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Wikipedia

Leukemia

January 22, 2023

For the journal, see Leukemia (journal). For animal diseases, see Leucosis.

Leukemia (also spelled leukaemia and pronounced /luːˈkiːmiːə/[1] loo-KEE-mee-ə) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells.[9] These blood cells are not fully developed and are called blasts or leukemia cells.[2] Symptoms may include bleeding and bruising, bone pain, fatigue, fever, and an increased risk of infections.[2] These symptoms occur due to a lack of normal blood cells.[2] Diagnosis is typically made by blood tests or bone marrow biopsy.[2]

Leukemia
Other namesLeukaemia
A Wright's stained bone marrow aspirate smear from a person with B-cell acute lymphoblastic leukemia.
Pronunciation
SpecialtyHematology and oncology
SymptomsBleeding, bruising, fatigue, fever, increased risk of infections[2]
Usual onsetAll ages,[3] most common in 60s and 70s.[4] It is the most common malignant cancer in children, but the cure rates are also higher for them.
CausesInherited and environmental factors[5]
Risk factorsSmoking, family history, ionizing radiation, some chemicals, prior chemotherapy, Down syndrome.[3][5]
Diagnostic methodBlood tests, bone marrow biopsy[2]
TreatmentChemotherapy, radiation therapy, targeted therapy, bone marrow transplant, supportive care[3][6]
PrognosisFive-year survival rate 57% (U.S.)[4]
Frequency2.3 million (2015)[7]
Deaths353,500 (2015)[8]

The exact cause of leukemia is unknown.[5] A combination of genetic factors and environmental (non-inherited) factors are believed to play a role.[5] Risk factors include smoking, ionizing radiation, petrochemicals (such as benzene), prior chemotherapy, and Down syndrome.[5][3] People with a family history of leukemia are also at higher risk.[3] There are four main types of leukemia—acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML)—as well as a number of less common types.[3][10] Leukemias and lymphomas both belong to a broader group of tumors that affect the blood, bone marrow, and lymphoid system, known as tumors of the hematopoietic and lymphoid tissues.[11][12]

Treatment may involve some combination of chemotherapy, radiation therapy, targeted therapy, and bone marrow transplant, in addition to supportive care and palliative care as needed.[3][6] Certain types of leukemia may be managed with watchful waiting.[3] The success of treatment depends on the type of leukemia and the age of the person. Outcomes have improved in the developed world.[10] Five-year survival rate is 65% in the United States.[4] In children under 15 in first-world countries, the five-year survival rate is greater than 60% or even 90%, depending on the type of leukemia.[13] In children with acute leukemia who are cancer-free after five years, the cancer is unlikely to return.[13]

In 2015, leukemia was present in 2.3 million people worldwide and caused 353,500 deaths.[7][8] In 2012 it newly developed in 352,000 people.[10] It is the most common type of cancer in children, with three-quarters of leukemia cases in children being the acute lymphoblastic type.[3] However, over 90% of all leukemias are diagnosed in adults, with CLL and AML being most common in adults.[3][14] It occurs more commonly in the developed world.[10]

Classification

Four major kinds of leukemia
Cell type Acute Chronic
Lymphocytic leukemia
(or "lymphoblastic")		 Acute lymphoblastic leukemia
(ALL)		 Chronic lymphocytic leukemia
(CLL)
Myelogenous leukemia
("myeloid" or "nonlymphocytic")		 Acute myelogenous leukemia
(AML or myeloblastic)		 Chronic myelogenous leukemia
(CML)
An explanation of acute leukemia

General classification

Clinically and pathologically, leukemia is subdivided into a variety of large groups. The first division is between its acute and chronic forms:[15]

  • Acute leukemia is characterized by a rapid increase in the number of immature blood cells. The crowding that results from such cells makes the bone marrow unable to produce healthy blood cells resulting in low hemoglobin and low platelets. Immediate treatment is required in acute leukemia because of 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 characterized by the excessive buildup 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, resulting in many abnormal white blood cells. 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 occur in any age group.

