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Leukemia

Leukemia (leukaemia in Commonwealth English) is a group of blood diseases characterized by malignancies (cancer) of the blood-forming tissues.

The word leukemia tends to be used as an umbrella term. In the 19th century, it was seen as one single, homogenous deadly disease, characterized by a white (leuko-) appearance of blood samples. However, with growing understanding of pathologic and cytologic processes, doctors are now able to differentiate numerous diseases which require different treatment.

Overview

Leukemia, first recognised by the German pathologist Rudolf Virchow in 1847, with the first case described by British pathologist John Hughes Bennett in 1845, starts when bone marrow cells multiply abnormally. This is caused by mutations in the DNA in stem cells. Bone marrow stem cells produce billions of red blood cells and white blood cells each day, respectively carrying oxygen and fighting infection throughout the body. Leukemia is characterised by an excessive production of abnormal white blood cells, overcrowding the bone marrow and often spilling out into the peripheral blood. The infiltration of the bone marrow results in decreased production and function of normal blood cells. Leukemia, dependent on the type, can spread to the lymph nodes, spleen, liver, central nervous system and other organs.

Types

Leukemia is a broad term covering a spectrum of diseases. In leukemia, the diseases are classified according to the type of abnormal cell found most in the blood. Leukemia is also clinically split in to its acute and chronic forms. The four main forms are:

The most common forms in adults are AML and CLL, whereas in children ALL is more prevalent.

Acute leukemias are characterised by the rapid growth of immature blood cells. This crowding makes the bone marrow unable to produce healthy blood cells. Acute forms of leukemia are most common in children and young adults (in fact it is a more common cause of death for children in the US than any other type of malignant disease). Immediate treatment is required in acute leukemias due to the rapid progression and accumulation of the malignant cells, which then spill over into the bloodstream and spread to other organs of the body. If left untreated, the patient will die within months or even weeks.

Chronic leukemias are distinguished by the excessive buildup of relatively mature, but still abnormal, blood cells. Typically taking months to years to progress, the cells are produced at a much higher rate than normal cells, resulting in many abnormal white blood cells in the blood. Chronic leukemia mostly occurs in older people, but can theoretically occur in any age group. Whereas acute leukemia must be treated immediately, chronic forms are sometimes monitored for some time before treatment to ensure maximum effectiveness of therapy.

Symptoms

Damage to the bone marrow results in a lack of blood platelets, which are important in the blood clotting process. This means people with leukemia may become bruised or bleed excessively. Similarly, the red blood cell deficiency leads to anemia, which may cause shortness of breath and fatigue. Bone or joint pain may occur because of cancer spreading to these areas. Headaches and vomiting are indicative of the cancer having disseminated to the central nervous system. Enlarged lymph nodes or splenomegaly (an enlarged spleen) may occur in some types. All symptoms may also be attributable to other diseases; for diagnosis, blood tests and a bone marrow biopsy are required.

Causes

All leukemias are due to mutations in the DNA. Chromosomal translocations (crossing over of parts of chromosomes to others) are common, disrupting specific genes that mediate cell division rate. Mutations may occur spontaneously or as a result of exposure to radiation orcarcinogenic substances. Cytogenetics and immunophenotyping are two laboratory investigations used to determine the type and aggressiveness of the leukemia and the necessity of urgent and active treatment, as well as an indication of prognosis.

Viruses have also been linked, with varying levels of speculation, to some forms of leukemia. Some forms of T-cell leukemia have recently been confirmed to be the result of two viruses. (See adult T-cell leukemia/lymphoma).

In the early 1990s concern was raised in the UK about the effect of nuclear power plants on unborn children, when clusters of leukemia cases were discovered nearby to some of these plants. The effect was speculative because clusters were also found where no nuclear plants were present, and not all plants had clusters around them. Using statistical analysis researchers at Southampton University concluded that a link was present, deducing that radiation damage to men working at the plants had caused genetic abnormalities in their children. After this report British Nuclear Fuels initially advised workers who were being exposed to high levels of radiation not to father children, although they have since withdrawn this advice.

Treatment

The mainstay of treatment of leukemia is chemotherapy, sometimes with the addition of radiation therapy. Because of the severity of some courses, bone marrow transplants are sometimes necessary. Healthy bone marrow transplanted in to the body helps rebuild tissue damaged by the treatment.

Prognosis

27,900 adults and 2,300 children are diagnosed each year with leukemia in the US. Over the last thirty years, the chances of survival have doubled from a 22 per cent survival rate in 1970 to 43 per cent rate in the 1990s. There is however a wide range in prognosis amongst the different types of leukaemia: the outlook for an elderly patient with AML remains very poor, whilst 8 out of 10 children with ALL will now be cured.

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