leukemia

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Definition

A slowly progressing cancer that starts in blood-forming cells of the bone marrow. Leukemias are the result of an abnormal development of leukocytes (white blood cells) and their precursors. Leukemia cells look different than normal cells and do not function properly.

Description

There are four main types of leukemia, which can be further divided into subtypes. When classifying the type of leukemia, the first steps are to determine whether the cancer is lymphocytic or myelogenous (cancer can occur in either the lymphoid or myeloid white blood cells) and whether it is acute or chronic (rapidly or slowly progressing).

Chronic leukemia cells live much longer than normal white blood cells, resulting in an accumulation of too many mature granulocytes or lymphocytes. Chronic leukemia progresses slowly but can develop into an acute form. Major types include chronic lymphocytic leukemia (CLL) and chronic myelocytic leukemia (CML).

—Lata Cherath, Ph.D.; Bob Kirsch

A disease characterized by a progressive and abnormal accumulation of white blood cells, or leukocytes. Leukemic cells are malignant because they have three characteristics common to all cancers: (1) they exhibit uncontrolled growth that is frequently associated with an inability to mature normally; (2) they arise from a single precursor cell; and (3) they disregard anatomic boundaries and metastasize to organs or tissues where leukocytes are not normally found. The expanding clone of leukemic cells infiltrates organs and tissues, particularly the bloodstream and bone marrow, where they disrupt the production of normal cells. The resulting symptoms include fatigue, pallor, infections, bruising and bleeding, and discomfort caused by enlarged organs. In humans, the term leukemia encompasses more than 20 distinct malignancies. See also Blood; Hematopoiesis.

Normal leukocytes are grouped into two primary types or lineages, myeloid and lymphoid, and virtually any cell of either lineage can become leukemic. Leukemias are also divided into broad categories that are based on the cell involved (myeloid or lymphoid) and disease aggressiveness (either acute or chronic). Subclassifications are based on morphologic, cytochemical, immunologic, cytogenetic, and molecular criteria.

Although many agents are suspected of inducing leukemia, for the great majority of cases the etiology is unknown. It appears that no single factor is causative but a number of events must take place before leukemia occurs. The evidence for ionizing radiation as a leukemogenic cofactor is virtually irrefutable. Chronic exposure to high levels of benzene and perhaps related compounds is associated with a tenfold higher risk of developing myeloid leukemia. A clear, strong association has been demonstrated between pharmaceuticals (particularly alkylating agents) that are administered as therapy for a primary cancer and the subsequent development of secondary leukemia, virtually always acute myeloblastic leukemia. A strong association has been shown between the rare adult T-cell leukemia and a retrovirus called human T-cell leukemia virus I, or HTLV-I. Persons with the Down syndrome are 30 times more likely to develop acute, usually lymphoid, leukemia than the rest of the population. In the primary immunodeficiency states, malignancies develop 10,000 times faster than in unaffected persons, and each of the immunodeficiencies is associated with a distinct leukemia. The myelodysplastic syndromes are characterized by ineffective production of normal blood cells and result in low blood cell counts due to abnormal precursor cells in the bone marrow. The abnormal cells are clonal and manifest a spectrum of morphologic and cytogenetic abnormalities. Most have a tendency to evolve into acute leukemia, with the myeloid type predominating. See also Down syndrome; Tumor viruses.

The two major types of leukemia usually differ in signs and symptoms. Acute leukemias have a relatively rapid onset, and those with the disease often experience problems immediately. Chronic leukemias have an insidious course and are frequently discovered during an examination for an unrelated problem. For both types, the most consistent symptoms are nonspecific and include weakness, fatigue, mild weight loss, and low-grade fever.

Practical therapeutic goals for the acute and chronic leukemias are distinct. Without prompt, intensive, in-hospital therapy, the acute leukemias usually cause death within a few months. In acute leukemia, the object of therapy is to totally obliterate the leukemic clone and allow normal bone marrow cells to recover. In the chronic leukemias, standard therapeutic principles are completely different. Many patients who initially require no therapy begin mild forms of outpatient treatment as the disease progresses. The intent is not to cure but to control the disease with minimal toxicity.

Many effective antileukemic agents have been synthesized. Combination therapy incorporates drugs that have different modes of action and different toxicities in order to increase cytotoxic potency, account for leukemic cells that may be resistant to a single agent, and lessen cumulative toxicity in any particular organ or tissue. Most antileukemic drugs act by perturbing enzymes or substrates that are related to deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) synthesis and thus largely affect actively dividing cells. Any treatment must be repeated since the number of leukemic cells may exceed one trillion and a single course of antileukemic drugs will destroy only some of them. See also Chemotherapy.

Perhaps the most dramatic and toxic treatment, bone marrow transplantation has had the most positive impact on the leukemia cure rate. Chemotherapy is administered alone or with radiation therapy in doses much higher than those used in standard antileukemic regimens to abolish the leukemic clone at the expense of the normal stem cells in the bone marrow. Patients would die following such treatment unless “rescued” with cryopreserved stem cells. The stem cells must come from a donor whose human leukocyte antigens match those of the patient's cells as closely as possible. Marrow transplantation is the therapy of choice for eligible patients with chronic myelocytic, relapsed acute lymphoid and acute myeloblastic, and other high-risk leukemias.

The search for therapies that are less toxic and more specific for leukemic cells has focused on substances that are derived from natural (biologic) sources or that affect biologic reactions, some of which are thought to be part of the body's natural defense against cancer. Examples include monoclonal antibodies, cell products manufactured by recombinant DNA technology, and the patient's own killer cells expanded and activated in the laboratory before reinfusion. Although such techniques have proved effective in other cancers, only alpha-interferon is commonly used in leukemia. See also Monoclonal antibodies.

Despite the differences between the acute and chronic leukemias, and despite the fact that the great majority of patients can be brought into a remission or quiescent phase of the disease, leukemia is one of the most lethal malignancies. If cure is considered to be the absence of disease 3 to 5 years after cessation of therapy, only a small fraction of all leukemias are curable. An exception is acute lymphoid leukemia in children, where therapeutic advances have resulted in the attainment of a complete remission in almost all and cures in the majority. See also Cancer (medicine); Oncology.

Definition

Leukemia is a cancer that starts in the organs that make blood, namely the bone marrow and the lymph system. Depending on specific characteristics, leukemia can be divided into two broad types: acute and chronic. Acute leukemias are the rapidly progressing leukemias, while the chronic leukemias progress more slowly. The vast majority of childhood leukemias are of the acute form.

Description

The cells that make up blood are produced in the bone marrow and the lymph system. The bone marrow is the spongy tissue found in the large bones of the body. The lymph system includes the spleen (an organ in the upper abdomen), the thymus (a small organ beneath the breastbone), and the tonsils (an organ in the throat). In addition, the lymph vessels (tiny tubes that branch like blood vessels into all parts of the body) and lymph nodes (pea-shaped organs that are found along the network of lymph vessels) are also parts of the lymph system. The lymph is a milky fluid that contains cells. Clusters of lymph nodes are found in the neck, underarm, pelvis, abdomen, and chest.