Additionally, the diseases are subdivided according to which kind of blood cell is affected. This divides leukemias into lymphoblastic or lymphocytic leukemias and myeloid or myelogenous leukemias:[15]

Combining these two classifications provides a total of four main categories. Within each of these main categories, there are typically several subcategories. Finally, some rarer types are usually considered to be outside of this classification scheme.[15][16]

Specific types

Pre-leukemia

Signs and symptoms

 
Common symptoms of chronic or acute leukemia[33]

The most common symptoms in children are easy bruising, pale skin, fever, and an enlarged spleen or liver.[34]

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).[35]

White blood cells, which are involved in fighting pathogens, may be suppressed or dysfunctional. This could cause the person'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 people experience frequent infection, ranging from infected tonsils, sores in the mouth, or diarrhea to life-threatening pneumonia or opportunistic infections.[36]

Finally, the red blood cell deficiency leads to anemia, which may cause dyspnea and pallor.[37]

Some people experience other symptoms, such as fevers, chills, night sweats, weakness in the limbs, feeling fatigued and other common flu-like symptoms. Some people experience nausea or a feeling of fullness due to an enlarged liver and spleen; this can result in unintentional weight loss. Blasts affected by the disease may come together and become swollen in the liver or in the lymph nodes causing pain and leading to nausea.[38]

If the leukemic cells invade the central nervous system, then neurological symptoms (notably headaches) can occur. Uncommon neurological symptoms like migraines, seizures, or coma can occur as a result of brain stem pressure. 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 characteristic high white blood cell count that presents in most affected people before treatment. The high number of white blood cells is apparent when a blood sample is viewed under a microscope, with the extra white blood cells frequently being immature or dysfunctional. The excessive number of cells can also interfere with the level of other cells, causing further harmful imbalance in the blood count.[39]

Some people diagnosed with leukemia 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 that disrupt the normal production of blood cells, but they remain in the marrow instead of entering the bloodstream, where they would be visible in a blood test. For a person with aleukemia, 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.[40]

Causes

There is no single known cause for any of the different types of leukemias. The few known causes, which are not generally factors within the control of the average person, account for relatively few cases.[41] The cause for most cases of leukemia is unknown. The different leukemias likely have different causes.[42]

Leukemia, like other cancers, results from mutations in the DNA. Certain mutations can trigger 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.[43]

Among adults, the known causes are natural and artificial ionizing radiation and petrochemicals, notably benzene and alkylating chemotherapy agents for previous malignancies.[44][45][46] Use of tobacco is associated with a small increase in the risk of developing acute myeloid leukemia in adults.[44] Cohort and case-control studies have linked exposure to some petrochemicals and hair dyes to the development of some forms of leukemia. Diet has very limited or no effect, although eating more vegetables may confer a small protective benefit.[41]

Viruses have also been linked to some forms of leukemia. For example, human T-lymphotropic virus (HTLV-1) causes adult T-cell leukemia.[47]

A few cases of maternal-fetal transmission (a baby acquires leukemia because its mother had leukemia during the pregnancy) have been reported.[44] Children born to mothers who use fertility drugs to induce ovulation are more than twice as likely to develop leukemia during their childhoods than other children.[48]

In a recent systematic review and meta-analysis, a statistically significant association was detected between neonatal phototherapy and any type of leukemia, and myeloid leukemia. However, it is still questionable whether phototherapy is genuinely the cause of cancer or simply a result of the same underlying factors that gave rise to cancer. [49]

Radiation

Large doses of Sr-90 emission from nuclear reactor accidents, nicknamed bone seeker increases the risk of bone cancer and leukemia in animals and is presumed to do so in people.[50]

Genetic conditions

Some people have a genetic predisposition towards developing leukemia. This predisposition is demonstrated by family histories and twin studies.[44] The affected people may have a single gene or multiple genes in common. In some cases, families tend to develop the same kinds of leukemia as other members; in other families, affected people may develop different forms of leukemia or related blood cancers.[44]

