Leukaemia is cancer of the white blood cells. Blood cells are produced in the bone marrow from cells called stem cells or blast cells. Bone marrow is found in the long bones of the limbs (although the amount decreases with age), in the skull, vertebrae, pelvis and chest bone (sternum).

Production of blood cells
Blast cells differentiate (mature and become specialised) to form the different types of blood cells, i.e. red blood cells, white blood cells and platelets. Mature cells are then released into the circulation.
Red blood cells carry oxygen around the body to all the organs and tissues. White blood cells fight infection. There are several types of white blood cell including:

• Granulocytes: There are three types of granulocytes - neutrophils, eosinophils and basophils. They all have granules in their cytoplasm (fluid inside the cell). The granules contain enzymes and chemicals that help the cells to fight infection. Eosinophils and basophils also play a role in allergic reactions.

• Monocytes: These remove foreign material, including bacteria, from the blood. They have a role in the body's immune response.

• Lymphocytes: There are two main types of lymphocyte - T cells and B cells. These are the main cells of the immune system. B cells are responsible for antibody production. T cells recognise and attack cells that have been infected by viruses. Once they leave the bone marrow, these cells mature further in the lymph tissue, e.g. lymph nodes and thymus.

Platelets play an important role in clot formation.

Types of leukaemia

There are a number of different types of leukaemia and they are classified according to whether they are acute or chronic and what type of white cell is affected.

Acute leukaemia
An increased production of immature blood cells fills up the bone marrow and interferes with normal bone marrow function. The immature cells are released into the bloodstream and may be deposited in tissues and organs.

The decrease in the number of normal blood cells produced by the bone marrow leads to anaemia due to a deficiency in red blood cells, thrombocytopaenia because of reduced platelet production and neutropaenia due to low neutrophil production.

This increased production of immature blood cells and reduction in normal blood cells is responsible for the signs and symptoms of acute leukaemia.

Acute leukaemia has a more rapid onset and progression than chronic leukaemia. In acute leukaemia, the cancer affects immature blood cells in the bone marrow. There are two main types of acute leukaemia:

• Acute lympoblastic leukaemia (ALL), which arises from blast cells already involved in lymphocyte production, and
• Acute myeloid leukaemia (AML), which arises from precursor cells that are destined to mature into granulocytes, platelets or red blood cells.

Incidence
Acute leukaemia is uncommon and there are about four new cases per 100,000 of the population per year. AML is more common in adults and accounts for over 75 percent of cases. ALL accounts for over 75 percent of acute leukaemia in children and has a peak incidence in early childhood.

Chronic leukaemia
Chronic leukaemia is a more slowly progressive condition. There are two main types of chronic leukaemia:

• Chronic lymphocytic leukaemia (CLL), which arises from mature committed B or, less commonly, T lymphocytes, and
• Chronic myeloid leukaemia (CML), where granulocytes are affected. Although the neoplastic or cancerous cells may appear normal they do not function normally.

CLL is a disease of older people (mainly 60-80 years) and is rare under the age of 40 years. It is twice as common in men as in women. It is the most common chronic leukaemia in adults and accounts for 25 percent of all leukaemias.

CML may occur at any age but is more common in middle age and very rare under five years of age. It has a chronic phase lasting two to three years and then enters a more acute phase.

What causes leukaemia?

The cause of leukaemia is unknown. However, a number of factors may be involved.

Genetic factors
Patients with CML have an abnormal chromosome called the Philadelphia chromosome. This is also found in some cases of chronic B lymphocytic leukaemia.

People who have Downs syndrome, or a condition called Fanconi's anaemia, have an increased risk of acute leukaemia.

Radiation
Exposure to excess levels of ionising radiation increases the risk of developing acute leukaemia. People who are treated with chemotherapy and radiation for other cancers also have an increased risk.

Drugs and chemicals
Chemotherapeutic drugs, drugs that suppress the immune system and chloramphenicol (an antibiotic used to treat bacterial eye infections) increase the risk. So do organic chemicals such as benzene and its derivatives.

What are the signs and symptoms of leukaemia?

The symptoms of leukaemia are often vague and non-specific, especially in chronic leukaemia. In CML, as many as 50% of diagnoses are made incidentally during a check-up.
Depending on the type and stage of leukaemia some or all of the following signs and symptoms may be present:

• Fatigue
• Lack of energy
• Non-specific aches and pains
• Weight loss
• Bone pain, particularly in children
• Easy bruising
• Skin rash
• Blood in the urine or stools
• Recurrent infections
• Fever
• Night sweats (more common in chronic leukaemia)
• Headache
• Enlarged lymph glands in the neck, axillae (armpits) and groin
• Hepatomegaly (an enlarged liver)
• Splenomegaly (an enlarged spleen)
• Thickening of the gums.

How is leukaemia diagnosed?

The following methods may be used to diagnose leukaemia:

• The signs and symptoms may suggest a diagnosis of leukaemia. On examination there may be enlarged lymph glands, hepatomegaly and/or splenomegaly.

• A urine sample is checked for blood.

• Blood tests such as a full blood count will check the number of each type of white blood cell in the sample. It will indicate the presence of anaemia or a reduction in the number of platelets.

• A blood film is done to check the appearance of the blood cells. This involves taking a very small amount of blood from the sample and smearing it on a slide, which is then viewed under a microscope. Immature or abnormal blood cells can be seen on the slide.

• Bone marrow biopsy involves the removal of some bone and marrow from the sternum or the hipbone. This is usually done under local anaesthetic, although in small children general anaesthetic may be required. The sample of bone marrow is spread on a slide and examined under a microscope.

• Special tests such as flow cytometry are used to detect markers on blood cells that help identify the type of leukaemia.

• X-rays, ultrasound, computed tomography (CT) scans or magnetic resonance imaging (MRI) may be required to check if leukaemic cells have been deposited around the body.

How is leukaemia treated?

Chemotherapy, radiotherapy and bone marrow transplant (BMT) are used to treat leukaemia. There are different types of chemotherapy (called protocols) each involving a number of anticancer drugs given at the same time.

The choice of treatment and timing of BMT depends on a number of factors including the patient's age and general health, and the type and stage of the leukaemia.

BMT may be allogenic or autologous. Allogenic BMT requires a donor, often a relative, whose tissue type is a match for that of the patient. With autologous BMT some of the patient's own bone marrow is removed, treated with chemotherapeutic drugs to kill all the abnormal cells and frozen to be used later.

With both types of BMT the patient receives high doses of chemotherapy and radiation to destroy their bone marrow and any leukaemic cells in the body. The donor, or autologous bone marrow, is then injected into the patient. BMT requires specialised care and support to prevent infection or rejection of the bone marrow.

What is the prognosis?

Again, outcome depends on age and general health and on the type and stage of the leukaemia. AML has a poorer prognosis than ALL. However, some types of leukaemia have a 90% cure rate