The cells found in the blood are the red blood cells (RBCs), which carry oxygen and other materials to all tissues of the body; white blood cells (WBCs) that fight infection; and platelets, which play a part in the clotting of the blood. The white blood cells can be further subdivided into three main types: granulocytes, monocytes, and lymphocytes.

The granulocytes, as their name suggests, have particles (granules) inside them. These granules contain special proteins (enzymes) and several other substances that can break down chemicals and destroy microorganisms, such as bacteria. Monocytes are the second type of white blood cell. They are also important in defending the body against pathogens.

The lymphocytes form the third type of white blood cell. There are two main types of lymphocytes: T lymphocytes and B lymphocytes. They have different functions within the immune system. The B cells protect the body by making "antibodies." Antibodies are proteins that can attach to the surfaces of bacteria and viruses. This "attachment" sends signals to many other cell types to come and destroy the antibody-coated organism. The T cells protect the body against viruses. When a virus enters a cell, it produces certain proteins that are projected onto the surface of the infected cell. The T cells recognize these proteins and make certain chemicals that are capable of destroying the virus-infected cells. In addition, the T cells can destroy some types of cancer cells.

The bone marrow makes stem cells, which are the precursors of the different blood cells. These stem cells mature through stages into either RBCs, WBCs, or platelets.

Chronic Leukemias

In chronic leukemias, the cancer starts in the blood cells made in the bone marrow. The cells mature and only a few remain as immature cells. However, even though the cells mature and appear normal, they do not function as normal cells. Depending on the type of white blood cell that is involved, chronic leukemia can be classified as chronic lymphocytic leukemia or chronic myelogenous leukemia.

Chronic leukemias develop very gradually. The abnormal lymphocytes multiply slowly, but in a poorly regulated manner. They live much longer and thus their numbers build up in the body. The two types of chronic leukemias can be easily distinguished under the microscope. Chronic lymphocytic leukemia (CLL) involves the T or B lymphocytes. B cell abnormalities are more common than T cell abnormalities. T cells are affected in only 5% of the patients. The T and B lymphocytes can be differentiated from the other types of white blood cells based on their size and by the absence of granules inside them. In chronic myelogenous leukemia (CML), the cells that are affected are the granulocytes.

Chronic lymphocytic leukemia (CLL) often shows no early symptoms and may remain undetected for a long time. Chronic myelogenous leukemia (CML), on the other hand, may progress to a more acute form.

Acute Leukemias

In acute leukemia, the maturation process of the white blood cells is interrupted. The immature cells (or "blasts") proliferate rapidly and begin to accumulate in various organs and tissues, thereby affecting their normal function. This uncontrolled proliferation of the immature cells in the bone marrow affects the production of the normal red blood cells and platelets as well.

Acute leukemias are of two types: acute lymphocytic leukemia and acute myelogenous leukemia. Different types of white blood cells are involved in the two leukemias. In acute lymphocytic leukemia (ALL), the T or B lymphocytes become cancerous. The B cell leukemias are more common than T cell leukemias. Acute myelogenous leukemia, also known as acute nonlymphocytic leukemia (ANLL), is a cancer of the monocytes and/or granulocytes.

Leukemias account for 2% of all cancers. Because leukemia is the most common form of childhood cancer, it is often regarded as a disease of childhood. However, leukemias affect nine times as many adults as children. Half of the cases occur in people who are 60 years of age or older. The incidence of acute and chronic leukemias is about the same. According to the estimates of the American Cancer Society (ACS), approximately 29,000 new cases of leukemia were diagnosed in 1998. Internationally, leukemia is the fourth most common cancer among people age 15 to 19 years old.

Causes & Symptoms

Leukemia strikes both sexes and all ages and its cause is mostly unknown. However, chronic leukemia has been linked to genetic abnormalities and environmental factors. For example, exposure to ionizing radiation and to certain organic chemicals, such as benzene, is believed to increase the risk for getting leukemia. A 2003 study from the Electric Power Research Institute showed possible links between metallic drainpipes and childhood baths. Chronic leukemia occurs in some people who are infected with two human retroviruses (HTLV-I and HTLV-II). An abnormal chromosome known as the Philadelphia chromosome is seen in 90% of those with CML. The incidence of chronic leukemia is slightly higher among men than women.

Acute lymphoid leukemia (ALL) is more common among Caucasians than among African-Americans, while acute myeloid leukemia (AML) affects both races equally. The incidence of acute leukemia is slightly higher among men than women. People of Jewish ancestry have a higher likelihood of getting leukemia. A higher incidence of leukemia has also been observed among persons with Down syndrome and some other genetic abnormalities.

A history of diseases that damage the bone marrow, such as aplastic anemia, or a history of cancers of the lymphatic system puts people at a high risk for developing acute leukemias. Similarly, the use of anticancer medications, immunosuppressants, and the antibiotic chloramphenicol also are considered risk factors for developing acute leukemias.

The symptoms of leukemia are generally vague and non-specific. A patient may experience all or some of the following symptoms:

• weakness or chronic fatigue
• fever of unknown origin
• weight loss that is not due to dieting or exercise
• frequent bacterial or viral infections
• headaches
• skin rash
• non-specific bone pain
• easy bruising
• bleeding from gums or nose
• blood in urine or stools
• enlarged lymph nodes and/or spleen
• abdominal fullness

Diagnosis

Like all cancers, leukemias are best treated when found early. There are no screening tests available. If the doctor has reason to suspect leukemia, he or she will conduct a thorough physical examination to look for enlarged lymph nodes in the neck, underarm, and pelvic region. Swollen gums, enlarged liver or spleen, bruises, or pinpoint red rashes all over the body are some of the signs of leukemia. Urine and blood tests may be ordered to check for microscopic amounts of blood in the urine and to obtain a complete differential blood count. This count will give the numbers and percentages of the different cells found in the blood. An abnormal blood test might suggest leukemia, however, the diagnosis has to be confirmed by more specific tests.

A doctor may perform a bone marrow biopsy to confirm the diagnosis of leukemia. During the biopsy, a cylindrical piece of bone and marrow is removed, generally from the hip bone. These samples are sent to the laboratory for examination. In addition to diagnosis, the biopsy is also repeated during the treatment phase of the disease to see if the leukemia is responding to therapy.

A spinal tap (lumbar puncture) is another procedure that the doctor may order to diagnose leukemia. In this procedure, a small needle is inserted into the spinal cavity in the lower back to withdraw some cerebrospinal fluid and to look for leukemic cells.

Standard imaging tests, such as x rays, computed tomography scans (CT scans), and magnetic resonance imaging (MRI) may be used to check whether the leukemic cells have invaded other areas of the body, such as the bones, chest, kidneys, abdomen, or brain. A gallium scan or bone scan is a test in which a radioactive chemical is injected into the body. This chemical accumulates in the areas of cancer or infection, allowing them to be viewed with a special camera.

Treatment

Alternative therapies should be used only as complementary to conventional treatment, not to replace it. Before participating in any alternative treatment programs, patients should consult their doctors concerning the appropriateness and the role of such programs in the overall cancer treatment plan. Appropriate alternative treatments can help prolong a patient's life or at least improve quality of life, prevent recurrence of tumors or prolong the remission period, and reduce adverse reactions to chemotherapy and radiation.

