Leukemia

Leukemia (leukaemia in Commonwealth English) is a cancer of the blood or bone marrow characterized by an abnormal proliferation of white blood cells (leukocytes).

Overview

The word leukemia refers to a group of cancers which affect the white blood cells. In the 19th century, it was seen as one single, homogenous deadly disease, characterized by a white (leuko-) appearance of blood samples. Leukemia was first recognized by the German pathologist Rudolf Virchow in 1847 and the first case was described by British pathologist John Hughes Bennett in 1845.

Leukemia arises in the bone marrow. The bone marrow produces three major types of blood cells.

1. Red blood cells contain hemoglobin and are responsible for carrying oxygen to the body.
2. White blood cells are responsible for fighting infection.
3. Platelets assist with blood clotting.

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, causing the affected area to swell.

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).
• Skin symptoms

Four major types

Leukemia is a broad term covering a spectrum of diseases.

Acute vs. chronic

Leukemia is clinically and pathologically split in to its acute and chronic forms.

• 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 can occur 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.

Lymphoid vs. myeloid

Furthermore, the diseases are classified according to the type of abnormal cell found most in the blood.

• When leukemia affects lymphoid cells, it is called lymphocytic leukemia.

• When myeloid cells are affected, the disease is called myeloid or myelogenous leukemia.

Prevalence of the four major types

Combining these two classifications provides a total of four main categories:

• 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 more commonly in adults than in children. This type of leukemia was previously called acute nonlymphocytic leukemia.
• 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.

Causes

The exact cause of leukemia is unknown but is influenced by both genetic and environmental factors. Leukemias, like other cancers, result from somatic mutations in the DNA which activate oncogenes or inactivate tumour suppressor genes, and disrupt the regulation of cell death, differentiation or division. These mutations may occur spontaneously or as a result of exposure to radiation or carcinogenic substances and are likely influenced by genetic factors. Cohort and case control studies have linked exposure to petrochemicals, such as benzene, and hair dyes to the development of leukaemia.

Viruses have also been linked to some forms of leukemia. Certain cases of ALL are associated with viral infections by either the human immunodeficiency virus (HIV, responsible for AIDS) or human T-lymphotropic virus (HTLV-1 and -2, causing adult T-cell leukemia/lymphoma).

Prognosis and treatment

Prognosis and treatment differ according to the type of leukemia. Treatment of leukemia must be tailored to the type of leukemia and individual patient characteristics. For example, while CLL is an incurable disease with standard chemotherapy, patients may require no treatment (ie. "watchful waiting") for years if they are asymptomatic. In contrast, some patients with AML will die within hours or days of presentation unless intensive combination chemotherapy regimen is given and in some cases will require allogeneic stem cell transplant. This type of regimen would not be suited for an elderly patient or one with significant comorbid conditions.

Current research is directed at targeting the molecular mechanisms of the leukemia. One of the recent successes in targeted therapy is imatinib (Gleevec, Glivec). Imatinib inhibits the Abl tyrosine kinase which is constitutively activated by the bcr/abl translocation found in patients with CML and some patients with ALL.

External links

• FAQ on leukemia
• Information and advocacy for leukemia
• Leukaemia Research Fund (UK)
• The Anthony Nolan Trust (UK)
• Unofficial summary of UKCCS, and of UKCCS publications
• Association of Cancer Online Resource (ACOR) Leukemia Links