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Leukemia
ICD-10 C91-C95
ICD-9 208.9
OMIM [1]
DiseasesDB 7431
MedlinePlus [2]
eMedicine /
MeSH {{{MeshNumber}}}


Leukemia (Template:Lang-en-GB) (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.

ClassificationEdit

Leukemia is clinically and pathologically subdivided into several 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:

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.

SymptomsEdit

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 and risk factorsEdit

There is no single known cause for all of the different types of leukemia. The different leukemias likely have different causes. Known causes include natural and artificial ionizing radiation, viruses such as Human T-lymphotropic virus, and some chemicals, notably benzene and alkylating chemotherapy agents for previous malignancies.[9][10][11] Use of tobacco is associated with a small increase in the risk of developing acute myeloid leukemia in adults.[9] A few cases of maternal-fetal transmission have been reported.[9]

Leukemia, like other cancers, results from somatic mutations in the DNA which activate oncogenes or deactivate tumor 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 to be influenced by genetic factors. Cohort and case-control studies have linked exposure to petrochemicals, such as benzene, and hair dyes to the development of some forms of leukemia.

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.[9] 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.[9]

In addition to these genetic issues, people with chromosomal abnormalities or certain other genetic conditions have a greater risk of leukemia.[10] 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. [9]

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.[12] 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.[12] However, the report also says that methodological weaknesses and biases in these studies have likely caused the risk to be overstated.[12] No evidence for a relationship to leukemia or an other form of malignancy in adults has been demonstrated.[12] 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.[13]

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 Edit

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)Edit

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)Edit

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:

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)Edit

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)Edit

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.[14] 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,[14] 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.[14]

Hairy cell leukemia (HCL)Edit

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) Edit

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.[15]

T-cell prolymphocytic leukemia is difficult to treat, and it does not respond to most available chemotherapeutic drugs.[15] 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.[15]

Some patients who successfully respond to treatment also undergo stem cell transplantation to consolidate the response.[15]

Research Edit

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.

Epidemiology Edit

In 2000, approximately 256,000 children and adults around the world developed a form of leukemia, and 209,000 died from it.[16] 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.[16] 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.[16]

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.[17]

Among children with some form of cancer, about a third have a type of leukemia, most commonly acute lymphoblastic leukemia.[17] 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.[17]

See alsoEdit

ReferencesEdit

  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.
  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.
  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, et al. (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.
  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.
  9. 9.0 9.1 9.2 9.3 9.4 9.5 Wiernik, Peter H. (2001). Adult leukemias, 3–15, New York: B. C. Decker.
  10. 10.0 10.1 Robinette, Martin S.; Cotter, Susan; Van de Water (2001). Quick Look Series in Veterinary Medicine: Hematology, 105, Teton NewMedia.
  11. Stass, Sanford A.; Schumacher, Harold R.; Rock, William R. (2000). Handbook of hematologic pathology, 193–194, New York, N.Y: Marcel Dekker.
  12. 12.0 12.1 12.2 12.3 (2002) Non-Ionizing Radiation, Part 1: Static and Extremely Low-Frequency (ELF) Electric and Magnetic Fields (IARC Monographs on the Evaluation of the Carcinogenic Risks), 332–333, 338, Geneva: World Health Organisation.
  13. WHO | Electromagnetic fields and public health. URL accessed on 2009-02-18.
  14. 14.0 14.1 14.2 Fausel C (October 2007). Targeted chronic myeloid leukemia therapy: seeking a cure. J Manag Care Pharm 13 (8 Suppl A): 8–12.
  15. 15.0 15.1 15.2 15.3 Dearden CE, Matutes E, Cazin B, et al. (September 2001). High remission rate in T-cell prolymphocytic leukemia with CAMPATH-1H. Blood 98 (6): 1721–6.
  16. 16.0 16.1 16.2 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..
  17. 17.0 17.1 17.2 "Leukemia Facts & Statistics." The Leukemia & Lymphoma Society. Accessed on July 2 2009.

External linksEdit

Template:Lymphoid malignancy Template:Myeloid malignancy


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