The effectiveness of most anti-cancer drugs used to treat leukemia can be reduced when patients take mega doses of antioxidants. These antioxidants, in patients not undergoing chemotherapy, can be very helpful in protecting the body against cancer. However, taken during chemotherapy, these antioxidants protect the cancer cells from being killed by treatment. Because high-dose supplementation of antioxidants can interfere with conventional chemotherapy treatment, patients should only take them at dosages much above the recommended daily allowance (RDA).

Dietary Guidelines

The following dietary changes may be helpful:

• Avoiding fatty and spicy foods, which may be harder to digest.
• Eating new and exciting foods. Tasty foods stimulate appetite so that patients can eat more and have the energy to fight cancer.
• Increasing consumption of fresh fruits and vegetables. They are nature's best sources of antioxidants, as well as vitamins and minerals.
• Eating multiple (five or six) meals per day. Small meals are easier to digest.
• Establishing regular eating times and not eating around bedtime.
• Avoiding foods that contain preservatives or artificial coloring.
• Monitoring weight and eating adequate calories and protein.

Nutritional Supplements

A naturopath or nutritional physician may recommend some of the following nutritional supplements to boost a patient's immune function and help fight cancer:

• Vitamins and minerals. Vitamins that are of particular benefit to cancer patients include beta-carotene, B-complex vitamins, (especially vitamin B6, vitamins A, C, D, E and K. The most important minerals are calcium, chromium, copper, iodine, molybdenum, germanium, selenium, tellurium, and zinc. Many of these vitamins and minerals are strong antioxidants. However, patients should not take mega doses of these supplements without first consulting their doctor. Significant adverse or toxic effects may occur at high dosage, which is especially true for minerals. It is prudent to avoid use of antioxidants when undergoing chemotherapy or radiation therapy since these treatments kill the cancer by producing oxidants. Antioxidants can undermine the effectiveness of treatment.
• Other nutritional supplements that may help fight cancer and support the body include essential fatty acids (fish or flaxseed oil), flavonoids, pancreatic enzymes (to help digest foods), hormones such as DHEA, melatonin or phytoestrogens, rice bran, and mushroom extracts. It is best to check with a nutritional physician or other licensed provider when adding these supplements.

Traditional Chinese Medicine

Conventional treatment for leukemia is associated with significant side effects. These adverse effects can be reduced with Chinese herbal preparations. Patients should consult an experienced herbalist who will prescribe remedies to treat specific symptoms that are caused by conventional cancer treatments.

Juice Therapy

Juice therapy may be helpful in patients with cancer. Patients should mix one part of pure juice with one part of water before drinking. Daily consumption of the following juice may be helpful by reducing toxic burden to the liver:

• carrot and beet juice with a touch of radish or dandelion root
• grapes, pear, and lemon
• carrot, celery, and parsley
• carrot, beet, and cucumber juices

Homeopathy

There is conflicting evidence regarding the effectiveness of homeopathy in cancer treatment. Because cancer chemotherapy may suppress the body's response to homeopathic treatment, homeopathy may not be effective during chemotherapy. Therefore, patients should wait until after chemotherapy to try this relatively safe alternative treatment.

Acupuncture

Acupuncture is the use of needles on the body to stimulate or direct the meridians (channels) of energy flow in the body. Acupuncture has not been shown to have any anticancer effects. However, it is an effective treatment for nausea, a common side effect of chemotherapy and radiation.

Other Treatments

Other therapies that may help the leukemia patient include meditation, qigong, yoga, and t'ai chi, all of which can aid in stress reduction. Guided imagery can increase immune function and decrease pain and nausea.

Allopathic Treatment

There are two phases of treatment for leukemia. The first phase is called induction therapy. The main aim of the treatment is to reduce the number of leukemic cells as far as possible and induce a remission in the patient. Once the patient shows no obvious signs of leukemia (no leukemic cells are detected in blood tests and bone marrow biopsies), the patient is said to be in remission. The second phase of treatment is then initiated. This is called continuation or maintenance therapy; the aim in this case is to kill any remaining cells and to maintain remission for as long as possible.

Chemotherapy is the use of drugs to kill cancer cells. It is usually the treatment of choice and is used to relieve symptoms and achieve long-term remission of the disease. Generally, combination chemotherapy, in which multiple drugs are used, is more efficient than using a single drug for treatment.

In 2002, scientists announced the discovery of a gene that triggers the death of leukemia cells. Identification of this gene can lead to better targeting of chemotherapy drugs (that involve a vitamin A derivative) for acute promyelocytic leukemia (APL). Another advancement in leukemia treatment occurred in the same year. A new drug was found to cancel the effects of mutations of a gene known as the main culprit in AML, an aggressive, treatment-resistant form of leukemia. Further study was needed on both new discoveries, but they were thought important to improving treatment of two forms of leukemia. Later in 2002, Gleevec, a new antileukemia drug that even proved successful at treating chronic myeloid leukemia, was heralded in clinical trials.

Because leukemia cells can spread to all the organs via the blood stream and lymph vessels, surgery is not considered an option for treating leukemias.

Radiation therapy, which involves the use of x rays or other high-energy rays to kill cancer cells and shrink tumors, may be used in some cases. For acute leukemias, the source of radiation is usually outside the body (external radiation therapy). If the leukemic cells have spread to the brain, radiation therapy can be given to the brain.

Bone marrow transplantation (BMT) is a process in which the patient's diseased bone marrow is replaced with healthy marrow. There are two methods of bone marrow transplant. In an allogeneic bone marrow transplant, healthy marrow is taken from a donor whose tissue is either the same as or very closely resembles the patient's tissue. First, the patient's bone marrow is destroyed with very high doses of chemotherapy and radiation therapy. Healthy marrow from the donor is then given to the patient through a needle in a vein to replace the destroyed marrow.

In the second type of bone marrow transplant, called an autologous bone marrow transplant, some of the patient's own marrow is taken out and treated with a combination of anticancer drugs to kill all abnormal cells. This marrow is then frozen and saved. The marrow remaining in the patient's body is destroyed with high-dose chemotherapy and radiation therapy. The marrow that was frozen is then thawed and given back to the patient through a needle in a vein. This mode of bone marrow transplant is currently being investigated in clinical trials.

Biological therapy or immunotherapy is a mode of treatment in which the body's own immune system is harnessed to fight the cancer. Substances that are routinely made by the immune system (such as growth factors, hormones, and disease-fighting proteins) are either synthetically made in a laboratory or their effectiveness is boosted and they are then put back into the patient's body. This treatment mode is also being investigated in clinical trials all over the country at major cancer centers.

Expected Results

Like all cancers, the prognosis for leukemia depends on the patient's age and general health. According to statistics, more than 60% of leukemia patients survive for at least one year after diagnosis.

Acute myelocytic leukemia (AML) has a poorer prognosis rate than acute lymphocytic leukemias (ALL) and the chronic leukemias. In the last 15 to 20 years, the five-year survival rate for patients with ALL has increased from 38% to 57%.

Interestingly enough, since most childhood leukemias are of the ALL type, chemotherapy has been highly successful in their treatment. This is because chemotherapeutic drugs are most effective against actively growing cells. Due to the new combinations of anti-cancer drugs being used, the survival rates among children with ALL have improved dramatically. Eighty percent of the children diagnosed with ALL now survive five years or more, as compared to 50% in the late 1970s.

