Leukemia 18539 226072779 2008-07-16T18:31:27Z MattieTK 434929 Reverted edits by [[Special:Contributions/209.23.137.194|209.23.137.194]] to last version by ClueBot (using [[WP:HG|Huggle]]) {{DiseaseDisorder infobox | Name = Leukaemia | ICD10 = {{ICD10|C|91||c|81}}-{{ICD10|C|95||c|81}} | ICD9 = {{ICD9|208.9}} | ICDO = 9800-9940 | Image = acute_leukemia-ALL.jpg | Caption = A Wright's stained bone marrow aspirate smear of patient with precursor B-cell acute lymphoblastic leukemia.| OMIM = | MedlinePlus = | eMedicineSubj = | eMedicineTopic = | DiseasesDB = 7431 | MeshID = D007938 | }} '''Leukemia''' or '''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 [[Cell (biology)|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 malignancy|hematological neoplasms]]. ==Classification== Leukemia is clinically and pathologically subdivided into several large groups. The first division is between its ''[[Acute (medical)|acute]]'' and ''[[chronic (medicine)|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. 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 [[United States|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. Central nervous system (CNS) involvement is uncommon, although the disease can occasionally cause cranial nerve palsies. * ''[[Chronic leukemia]]'' is distinguished by the excessive build up of relatively mature, but still abnormal, 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. 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. Additionally, the diseases are subdivided according to which kind of blood cell is affected. This split divides leukemias into lymphoblastic or ''[[lymphocytic leukemia]]s'' and myeloid or ''[[myelogenous leukemia]]s'': * In lymphoblastic or ''[[lymphocytic leukemia]]s'', the cancerous change took place in a type of marrow cell that normally goes on to form [[lymphocyte]]s. * In myeloid or ''[[myelogenous leukemia]]s'', the cancerous change took place in a [[myeloid cells|type of marrow cell]] that normally goes on to form red cells, some types of white cells, and [[platelets]]. Combining these two classifications provides a total of four main categories: {| class="wikitable" |+Four major kinds of leukemia ! Cell type !! Acute !! Chronic |- | '''Lymphocytic leukemia''' <br />(or "lymphoblastic") || [[Acute lymphocytic leukemia]] (ALL) || [[Chronic lymphocytic leukemia]] (CLL) |- | '''Myelogenous leukemia''' <br />(also "myeloid" or "nonlymphocytic") || [[Acute myeloid leukemia|Acute myelogenous leukemia]] (AML) || [[Chronic myelogenous leukemia]] (CML) |} Within these main categories, there are typically several subcategories. Finally, [[hairy cell leukemia]] is 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.<ref>[http://www.accessmedicine.com/content.aspx?aID=65842 Harrison's Principles of Internal Medicine, 16th Edition,] Chapter 97. Malignancies of Lymphoid Cells. Clinical Features, Treatment, and Prognosis of Specific Lymphoid Malignancies.</ref> * ''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%.<ref>[http://seer.cancer.gov/statfacts/html/clyl.html Finding Cancer Statistics » Cancer Stat Fact Sheets »Chronic Lymphocytic Leukemia] National Cancer Institute</ref> It is incurable, but there are many effective treatments. * ''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%.<ref>{{cite journal |author=Colvin GA, Elfenbein GJ |title=The latest treatment advances for acute myelogenous leukemia |journal=Med Health R I |volume=86 |issue=8 |pages=243–6 |year=2003 |pmid=14582219 |doi=}}</ref> * ''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%.<ref>[http://www.medscape.com/viewarticle/536049 Patients with Chronic Myelogenous Leukemia Continue to Do Well on Imatinib at 5-Year Follow-Up] Medscape Medical News 2006</ref><ref>[http://professional.cancerconsultants.com/conference_asco_2006.aspx?id=37519 Updated Results of Tyrosine Kinase Inhibitors in CML] ASCO 2006 Conference Summaries</ref> * ''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.<ref name="pmid16245328">{{cite journal |author=Else M, Ruchlemer R, Osuji N, ''et al'' |title=Long remissions in hairy cell leukemia with purine analogs: a report of 219 patients with a median follow-up of 12.5 years |journal=[[Cancer]] |volume=104 |issue=11 |pages=2442–8 |year=2005 |pmid=16245328 |doi=10.1002/cncr.21447}}</ref> ==Symptoms== 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 [[platelet]]s, which are important in the [[Coagulation of human blood|blood clotting]] process. This means people with leukemia may become [[purpura|bruised]], [[hemorrhage|bleed]] excessively, or develop pinprick bleeds ([[petechia]]e). [[White blood cell]]s, which are involved in fighting [[pathogen]]s, 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. Finally, the red blood cell deficiency leads to [[anemia]], which may cause [[dyspnea]]. All symptoms can be attributed to other diseases. Some other related symptoms: {{div col}} * Fever, chills, night sweats and other flu-like symptoms * Weakness and fatigue * Swollen or bleeding gums * Neurological symptoms ([[headache]]s) * Enlarged [[liver]] and [[spleen]] * Frequent [[infection]] * Bone pain * Joint pain * Dizziness * Nausea * Swollen [[tonsils]] * [[Diarrhea]] * Paleness * [[Malaise]] * Unintentional [[Weight_loss#Unintentional_weight_loss | weight loss]] {{div col end}} 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]]. ==Diagnosis== [[Diagnosis]] requires [[blood test]]s to look for an abnormal number of white blood cells, and a [[bone marrow examination]] to look for abnormal numbers or forms of cells in the bone marrow. ==Causes and risk factors== There is no single known cause for all of the different types of leukemia. The different leukemias likely have different causes, and very little is certain about what causes them. Researchers have strong suspicions about four possible causes: * natural or artificial ionizing radiation * certain kinds of chemicals * some viruses * genetic predispositions Leukemia, like other cancers, results from [[somatic mutation]]s in the [[DNA]] which activate [[oncogene]]s or deactivate [[tumor suppressor gene]]s, and disrupt the regulation of cell death, differentiation or division. These mutations may occur spontaneously or as a result of exposure to [[ionizing radiation|radiation]] or [[carcinogen]]ic 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 dye]]s to the development of some forms of leukemia. [[virus (biology)|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, a CNN Health report says children may be offered limited protection against leukemia by exposure to certain germs. [[Fanconi anemia]] is also a risk factor for developing [[Acute myeloid leukemia|acute myelogenous leukemia]]. 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 options for leukemia by type == ===Acute lymphoblastic leukemia (ALL)=== {{See|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). 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'' to eliminate any remaining leukemia cells. This typically requires one to three months in adults and four to eight months in children. 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. 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 two years. * Alternatively, ''[[allogeneic bone marrow transplantation]]'' may be appropriate for high-risk or relapsed patients. ===Chronic lymphocytic leukemia (CLL)=== {{See|Chronic lymphocytic leukemia#Treatment}} '''Decision to treat'''<br> [[Hematologist]]s 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 node]]s or [[spleen]] * an increase in the rate of [[lymphocyte]] production '''Typical treatment approach'''<br> CLL is probably incurable by present treatments. The primary chemotherapeutic plan is [[polytherapy|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 [[Warm autoimmune hemolytic anemia|immunohemolytic anemia]] or [[Idiopathic thrombocytopenic purpura|immune-mediated thrombocytopenia]]. In resistant cases, [[monotherapy|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)=== {{See|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 (medicine)|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)=== {{See|Chronic myelogenous leukemia#Treatment}} There are many possible treatments for CML, but the standard of care for newly diagnosed patients is [[imatinib]] (Gleevec) therapy.<ref name="pmid17970609">{{cite journal |author=Fausel C |title=Targeted chronic myeloid leukemia therapy: seeking a cure |journal=J Manag Care Pharm |volume=13 |issue=8 Suppl A |pages=8–12 |year=2007 |month=October |pmid=17970609 |doi= |url=http://www.amcp.org/data/jmcp/pages%208-12.pdf }}</ref> Compared to most anti-cancer drugs, it has relatively few side effects and can be taken [[oral]]ly at home. With this drug, more than 90% of patients will be able to keep the disease in check for at least five years,<ref name="pmid17970609"/> 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.<ref name="pmid17970609"/> ===Hairy cell leukemia (HCL)=== {{See|Hairy cell leukemia#Treatment}} '''Decision to treat'''<br> 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&nbsp;K/µL), frequent infections, unexplained bruises, anemia, or fatigue that is significant enough to disrupt the patient's everyday life. '''Typical treatment approach'''<br> 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. == 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. == Epidemiology == As of 1998, it is estimated that each year, approximately 30,800 individuals will be diagnosed with leukemia in the United States and 21,700 individuals will die of the disease.<ref>{{cite web|url=http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&uid=12712476&cmd=showdetailview&indexed=google|title=Trends in leukemia incidence and survival in the United States (1973-1998)}}</ref> ==See also== *[[Hematologic diseases]] ==References== {{reflist}} ==External links== '''Images of leukemias''' *[http://www.healthsystem.virginia.edu/internet/hematology/HessIDB/stages-of-acute-leukemia.cfm UVA Healthsystem] -- Images of acute leukemias by stage '''Research organizations''' *[http://www.tacl.us/ The Therapeutic Advances in Childhood Leukemia (TACL) Consortium] -- US research group *[http://atlasgeneticsoncology.org/Educ/Hempat_e.html "Chromosomes, Leukaemias, Solid Tumors, Hereditary Cancers"] in AtlasGeneticsOncology. 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