In addition to these genetic issues, people with chromosomal abnormalities or certain other genetic conditions have a greater risk of leukemia.[45] For example, people with Down syndrome have a significantly increased risk of developing forms of acute leukemia (especially acute myeloid leukemia), and Fanconi anemia is a risk factor for developing acute myeloid leukemia.[44] Mutation in SPRED1 gene has been associated with a predisposition to childhood leukemia.[51]

Chronic myelogenous leukemia is associated with a genetic abnormality called the Philadelphia translocation; 95% of people with CML carry the Philadelphia mutation, although this is not exclusive to CML and can be observed in people with other types of leukemia.[52][53][54][55]

Non-ionizing radiation

Whether or not 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.[56] They concluded that there is limited evidence that high levels of ELF magnetic (but not electric) fields might cause some cases of childhood leukemia.[56] No evidence for a relationship to leukemia or another form of malignancy in adults has been demonstrated.[56] 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 4.9% of the total incidence of childhood leukemia for that year (about 0.03 to 0.9% of all leukemias).[57]

Diagnosis

 
The increase in white blood cells in leukemia.

Diagnosis is usually based on repeated complete blood counts and a bone marrow examination following observations of the symptoms. Sometimes, blood tests may not show that a person has leukemia, especially in the early stages of the disease or during remission. A lymph node biopsy can be performed to diagnose certain types of leukemia in certain situations.[58]

Following diagnosis, blood chemistry tests can be used to determine the degree of liver and kidney damage or the effects of chemotherapy on the person. When concerns arise about other damages due to leukemia, doctors may use an X-ray, MRI, or ultrasound. These can potentially show leukemia's effects on such body parts as bones (X-ray), the brain (MRI), or the kidneys, spleen, and liver (ultrasound). CT scans can be used to check lymph nodes in the chest, though this is uncommon.[59]

Despite the use of these methods to diagnose whether or not a person has leukemia, many people have not been diagnosed because many of the symptoms are vague, non-specific, and can refer to other diseases. For this reason, the American Cancer Society estimates that at least one-fifth of the people with leukemia have not yet been diagnosed.[40]

Treatment

Most forms of leukemia are treated with pharmaceutical medication, typically combined into a multi-drug chemotherapy regimen. Some are also treated with radiation therapy. In some cases, a bone marrow transplant is effective.

Acute lymphoblastic

Further information: Acute lymphoblastic leukemia § Treatment

Management of ALL is directed towards 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.[clarification needed] 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. People with low- to average-risk ALL receive therapy with antimetabolite drugs such as methotrexate and 6-mercaptopurine (6-MP). People who are high-risk receive higher drug doses of these drugs, plus additional drugs.
  • CNS prophylaxis (preventive therapy) to stop cancer from spreading to the brain and nervous system in high-risk people. 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 people.[60]

Chronic lymphocytic

Further information: Chronic lymphocytic leukemia § Treatment

Decision to treat

Hematologists base CLL treatment on both the stage and symptoms of the individual person. A large group of people with CLL 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:[citation needed]

Treatment approach

Most CLL cases are incurable by present treatments, so treatment is directed towards suppressing the disease for many years, rather than curing it. 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,[62] pentostatin, or cladribine may be successful. Younger and healthier people may choose allogeneic or autologous bone marrow transplantation in the hope of a permanent cure.[63]

Acute myelogenous

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 person 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.[64]

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 of chemotherapy with additional drugs. By contrast, maintenance treatment involves drug doses that are lower than those administered during the induction phase.[65]

Chronic myelogenous

Further information: Chronic myelogenous leukemia § Treatment

There are many possible treatments for CML, but the standard of care for newly diagnosed people is imatinib (Gleevec) therapy.[66] 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 people will be able to keep the disease in check for at least five years,[66] so that CML becomes a chronic, manageable condition.