According to statistics, in chronic lymphoid leukemia, the overall survival for all stages of the disease is nine years. Most of the deaths in people with CLL are due to infections or other illnesses that occur as a result of the leukemia.

In CML, if bone marrow transplantation is performed within one to three years of diagnosis, 50-60% of the patients survive three years or more. If the disease progresses to the acute phase, the prognosis is poor. Less than 20% of these patients go into remission.

Prevention

Most cancers can be prevented by changes in lifestyle or diet, which will reduce risk factors. However, in leukemias, there are no such known risk factors. Therefore, at the present time, there are no real prevention recommendations for leukemia. People who are at an increased risk for developing leukemia because of proven exposure to ionizing radiation or exposure to the toxic liquid benzene, and people with Down syndrome, should undergo periodic medical checkups. Some experts recommend limiting toxic exposures, eating a whole foods diet, refraining from smoking, exercise, and fluids, and even intermittent fasting as possible prevention measures. In 2003, new research found that adult women who took aspirin two or more times a week had a 50% lower risk of developing adult leukemia. Scientists continue to work on a possible vaccine for leukemia. They made some progress in 2002, discovering a gene transfer model that might trigger immunity against leukemia cells.

Resources

Books

Berkow, Robert, et al., eds. Merck Manual of Diagnosis and Therapy, 16th ed. Merck Research Laboratories, 1992.

Dollinger, Malin. Everyone's Guide to Cancer Therapy. Somerville House Books Limited, 1994.

Labriola, Dan. Complementary Cancer Therapies: Combining Traditional and Alternative Approaches for the Best Possible Outcome. Roseville, CA: Prima Health, 2000.

Morra, Marion E. Choices. Avon Books, 1994.

Murphy, Gerald P. Informed Decisions: The Complete Book of Cancer Diagnosis, Treatment and Recovery. American Cancer Society, 1997.

Periodicals

"Cancer Killing Gene Found by Dartmouth Researchers." Cancer Weekly (April 9, 2002):17.

"Contact Voltage and Magnetic Fields as Possible Factors in Leukemia — Pilot Study." Journal of Environmental Health (December 2002):47–51.

"Cytokine and CD154 Gene Transfer Generate Immunity Against Leukemia." Immunotherapy Weekly (October 23, 2002):16.

"Drug Blocks Gene Mutation Effect in Lethal Leukemia." Genomics & Genetics Weekly (June 21, 2002):13.

"Leukemia Incidence Lowest in Patients 15-30 Years of Age (Incidence Drops at Age 20)." Internal Medicine News (May 1, 2002):37.

"New Drug Significantly Improves Survival Even for Patients with Late-Stage Disease." Cancer Weekly (December 31, 2002):6.

"Study: Regular Use of Aspirin May Lower Risk of Adult Leukemia." Women's Health Weekly (July 10, 2003):36.

Organizations

American Cancer Society. 1599 Clifton Road, N.E., Atlanta, Georgia 30329. (800) 227-2345. http://www.cancer.org.

Cancer Research Institute. 681 Fifth Avenue, New York, N.Y. 10022. (800) 992-2623. http://www.cancerresearch.org.

The Leukemia and Lymphoma Society. 600 Third Avenue, New York, NY 10016. (800) 955-4572. http://www.leukemia.org.

National Cancer Institute. 9000 Rockville Pike, Building 31, Room 10A16, Bethesda, Maryland, 20892. (800) 422-6237. http://wwwicic.nci.nih.gov.

Oncolink. University of Pennsylvania Cancer Center. http://cancer.med.upenn.edu.

Other

Rosenberg, Z'ev. "Treating the Undesirable Effect of Radiation and Chemotherapy with Chinese Medicine." Oriental Chinese Journal.http://www.healthypeople.com.

[Article by: Mai Tran; Teresa G. Odle]

A kind of cancer in which the number of white blood cells in the blood greatly increases. Leukemia usually spreads to the spleen, liver, lymph nodes, and other areas of the body, causing destruction of tissues and often resulting in death.

A progressive, malignant disease of the blood-forming organs, marked by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Signs include fever and enlargement of the lymph nodes, spleen and liver. The persistent lymphocytosis that occurs in some cattle is a response to infection with the bovine viral leukosis virus. Similarly, leukemia may occur in the lymphoproliferative and myeloproliferative diseases caused by feline leukemia virus in cats.

• aleukemic l. — leukemia in which the leukocyte count is normal or below normal.
• avian l. — see avian leukosis.
• basophilic l., basophilocytic l. — leukemia in which basophilic granulocytes predominate.
• B-cell l. — leukemia arising from B lymphocytes.
• bovine l. — see bovine viral leukosis.
• l. cutis — skin lesions associated with dissemination of systemic leukemia; they may be neoplastic or nonspecific.
• embryonal l. — stem cell leukemia.
• eosinophilic l. — occurs rarely in cats. There are large numbers of eosinophils with infiltration of spleen, liver, lymph nodes and bone marrow.
• feline l. complex — the array of diseases associated with infection of cats by the feline leukemia virus; includes lymphoreticular neoplasms, myelodysplastic disorders and abnormalities of the immune system.
• feline l. virus (FeLV) — see feline leukemia virus.
• granulocytic l. — myelocytic leukemia.
• leukopenic l. — aleukemic leukemia.
• lymphatic l., lymphoblastic l., lymphocytic l., lymphogenous l., lymphoid l. — leukemia associated with hyperplasia and overactivity of the lymphoid tissue, in which the leukocytes are lymphocytes or lymphoblasts.
• lymphosarcoma cell l. — a form marked by large numbers of lymphosarcoma cells in the peripheral blood; depending on the degree of bone marrow involvement, it may be a variant of lymphosarcoma.
• mast cell l. — a form marked by overwhelming numbers of tissue mast cells in the peripheral blood.
• megakaryoblastic l. — a rare disease of young dogs, characterized by intestinal hemorrhage, anemia and a fatal outcome within a few weeks. There is a pancytopenia and marked thrombocytopenia.
• megakaryocytic l. — a form with numerous megakaryocytes in the spleen, bone marrow, and other tissues, but decreased numbers or abnormal thrombocytes in the peripheral blood, and anemia. Reported in dogs and cats. Called also megakaryocytic myelosis.
• monocytic l. — leukemia in which the predominating leukocytes are monocytes.
• myeloblastic l. — characterized by a predominance of immature myeloid series of cells in the blood; largely a disease of young male dogs and cats.
• myelocytic l., myelogenous l., myeloid l. — a form arising from myeloid tissue in which the granular polymorphonuclear leukocytes and their precursors predominate.
• myelomonocytic l. — concurrent neoplasia of the neutrophilic and monocytic cell lines with a monocytic leukemia, a high total leukocyte count, anemia and thrombocytopenia.
• plasma cell l., plasmacyte l. — a form in which the predominating cell in the peripheral blood is the plasma cell.
• premyelocytic l. — a form in which the predominant cells are premyeloblasts, rather than myeloblasts, often associated with abnormal bleeding secondary to thrombocytopenia, hypofibrinogenemia and decreased levels of clotting factor V.
• promyelocytic l. — characterized by a predominance of promyelocytes in peripheral blood and in the bone marrow. A disease of dogs and cats with bleeding tendencies, anemia and a susceptibility to septicemia with a fatal outcome within a few weeks.
• stem cell l. — leukemia in which the predominating cell is so immature and primitive that its classification is difficult.
• subleukemic l. — aleukemic leukemia.
• undifferentiated l. — an acute myeloproliferative disorder in which the cells involved cannot be identified.

