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Leukemia

From Academic Kids

Template:DiseaseDisorder infobox

Leukemia (leukaemia in Commonwealth English) is a group of blood diseases characterized by malignancies (cancer) of the blood-forming tissues. Leukemia is the most common childhood cancer in the industrialised world; in the UK, around one in 2000 children are affected.

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.

Contents

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 or tissues.

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, bleed excessively, or develop pinprick bleeds (petechiae).

White blood cells, which are involved in fighting pathogens, may be suppressed or dysfunctional, putting the patient at risk of infection.

Finally, 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.

Some other related symptoms:

  • Fever, chills, and other flu-like symptoms;
  • Weakness and fatigue;
  • Loss of appetite and/or weight;
  • Swollen or bleeding gums;
  • Sweating, especially at night;
  • Bone or joint pain.
  • Neurological symptoms (headache, paralysis, seizures) due to involvement of the brain (acute leukemias)
  • Swelling of the testicle(s) and cause swelling.
  • Skin symptoms

Types

Leukemia is a broad term covering a spectrum of diseases. Leukemia is also clinically split in to its acute and chronic forms. Furthermore, the diseases are classified according to the type of abnormal cell found most in the blood (lymphoid cells or myeloid cells). When leukemia affects lymphoid cells, it is called lymphocytic leukemia. When myeloid cells are affected, the disease is called myeloid or myelogenous leukemia.

The four main forms are:

  • Acute lymphocytic leukemia (ALL) is the most common type of leukemia in young children. This disease also affects adults, especially those age 65 and older.
  • Acute myelogenous leukemia (AML) occurs in both adults and children. This type of leukemia is sometimes called acute nonlymphocytic leukemia (ANLL).
  • Chronic lymphocytic leukemia (CLL) most often affects adults over the age of 55. It sometimes occurs in younger adults, but it almost never affects children.
  • Chronic myelogenous leukemia (CML) occurs mainly in adults. A very small number of children also develop this disease.

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.

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 or carcinogenic 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).

Radiation

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.

Immune system

In April 2005 the UK Childhood Cancer Study (UKCCS), a 15-year study tracking 11,000 children, including 1700 with leukemia, found problems relating to the immune system as a primary cause. In particular, around one in 20 children are born with slight genetic abnormalities which predispose them to leukemia, which appears to be triggered by an exaggerated immune response to infections. The study concluded that a significant factor in these exaggerated responses is children having a history of low exposure to infection - because the immune system was insufficiently trained in dealing with infection. The study found that increased levels of social activity outside the home reduced the risk of leukemia, with the cut in risk greatest in children who attended formal daycare during their first three months of life. [1] (http://www.newscientist.com/article.ns?id=dn7301)

Electromagnetic fields

The UK Childhood Cancer Study (UKCCS) (see above) found no association between electromagnetic fields and the risk of childhood leukaemia [2] (http://www.newscientist.com/article.ns?id=dn7301). A large 2005 Oxford University study (http://bmj.bmjjournals.com/cgi/content/full/330/7503/1290?ehom) did find a statistically significant elevation of childhood leukaemia rates (relative risk 1.7) within 200m of high-voltage overhead power lines (132 to 400 kV), though the authors do not regard this as establishing a definite causal association [3] (http://www.hpa.org.uk/hpa/news/articles/press_releases/2005/050603_childhood_cancer_voltage.htm). A pooled analysis of case-control studies found that children living in homes with high magnetic fields (> 0.4 T) had twice the risk of childhood leukaemia. Further research is needed, but a fair current assessment would be that electromagnetic fields produced by the electric power system are "possibly carcinogenic".

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. Successful bone marrow transplants require precise matching of blood characteristics. Only 20% of leukemia patients have a sibling donor who is a good match. Of those who don't have a sibling match, fewer than a third can find a good match elsewhere.

An alternative to bone marrow transplant is cord blood transplant which uses cells from an umbilical cord to replace the cells damages by leukemia therapies. The cord blood process has an advantage over marrow transplantation in that the cord blood cells have not yet been programmed to attack foreign tissue. This process has been successfully used in children. The potential for success with adults is not as certain as a single umbilical cord contains only one-tenth the number of cells that a typical marrow transplant would supply. In addition, cord blood is slower to develop into a full complement of blood cells. However, mismatched cord transplants are less likely to trigger acute graft-versus-host disease than mismatched bone marrow would.

Not every form of leukemia requires treatment. The chronic leukemias (CML and CLL) may be treated with oral medication or even with "watchful waiting".

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 leukemia: the outlook for an elderly patient with AML remains very poor, whilst 8 out of 10 children with ALL will now be cured.

References

Template:Journal reference issue

External links


Health science - Medicine - Hematology
Hematological malignancy and White blood cells
Leukemia (ALL, AML, CLL, CML) - Lymphoma (Hodgkin's disease, NHL) - Multiple myeloma - MDS - Myelofibrosis - Myeloproliferative disease (Essential thrombocytosis, Polycythemia) - Neutropenia
Red blood cells
Anemia - Hemochromatosis - Sickle-cell anemia - Thalassemia - G6PD - other hemoglobinopathies
Coagulation and Platelets
Thrombosis - Deep venous thrombosis - Pulmonary embolism - Hemophilia - ITP - TTP
af:Leukemie

de:Leukmie fr:Leucmie ia:Leucemia he:לוקימיה lt:Leukemija nl:Leukemie ja:白血病 pl:Białaczka fi:Leukemia sv:Leukemi zh:白血病

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