the film.

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10
Q

Chronic Myeloid Leukaemia

A

Chronic myeloid leukaemia has three typical phases: the chronic phase, the accelerated phase and the blast phase. The chronic phase can last around 5 years, is often asymptomatic and patients are diagnosed incidentally with a raised white cell count.

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

The blast phase follows the accelerated phase and involves an even high proportion of blast cells and blood (>30%). This phase has severe symptoms and pancytopenia. It is often fatal.

The cytogenetic change that is characteristic of CML is the Philadelphia chromosome, which is a translocation of genes between chromosome 9 and 22: it is a t(9:22) translocation.

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11
Q

Acute Myeloid Leukaemia

A

Acute myeloid leukaemia is the most common acute leukaemia in adults. There are many different types of acute myeloid leukaemia all with slightly different cytogenetic differences and differences in presentation.

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.

A blood film will show a high proportion of blast cells. These blast cells can have rods inside their cytoplasm that are named Auer rods.

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12
Q

TOM TIP: There are some key bits of information that you should learn to be able to spot which leukaemia is in the exam:

A

Acute lymphoblastic leukaemia: Most common leukaemia in children. Associated with Down syndrome.

Chronic lymphocytic leukaemia: Most common leukaemia in adults overall. Associated with warm haemolytic anaemia, Richter’s transformation into lymphoma and smudge / smear cells.

Chronic myeloid leukaemia: Has three phases including a 5 year “asymptomatic chronic phase”. Associated with the Philadelphia chromosome.

Acute myeloid leukaemia: Most common acute adult leukaemia. It can be the result of a transformation from a myeloproliferative disorder. Associated with Auer rods.

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13
Q

Management of leukaemia

A

Treatment will be coordinated by an oncology multi-disciplinary team. Leukaemia is primarily treated with chemotherapy and steroids.

Other therapies include:

Radiotherapy
Bone marrow transplant
Surgery

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14
Q

Complications of Chemotherapy

A

Failure
Stunted growth and development in children
Infections due to immunodeficiency
Neurotoxicity
Infertility
Secondary malignancy
Cardiotoxicity
Tumour lysis syndrome

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15
Q

Tumour Lysis Syndrome

A

Tumour lysis syndrome is caused by the release of uric acid from cells that are being destroyed by chemotherapy. The uric acid can form crystals in the interstitial tissue and tubules of the kidneys and causes acute kidney injury. Allopurinol or rasburicase are used to reduce the high uric acid levels. Other chemicals such as potassium and phosphate are also released so these need to be monitored and treated appropriately. High phosphate can lead to low calcium, which can have an adverse effect, so calcium is also monitored.

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