Leukemia
Classification and external resources
A Wright's stained bone marrow aspirate smear of patient with precursor B-cell acute lymphoblastic leukemia.
ICD-10	C91.-C95.
ICD-9	208.9
ICD-O:	9800-9940
DiseasesDB	7431
MeSH	D007938

Leukemia (British/Canadian English: leukaemia) (Greek leukos λευκός, "white"; aima αίμα, "blood") is a cancer of the blood or bone marrow and is characterized by an abnormal proliferation (production by multiplication) of blood cells, usually white blood cells (leukocytes). Leukemia is a broad term covering a spectrum of diseases. In turn, it is part of the even broader group of diseases called hematological neoplasms.

Contents 1 Classification 2 Signs and symptoms 3 Causes 4 Treatment 4.1 Acute lymphoblastic leukemia (ALL) 4.2 Chronic lymphocytic leukemia (CLL) 4.3 Acute myelogenous leukemia (AML) 4.4 Chronic myelogenous leukemia (CML) 4.5 Hairy cell leukemia (HCL) 4.6 T-cell prolymphocytic leukemia (T-PLL) 5 Epidemiology 6 Research 7 See also 8 References 9 External links

Classification

Leukemia is clinically and pathologically subdivided into a variety of large groups. The first division is between its acute and chronic forms:

• Acute leukemia is characterized by the rapid increase of immature blood cells. This crowding makes the bone marrow unable to produce healthy blood cells. Immediate treatment is required in acute leukemia 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. Acute forms of leukemia are the most common forms of leukemia in children.
• Chronic leukemia is distinguished by the excessive build up of relatively mature, but still abnormal, white blood cells. Typically taking months or 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. Whereas acute leukemia must be treated immediately, chronic forms are sometimes monitored for some time before treatment to ensure maximum effectiveness of therapy. Chronic leukemia mostly occurs in older people, but can theoretically occur in any age group.

Additionally, the diseases are subdivided according to which kind of blood cell is affected. This split divides leukemias into lymphoblastic or lymphocytic leukemias and myeloid or myelogenous leukemias:

• In lymphoblastic or lymphocytic leukemias, the cancerous change takes place in a type of marrow cell that normally goes on to form lymphocytes, which are infection-fighting immune system cells. Most lymphocytic leukemias involve a specific subtype of lymphocyte, the B cell.
• In myeloid or myelogenous leukemias, the cancerous change takes place in a type of marrow cell that normally goes on to form red blood cells, some other types of white cells, and platelets.

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

Four major kinds of leukemia

Cell type	Acute	Chronic
Lymphocytic leukemia (or "lymphoblastic")	Acute lymphoblastic leukemia (ALL)	Chronic lymphocytic leukemia (CLL)
Myelogenous leukemia (also "myeloid" or "nonlymphocytic")	Acute myelogenous leukemia (AML)	Chronic myelogenous leukemia (CML)

Within these main categories, there are typically several subcategories. Finally, hairy cell leukemia and T-cell prolymphocytic leukemia are usually considered to be outside of this classification scheme.

• Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in young children. This disease also affects adults, especially those age 65 and older. Standard treatments involve chemotherapy and radiation. The survival rates vary by age: 85% in children and 50% in adults.^[1] Subtypes include precursor B acute lymphoblastic leukemia, precursor T acute lymphoblastic leukemia, Burkitt's leukemia, and acute biphenotypic 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. Two-thirds of affected people are men. The five-year survival rate is 75%.^[2] It is incurable, but there are many effective treatments. One subtype is B-cell prolymphocytic leukemia, a more aggressive disease.
• Acute myelogenous leukemia (AML) occurs more commonly in adults than in children, and more commonly in men than women. AML is treated with chemotherapy. The five-year survival rate is 40%.^[3] Subtypes of AML include acute promyelocytic leukemia, acute myeloblastic leukemia, and acute megakaryoblastic leukemia.
• Chronic myelogenous leukemia (CML) occurs mainly in adults. A very small number of children also develop this disease. Treatment is with imatinib (Gleevec) or other drugs. The five-year survival rate is 90%.^[4][5] One subtype is chronic monocytic leukemia.
• Hairy cell leukemia (HCL) is sometimes considered a subset of CLL, but does not fit neatly into this pattern. About 80% of affected people are adult men. There are no reported cases in young children. HCL is incurable, but easily treatable. Survival is 96% to 100% at ten years.^[6]
• T-cell prolymphocytic leukemia (T-PLL) is a very rare and aggressive leukemia affecting adults; somewhat more men than women are diagnosed with this disease.^[7] Despite its overall rarity, it is also the most common type of mature T cell leukemia;^[8] nearly all other leukemias involve B cells. It is difficult to treat, and the median survival is measured in months.
• Large granular lymphocytic leukemia may involve either T cell or NK cells; like hairy cell leukemia, which involves solely B cells, it is a rare and indolent (not aggressive) leukemia.

Signs and symptoms

Common symptoms of chronic or acute leukemia.^[9]

Damage to the bone marrow, by way of displacing the normal bone marrow cells with higher numbers of immature white blood cells, results in a lack of blood platelets, which are important in the blood clotting process. This means people with leukemia may easily become bruised, bleed excessively, or develop pinprick bleeds (petechiae).

White blood cells, which are involved in fighting pathogens, may be suppressed or dysfunctional. This could cause the patient's immune system to be unable to fight off a simple infection or to start attacking other body cells. Because leukemia prevents the immune system from working normally, some patients experience frequent infection, ranging from infected tonsils, sores in the mouth, or diarrhea to life-threatening pneumonia or opportunistic infections.

Finally, the red blood cell deficiency leads to anemia, which may cause dyspnea and pallor.

Some patients experience other symptoms. These symptoms might include feeling sick, such as having fevers, chills, night sweats and other flu-like symptoms, or feeling fatigued. Some patients experience nausea or a feeling of fullness due to an enlarged liver and spleen; this can result in unintentional weight loss. If the leukemic cells invade the central nervous system, then neurological symptoms (notably headaches) can occur.

All symptoms associated with leukemia can be attributed to other diseases. Consequently, leukemia is always diagnosed through medical tests.

The word leukemia, which means 'white blood', is derived from the disease's namesake high white blood cell counts that most leukemia patients have before treatment. The high number of white blood cells are apparent when a blood sample is viewed under a microscope. Frequently, these extra white blood cells are immature or dysfunctional. The excessive number of cells can also interfere with the level of other cells, causing a harmful imbalance in the blood count.

