Leukaemia is a very common exam topic and one that many candidates struggle to get to grips with. This article is not intended to be an all-encompassing review of this complex and highly-specialised topic but should provide you with the knowledge needed to approach the common questions that occur in medical exams.

Leukaemia is a group of malignancies of the bone marrow that interfere with the normal production of blood cells. Malignant cells gradually replace normal bone marrow and can spill over into the peripheral circulation.

Overall, leukaemia is most common in the elderly, with 60% of cases occurring in patients aged over 50 years. It is, however, the most common malignancy of childhood, with an incidence of 3.5 per 100,00 per years in children under 15 years.


Acute and chronic leukaemias

Leukaemia can be either acute or chronic. The acute leukaemias are:

  • Acute myeloid leukaemia
  • Acute lymphoblastic leukaemia


The chronic leukaemias are:

  • Chronic myeloid leukaemia
  • Chronic lymphocytic leukaemia


The main differences between acute and chronic leukaemias are summarised in the table below:


Acute leukaemiasShow rapid proliferation of relatively undifferentiated malignant cells.
Are characterised by the development of bone marrow failure with consequent anaemia, neutropenia and thrombocytopenia.
Are the most common leukaemias in children.
Chronic leukaemiasFollow a relatively prolonged natural history.
Are characterised by an excess of more mature, differentiated malignant cells in the marrow and blood.
Compromise marrow function n in the later stages
Have features related to the high load of malignant cells, e.g. hepatosplenomegaly
Are rarely seen in children.


Acute myeloid leukaemia

Acute myeloid leukaemia (AML) predominantly affects adults and is commonest between ages 65 and 70.

It typically presents with clinical features secondary to leukaemic infiltration of bone marrow and extramedullary sites:

  • Anaemia (lethargy, pallor and breathlessness)
  • Thrombocytopaenia (petechiae, bruising, epistaxis, haemorrhage)
  • Neutropenia (infections)
  • Hepatosplenomegaly
  • Gingival infiltration
  • Leukaemia cutis (infiltration of neoplastic leukocytes in the skin, occurs in around 10% of patients)
  • Central nervous system involvement is very rare


Typically, the full blood count in patients with AML has the following features:

  • Anaemia
  • Leukopenia or leukocytosis can be present
  • Thrombocytopaenia


Other commonly encountered laboratory findings include:

  • Raised lactate dehydrogenase (LDH) levels
  • Raised uric acid secondary to rapid cell turnover
  • Clotting screen – DIC is common


The diagnostic test of choice is bone marrow aspiration. A peripheral blood blast count of greater than 20% is required to make a diagnosis of AML. Cytochemical staining allows classification into different subtypes M0 to M7.

Treatment should be coordinated by a specialised centre and is frequently trial-based. A number of different chemotherapeutic agents and regimens are currently in use.


Acute lymphoblastic leukaemia (ALL)

Acute lymphoblastic leukaemia (ALL)predominantly affects children and is the most common cancer of childhood. The peak age of incidence is between 2 and 4 years of age, and ALL is rare in adulthood.

There are a number of recognised risk factors, including the following:

  • Familial predisposition (25% concordance in monozygotic twins)
  • Trisomy 21 (Down’s syndrome)
  • Exposure to high doses of radiation


The clinical features of ALL are variable, but many children present with an acute illness that can mimic coryza or viral illness. Other features of ALL include:

  • Generalised weakness and lethargy
  • Non-specific muscle, joint and bone pain
  • Anaemia
  • Unexplained bruising and petechiae
  • Oedema
  • Lymphadenopathy
  • Hepatosplenomegaly
  • CNS involvement in ALL is common


Typically, the full blood count in patients with ALL has the following features:

  • Anaemia (normocytic or macrocytic)
  • Leukopenia in around 50% (WCC < 10x 109/l)
  • Leukocytosis in around 60% (WCC > 10 x 109/l)
  • Hyperleukocytosis in around 25% (WCC > 50 x 109/l)
  • Thrombocytopaenia


Other commonly encountered laboratory findings include:

  • Raised lactate dehydrogenase (LDH) levels
  • Raised uric acid secondary to rapid cell turnover
  • Clotting screen – DIC can occur, but less commonly than with AML


As with AML, the diagnostic test of choice is bone marrow aspiration. A bone marrow and/or peripheral blood blast count of greater than 20% is required to make a diagnosis.