Some leukemia patients do not have high white blood cell counts visible during a regular blood count. This less-common condition is called aleukemia. The bone marrow still contains cancerous white blood cells which disrupt the normal production of blood cells. However, the leukemic cells are staying in the marrow instead of entering the bloodstream, where they would be visible in a blood test. For an aleukemic patient, the white blood cell counts in the bloodstream can be normal or low. Aleukemia can occur in any of the four major types of leukemia, and is particularly common in hairy cell leukemia.

Causes

No single known cause for all of the different types of leukemia exists. The known causes, which are not generally factors within the control of the average person, account for relatively few cases.^[10] The different leukemias likely have different causes.

Leukemia, like other cancers, results from somatic mutations in the DNA. Certain mutations produce leukemia by activating oncogenes or deactivating tumor suppressor genes, and thereby disrupting 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 to be influenced by genetic factors.

Among adults, the known causes are natural and artificial ionizing radiation, a few viruses such as Human T-lymphotropic virus, and some chemicals, notably benzene and alkylating chemotherapy agents for previous malignancies.^[11][12][13] Use of tobacco is associated with a small increase in the risk of developing acute myeloid leukemia in adults.^[11] Cohort and case-control studies have linked exposure to some petrochemicals and hair dyes to the development of some forms of leukemia. A few cases of maternal-fetal transmission have been reported.^[11] Diet has very limited or no effect, although eating more vegetables may confer a small protective benefit.^[10]

Viruses have also been linked to some forms of leukemia. For example, certain cases of ALL are associated with viral infections by either the human immunodeficiency virus or human T-lymphotropic virus (HTLV-1 and -2, causing adult T-cell leukemia/lymphoma). However, one report suggests exposure to certain germs may offer children limited protection against leukemia.

Some people have a genetic predisposition towards developing leukemia. This predisposition is demonstrated by family histories and twin studies.^[11] The affected people may have a single gene or multiple genes in common. In some cases, families tend to develop the same kind of leukemia as other members; in other families, affected people may develop different forms of leukemia or related blood cancers.^[11]

In addition to these genetic issues, people with chromosomal abnormalities or certain other genetic conditions have a greater risk of leukemia.^[12] For example, people with Down syndrome have a significantly increased risk of developing forms of acute leukemia, and Fanconi anemia is a risk factor for developing acute myeloid leukemia.^[11]

Whether non-ionizing radiation causes leukemia has been studied for several decades. The International Agency for Research on Cancer expert working group undertook a detailed review of all data on static and extremely low frequency electromagnetic energy, which occurs naturally and in association with the generation, transmission, and use of electrical power.^[14] They concluded that there is limited evidence that high levels of ELF magnetic (but not electric) fields might cause childhood leukemia. Exposure to significant ELF magnetic fields might result in twofold excess risk for leukemia for children exposed to these high levels of magnetic fields.^[14] However, the report also says that methodological weaknesses and biases in these studies have likely caused the risk to be overstated.^[14] No evidence for a relationship to leukemia or an other form of malignancy in adults has been demonstrated.^[14] Since exposure to such levels of ELFs is relatively uncommon, the World Health Organization concludes that ELF exposure, if later proven to be causative, would account for just 100 to 2400 cases worldwide each year, representing 0.2 to 4.95% of the total incidence for that year.^[15]

Until the cause or causes of leukemia are found, there is no way to prevent the disease. Even when the causes become known, they may not be readily controllable, such as naturally occurring background radiation, and therefore not especially helpful for prevention purposes.

Treatment

Most forms of leukemia are treated with pharmaceutical medications. Some are also treated with radiation therapy. In some cases, a bone marrow transplant is useful.

Acute lymphoblastic leukemia (ALL)

Further information: Acute lymphoblastic leukemia#Treatment

Management of ALL focuses on control of bone marrow and systemic (whole-body) disease. Additionally, treatment must prevent leukemic cells from spreading to other sites, particularly the central nervous system (CNS) e.g. monthly lumbar punctures. In general, ALL treatment is divided into several phases:

• Induction chemotherapy to bring about bone marrow remission. For adults, standard induction plans include prednisone, vincristine, and an anthracycline drug; other drug plans may include L-asparaginase or cyclophosphamide. For children with low-risk ALL, standard therapy usually consists of three drugs (prednisone, L-asparaginase, and vincristine) for the first month of treatment.
• Consolidation therapy or intensification therapy to eliminate any remaining leukemia cells. There are many different approaches to consolidation, but it is typically a high-dose, multi-drug treatment that is undertaken for a few months. Patients with low- to average-risk ALL receive therapy with antimetabolite drugs such as methotrexate and 6-mercaptopurine (6-MP). High-risk patients receive higher drug doses of these drugs, plus additional drugs.
• CNS prophylaxis (preventive therapy) to stop the cancer from spreading to the brain and nervous system in high-risk patients. Standard prophylaxis may include radiation of the head and/or drugs delivered directly into the spine.
• Maintenance treatments with chemotherapeutic drugs to prevent disease recurrence once remission has been achieved. Maintenance therapy usually involves lower drug doses, and may continue for up to three years.
• Alternatively, allogeneic bone marrow transplantation may be appropriate for high-risk or relapsed patients.

Chronic lymphocytic leukemia (CLL)

Further information: Chronic lymphocytic leukemia#Treatment

Decision to treat
Hematologists base CLL treatment upon both the stage and symptoms of the individual patient. A large group of CLL patients have low-grade disease, which does not benefit from treatment. Individuals with CLL-related complications or more advanced disease often benefit from treatment. In general, the indications for treatment are:

• falling hemoglobin or platelet count
• progression to a later stage of disease
• painful, disease-related overgrowth of lymph nodes or spleen
• an increase in the rate of lymphocyte production

Typical treatment approach
CLL is probably incurable by present treatments. The primary chemotherapeutic plan is combination chemotherapy with chlorambucil or cyclophosphamide, plus a corticosteroid such as prednisone or prednisolone. The use of a corticosteroid has the additional benefit of suppressing some related autoimmune diseases, such as immunohemolytic anemia or immune-mediated thrombocytopenia. In resistant cases, single-agent treatments with nucleoside drugs such as fludarabine, pentostatin, or cladribine may be successful. Younger patients may consider allogeneic or autologous bone marrow transplantation.

Acute myelogenous leukemia (AML)

Further information: Acute myeloid leukemia#Treatment

Many different anti-cancer drugs are effective for the treatment of AML. Treatments vary somewhat according to the age of the patient and according to the specific subtype of AML. Overall, the strategy is to control bone marrow and systemic (whole-body) disease, while offering specific treatment for the central nervous system (CNS), if involved.

In general, most oncologists rely on combinations of drugs for the initial, induction phase of chemotherapy. Such combination chemotherapy usually offers the benefits of early remission and a lower risk of disease resistance. Consolidation and maintenance treatments are intended to prevent disease recurrence. Consolidation treatment often entails a repetition of induction chemotherapy or the intensification chemotherapy with additional drugs. By contrast, maintenance treatment involves drug doses that are lower than those administered during the induction phase.

Chronic myelogenous leukemia (CML)

Further information: Chronic myelogenous leukemia#Treatment

There are many possible treatments for CML, but the standard of care for newly diagnosed patients is imatinib (Gleevec) therapy.^[16] Compared to most anti-cancer drugs, it has relatively few side effects and can be taken orally at home. With this drug, more than 90% of patients will be able to keep the disease in check for at least five years,^[16] so that CML becomes a chronic, manageable condition.

In a more advanced, uncontrolled state, when the patient cannot tolerate imatinib, or if the patient wishes to attempt a permanent cure, then an allogeneic bone marrow transplantation may be performed. This procedure involves high-dose chemotherapy and radiation followed by infusion of bone marrow from a compatible donor. Approximately 30% of patients die from this procedure.^[16]

Hairy cell leukemia (HCL)

Further information: Hairy cell leukemia#Treatment

Decision to treat
Patients with hairy cell leukemia who are symptom-free typically do not receive immediate treatment. Treatment is generally considered necessary when the patient shows signs and symptoms such as low blood cell counts (e.g., infection-fighting neutrophil count below 1.0 K/µL), frequent infections, unexplained bruises, anemia, or fatigue that is significant enough to disrupt the patient's everyday life.

Typical treatment approach
Patients who need treatment usually receive either one week of cladribine, given daily by intravenous infusion or a simple injection under the skin, or six months of pentostatin, given every four weeks by intravenous infusion. In most cases, one round of treatment will produce a prolonged remission.

Other treatments include rituximab infusion or self-injection with Interferon-alpha. In limited cases, the patient may benefit from splenectomy (removal of the spleen). These treatments are not typically given as the first treatment because their success rates are lower than cladribine or pentostatin.

T-cell prolymphocytic leukemia (T-PLL)

Further information: T-cell prolymphocytic leukemia#Treatment

Most patients with T-cell prolymphocytic leukemia, a rare and aggressive leukemia with a median survival of less than one year, require immediate treatment.^[17]

T-cell prolymphocytic leukemia is difficult to treat, and it does not respond to most available chemotherapeutic drugs.^[17] Many different treatments have been attempted, with limited success in certain patients: purine analogues (pentostatin, fludarabine, cladribine), chlorambucil, and various forms of combination chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone [CHOP], cyclophosphamide, vincristine, prednisone [COP], vincristine, doxorubicin, prednisone, etoposide, cyclophosphamide, bleomycin [VAPEC-B]). Alemtuzumab (Campath), a monoclonal antibody that attacks white blood cells, has been used in treatment with greater success than previous options.^[17]

Some patients who successfully respond to treatment also undergo stem cell transplantation to consolidate the response.^[17]

Epidemiology

Age-standardized death from leukemia per 100,000 inhabitants in 2004.^[18]

     no data      less than 1      1-2      2-3      3-4      4-5      5-6      6-7      7-8      8-9      9-10      10-11      more than 11

In 2000, approximately 256,000 children and adults around the world developed a form of leukemia, and 209,000 died from it.^[19] This represents about 3% of the almost seven million deaths due to cancer that year, and about 0.35% of all deaths from any cause.^[19] Of the sixteen separate sites the body compared, leukemia was the 12th most common class of neoplastic disease, and the 11th most common cause of cancer-related death.^[19]

About 245,000 people in the United States are affected with some form of leukemia, including those that have achieved remission or cure. Approximately 44,270 new cases of leukemia were diagnosed in the year of 2008 in the US.^[20] This represents 2.9% of all cancers (excluding simple basal cell and squamous cell skin cancers) in the United States, and 30.4% of all blood cancers.^[21]

Among children with some form of cancer, about a third have a type of leukemia, most commonly acute lymphoblastic leukemia.^[20] Only about 3% cancer diagnoses among adults are for leukemias, but because cancer is much more common among adults, more than 90% of all leukemias are diagnosed in adults.^[20]

Research

Significant research into the causes, diagnosis, treatment, and prognosis of leukemia is being done. Hundreds of clinical trials are being planned or conducted at any given time. Studies may focus on effective means of treatment, better ways of treating the disease, improving the quality of life for patients, or appropriate care in remission or after cures.

See also

• Antileukemic drugs, medications used to kill leukemia cells
• Hematologic diseases, the large class of blood-related disorders, including leukemia
• Alfred François Donné, who described leukemia in 1844
• List of circulatory system conditions

References

1. ^ Jameson, J. N. St C.; Dennis L. Kasper; Harrison, Tinsley Randolph; Braunwald, Eugene; Fauci, Anthony S.; Hauser, Stephen L; Longo, Dan L. (2005). Harrison's principles of internal medicine. New York: McGraw-Hill Medical Publishing Division. ISBN 0-07-140235-7. 
2. ^ Finding Cancer Statistics » Cancer Stat Fact Sheets »Chronic Lymphocytic Leukemia National Cancer Institute.
3. ^ Colvin GA, Elfenbein GJ (2003). "The latest treatment advances for acute myelogenous leukemia". Med Health R I 86 (8): 243–6. PMID 14582219. 
4. ^ Patients with Chronic Myelogenous Leukemia Continue to Do Well on Imatinib at 5-Year Follow-Up Medscape Medical News 2006.
5. ^ Updated Results of Tyrosine Kinase Inhibitors in CML ASCO 2006 Conference Summaries.
6. ^ Else M, Ruchlemer R, Osuji N (2005). "Long remissions in hairy cell leukemia with purine analogs: a report of 219 patients with a median follow-up of 12.5 years". Cancer 104 (11): 2442–8. doi:10.1002/cncr.21447. PMID 16245328. 
7. ^ Matutes, Estella. (1998) "T-cell prolymphocytic leukemia, a rare variant of mature post-thymic T-cell leukemias, has distinct clinical and laboratory characteristics and a poor prognosis." Cancer Control Journal Volume 5 Number 1.
8. ^ Valbuena JR, Herling M, Admirand JH, Padula A, Jones D, Medeiros LJ (March 2005). "T-cell prolymphocytic leukemia involving extramedullary sites". Am. J. Clin. Pathol. 123 (3): 456–64. doi:10.1309/93P4-2RNG-5XBG-3KBE. PMID 15716243. http://www.medscape.com/viewarticle/501092. 
9. ^ Reference list is found at image description page in Wikimedia Commons
10. ^ ^{a b} Ross JA, Kasum CM, Davies SM, Jacobs DR, Folsom AR, Potter JD (August 2002). "Diet and risk of leukemia in the Iowa Women's Health Study". Cancer Epidemiol. Biomarkers Prev. 11 (8): 777–81. PMID 12163333. http://cebp.aacrjournals.org/content/11/8/777.long. 
11. ^ ^{a b c d e f} Wiernik, Peter H. (2001). Adult leukemias. New York: B. C. Decker. pp. 3–15. ISBN 1-55009-111-5. 
12. ^ ^{a b} Robinette, Martin S.; Cotter, Susan; Van de Water (2001). Quick Look Series in Veterinary Medicine: Hematology. Teton NewMedia. p. 105. ISBN 1-893441-36-9. 
13. ^ Stass, Sanford A.; Schumacher, Harold R.; Rock, William R. (2000). Handbook of hematologic pathology. New York, N.Y: Marcel Dekker. pp. 193–194. ISBN 0-8247-0170-4. 
14. ^ ^{a b c d} Non-Ionizing Radiation, Part 1: Static and Extremely Low-Frequency (ELF) Electric and Magnetic Fields (IARC Monographs on the Evaluation of the Carcinogenic Risks). Geneva: World Health Organisation. 2002. pp. 332–333, 338. ISBN 92-832-1280-0. http://monographs.iarc.fr/ENG/Monographs/vol80/index.php. 
15. ^ "WHO | Electromagnetic fields and public health". http://www.who.int/mediacentre/factsheets/fs322/en/index.html. Retrieved 2009-02-18. 
16. ^ ^{a b c} Fausel C (October 2007). "Targeted chronic myeloid leukemia therapy: seeking a cure". J Manag Care Pharm 13 (8 Suppl A): 8–12. PMID 17970609. http://www.amcp.org/data/jmcp/pages%208-12.pdf. 
17. ^ ^{a b c d} Dearden CE, Matutes E, Cazin B (September 2001). "High remission rate in T-cell prolymphocytic leukemia with CAMPATH-1H". Blood 98 (6): 1721–6. doi:10.1182/blood.V98.6.1721. PMID 11535503. http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=11535503. 
18. ^ "WHO Disease and injury country estimates". World Health Organization. 2009. http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html. Retrieved 2009-11-11. 
19. ^ ^{a b c} Mathers, Colin D, Cynthia Boschi-Pinto, Alan D Lopez and Christopher JL Murray (2001). "Cancer incidence, mortality and survival by site for 14 regions of the world.". Global Programme on Evidence for Health Policy Discussion Paper No. 13 (World Health Organization). http://www.who.int/entity/healthinfo/paper13.pdf. 
20. ^ ^{a b c} "Leukemia Facts & Statistics." The Leukemia & Lymphoma Society. Accessed 2009-07-02.
21. ^ Horner MJ, Ries LAG, Krapcho M, Neyman N, et al. (eds).. "SEER Cancer Statistics Review, 1975–2006". Surveillance Epidemiology and End Results (SEER). Bethesda, MD: National Cancer Institute. http://seer.cancer.gov/csr/1975_2006/. Retrieved 2009-11-03. "Table 1.4: Age-Adjusted SEER Incidence and U.S. Death Rates and 5-Year Relative Survival Rates By Primary Cancer Site, Sex and Time Period" 