ALL is classified using the French-American-British (FAB) classification into 3 groups:

  • ALL-L1: small uniform cells
  • ALL-L2: large varied cells
  • ALL-L3: large varied cells with vacuoles


As with AML, treatment is with chemotherapy, and a number of different agents and regimens are in use. The cure rate is approximately 80% in children, and 50% in adults.


Chronic myeloid leukaemia

Chronic myeloid leukaemia (CML) occurs predominantly in adults of middle age and the elderly. It accounts for 20% of all leukaemias. Over 90% of cases of CML have the Philadelphia chromosome. The Philadelphia chromosome is a balanced translocation between chromosomes 9 and 22.

CML tends to develop insidiously over the course of several years. This is referred to as the ‘chronic stage’. This is generally asymptomatic, and 90% of patients are diagnosed during this stage, with it often being discovered as a result of a routine blood test. There are fewer than 10% immature white cells (blasts) in the bone marrow during this stage.

Symptoms tend to start appearing when expansion of CML cells occurs. This is referred to as the ‘accelerated stage’. Approximately 10% are diagnosed during this stage. Between 10 and 30% of blood cells in the bone marrow are blasts during this stage. Common clinical features during this stage include:

  • Tiredness and fatigue
  • Fever and night sweats
  • Abdominal distension
  • Left upper quadrant pain (splenic infarction)
  • Splenomegaly (most common examination finding)
  • Hepatomegaly
  • Easy bruising
  • Gout (rapid cell turnover)
  • Hyperviscosity (CVA, priapism)


A small number of patients present with a ‘blast crisis’ (blast stage). During this stage, more than 30% of the blood cells in the bone marrow are immature blast cells. Patients presenting in this stage are generally very unwell with severe constitutional symptoms (fever, weight loss, bone pain), infections and bleeding diathesis.

Eventually, almost all patients with CML transform to blast crisis, although this can take as long as 10 years to occur. A blast crisis is diagnosed if any of the following features are present in a patient with CML:

  • > 20% myeloblasts or lymphoblasts in the blood or bone marrow
  • Large clusters of blasts found on bone marrow biopsy
  • The presence of a chloroma (a solid tumour comprised of myeloblasts that occurs outside of the bone marrow)


Laboratory findings in CML include:

  • Markedly elevated white cell count (often greater than 100x 109/l)
  • Left shift with increased number of immature leukocytes
  • Mild-moderate normochromic, normocytic anaemia
  • Platelets can be low, normal or elevated
  • Philadelphia chromosome present in > 80%
  • Serum uric acid and ALP often elevated


Tyrosine kinase inhibitors (TKIs), such as imatinib and dasatinib, form the current mainstay of treatment of CML. Allogenic bone marrow transplantation is now reserved for cases that have failed to respond to TKIs.


Chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia (CLL) is the most common type of adult leukaemia. It arises as a consequence of clonal proliferation of relatively mature lymphocytes. Approximately 95% of cases are of B-cell lineage. It is predominantly a disease of adult men with >75% of patients that present with CLL are men over the age of 50.

It is the most indolent of the chronic leukaemia and is often discovered as an incidental finding when blood counts are performed for other reasons, such as ‘well man’ screening tests. As the disease advances, the patient may develop lymphadenopathy, hepatosplenomegaly, anaemia and infections.

Laboratory findings in CLL include:

  • Clonal B cell lymphocytosis (greater than 5x 109/l for diagnosis, but may be as high as 300 x 109/l)
  • Normocytic, normochromic anaemia present in advanced disease
  • Positive direct antiglobulin test (DAT) in patients with autoimmune-related haemolytic anaemias


Bone marrow aspiration is not necessary in all cases but can assist with making a diagnosis of CLL. Lymph node biopsy is needed if there has been rapid lymph node enlargement, to assess for the possibility of Richter’s syndrome. This is a transformation to a high-grade lymphoma, accompanied by fever, weight loss, and pain.

There is no curative treatment available for CLL, but the disease is treatable with chemotherapy regimens that prolong survival. There is no benefit of early treatment, and the standard treatment of early disease is a ‘watch and wait’ strategy, with examination and blood counts performed every 3-12 months. Chemotherapy is generally reserved for patients with active, symptomatic disease.

The overall prognosis of CLL is as follows:

  • 1/3 will not require any treatment and have a long survival
  • 1/3 will have an initial indolent phase followed by disease progression
  • 1/3 will present with aggressive disease requiring immediate treatment.


Thank you to the joint editorial team of www.plabprep.co.uk for this ‘Exam Tips’ post.


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