External links

• Leukemia at the Open Directory Project

v • d • e Hematological malignancy/leukemia histology (ICD-O 9590-9989, C81-C96, 200-208) Lymphoid/Lymphoproliferative, Lymphomas/Lymphoid leukemias (9590-9739, 9800-9839) B cell (lymphoma, leukemia) (most CD19, CD20) By development/ marker TdT+ ALL (Precursor B acute lymphoblastic leukemia/lymphoma) CD5+ naive B cell (CLL/SLL) mantle zone (Mantle cell) CD22+ Prolymphocytic · CD11c (Hairy cell leukemia) CD79a+ germinal center/follicular B cell (Follicular, Burkitt's, GCB-DLBCL) marginal zone/marginal-zone B cell (Splenic marginal zone, MALT, Nodal marginal zone) RS (CD15+,CD30+) Classic Hodgkin's lymphoma (Nodular sclerosis) · CD20 (Nodular lymphocyte predominant Hodgkin's lymphoma) PCDs/PP (CD38+/CD138+) see immunoproliferative immunoglobulin disorders By infection KSHV (Primary effusion) · EBV (Lymphomatoid granulomatosis, Post-transplant lymphoproliferative disorder) · HIV (AIDS-related lymphoma) · Helicobacter pylori (MALT lymphoma) T/NK T cell (lymphoma, leukemia) (most CD3, CD4, CD8) By development/ marker TdT+: ALL (Precursor T acute lymphoblastic leukemia/lymphoma) prolymphocyte (Prolymphocytic) CD30+ (Anaplastic large cell, Lymphomatoid papulosis) By location/peripheral Cutaneous (Mycosis fungoides, Sézary's disease) · Hepatosplenic · Angioimmunoblastic · Enteropathy-associated T-cell lymphoma By infection HTLV-1 (Adult T-cell leukemia/lymphoma) NK cell/ (most CD56) Aggressive NK-cell leukemia · Blastic NK cell lymphoma T or NK EBV (Extranodal NK-T-cell lymphoma) · Large granular lymphocytic leukemia Lymphoid+myeloid Acute biphenotypic leukaemia Lymphocytosis Lymphoproliferative disorders (X-linked lymphoproliferative disease, Autoimmune lymphoproliferative syndrome) · Leukemoid reaction · Pseudolymphoma lymphocyte navs: cells/physio, immunodeficiency/immunoproliferative immunoglobulin/neoplasia, proc

v • d • e Myeloid Hematological malignancy/leukemia histology (ICD-O 9590-9989, C81-C96, 200-208) CFU-GM/ and other granulocytes CFU-GM Myelocyte AML: Acute myeloblastic leukemia (M0, M1, M2), APL/M3 MP (Chronic neutrophilic leukemia) Monocyte AML (AMoL/M5, Myeloid dendritic cell leukemia) CML (Philadelphia chromosome, Accelerated phase chronic myelogenous leukemia) Myelomonocyte AML (M4) MD-MP (Juvenile myelomonocytic leukemia, Chronic myelomonocytic leukemia) Other Histiocytosis CFU-Baso AML (Acute basophilic) CFU-Eos AML (Acute eosinophilic) MP (Chronic eosinophilic leukemia/Hypereosinophilic syndrome) MEP CFU-Meg AML (AMKL/M7) MP (Essential thrombocytosis) CFU-E AML (Erythroleukemia/M6) MP (Polycythemia vera) MD (Refractory anemia, Refractory anemia with excess of blasts, Chromosome 5q deletion syndrome, Sideroblastic anemia, Paroxysmal nocturnal hemoglobinuria, Refractory cytopenia with multilineage dysplasia) CFU-Mast Mastocytoma (Mast cell leukemia, Mast cell sarcoma, Systemic mastocytosis) Multiple/unknown AML (Acute panmyelosis with myelofibrosis, Myeloid sarcoma) · MP (Myelofibrosis) · Acute biphenotypic leukaemia myeloid navs: cells/physio, disease of RBCs+megakaryocytes/monocytes+granulocytes/neoplasia, symptoms+signs/eponymous

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Dansk (Danish)
n. - leukæmi

Nederlands (Dutch)
leukemie, bloedkanker

Français (French)
n. - leucémie

Deutsch (German)
n. - Leukämie

Ελληνική (Greek)
n. - λευχαιμία

Italiano (Italian)
leucemia

Português (Portuguese)
n. - leucemia (f) (Patol.)

Русский (Russian)
лейкемия

Español (Spanish)
n. - leucemia, cáncer de la sangre

Svenska (Swedish)
n. - leukemi, blodcancer

中文（简体）(Chinese (Simplified))
白血病

中文（繁體）(Chinese (Traditional))
n. - 白血病

한국어 (Korean)
n. - 백혈병

日本語 (Japanese)
n. - 白血病

العربيه (Arabic)
‏(الاسم) اللوكيميا, إبيضاض الدم مرض, سرطان الدم‏

עברית (Hebrew)
n. - ‮סרטן הדם, לוקמיה‬

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