In a more advanced, uncontrolled state, when the person cannot tolerate imatinib, or if the person 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 people die from this procedure.[66]

Hairy cell

Further information: Hairy cell leukemia § Treatment

Decision to treat
People with hairy cell leukemia who are symptom-free typically do not receive immediate treatment. Treatment is generally considered necessary when the person 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 person's everyday life.[67]

Typical treatment approach
People 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.[68]

Other treatments include rituximab infusion or self-injection with Interferon-alpha. In limited cases, the person 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.[69]

T-cell prolymphocytic

Further information: T-cell prolymphocytic leukemia § Treatment

Most people with T-cell prolymphocytic leukemia, a rare and aggressive leukemia with a median survival of less than one year, require immediate treatment.[70]

T-cell prolymphocytic leukemia is difficult to treat, and it does not respond to most available chemotherapeutic drugs.[70] Many different treatments have been attempted, with limited success in certain people: 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.[70]

Some people who successfully respond to treatment also undergo stem cell transplantation to consolidate the response.[70]

Juvenile myelomonocytic

Further information: Juvenile myelomonocytic leukemia § Treatment

Treatment for juvenile myelomonocytic leukemia can include splenectomy, chemotherapy, and bone marrow transplantation.[71]

Teeth

Before dental work it is recommended that the person's physician be consulted. Dental work is recommended before chemotherapy or radiation therapy. Those in remission can be treated per normal.[72]

Prognosis

The success of treatment depends on the type of leukemia and the age of the person. Outcomes have improved in the developed world.[10] The average five-year survival rate is 65% in the United States.[4] In children under 15, the five-year survival rate is greater (60 to 85%), depending on the type of leukemia.[13] In children with acute leukemia who are cancer-free after five years, the cancer is unlikely to return.[13]

Outcomes depend on whether it is acute or chronic, the specific abnormal white blood cell type, the presence and severity of anemia or thrombocytopenia, the degree of tissue abnormality, the presence of metastasis and lymph node and bone marrow infiltration, the availability of therapies and the skills of the health care team. Treatment outcomes may be better when people are treated at larger centers with greater experience.[73]

Epidemiology

 
Deaths due to leukemia per million persons in 2012
  0-7
  8-13
  14–22
  23–29
  30–34
  35–39
  40–46
  47–64
  65–85
  86–132

In 2010, globally, approximately 281,500 people died of leukemia.[74] In 2000, approximately 256,000 children and adults around the world developed a form of leukemia, and 209,000 died from it.[75] 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.[75] 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.[75] Leukemia occurs more commonly in the developed world.[76]

United States

About 245,000 people in the United States are affected with some form of leukemia, including those that have achieved remission or cure. Rates from 1975 to 2011 have increased by 0.7% per year among children.[77] Approximately 44,270 new cases of leukemia were diagnosed in the year 2008 in the US.[78] 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.[79]

Among children with some form of cancer, about a third have a type of leukemia, most commonly acute lymphoblastic leukemia.[78] A type of leukemia is the second most common form of cancer in infants (under the age of 12 months) and the most common form of cancer in older children.[80] Boys are somewhat more likely to develop leukemia than girls, and white American children are almost twice as likely to develop leukemia than black American children.[80] 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.[78]

Race is a risk factor in the United States. Hispanics, especially those under the age of 20, are at the highest risk for leukemia, while whites, Native Americans, Asian Americans, and Alaska Natives are at higher risk than African Americans.[81]

More men than women are diagnosed with leukemia and die from the disease. Around 30 percent more men than women have leukemia.[82]

UK

Overall, leukemia is the eleventh most common cancer in the UK (around 8,600 people were diagnosed with the disease in 2011), and it is the ninth most common cause of cancer death (around 4,800 people died in 2012).[83]

History

 
Rudolf Virchow

Leukemia was first described by anatomist and surgeon Alfred-Armand-Louis-Marie Velpeau in 1827. A more complete description was given by pathologist Rudolf Virchow in 1845. Around ten years after Virchow's findings, pathologist Franz Ernst Christian Neumann found that the bone marrow of a deceased person with leukemia was colored "dirty green-yellow" as opposed to the normal red. This finding allowed Neumann to conclude that a bone marrow problem was responsible for the abnormal blood of people with leukemia.[84]

By 1900, leukemia was viewed as a family of diseases as opposed to a single disease. By 1947, Boston pathologist Sidney Farber believed from past experiments that aminopterin, a folic acid mimic, could potentially cure leukemia in children. The majority of the children with ALL who were tested showed signs of improvement in their bone marrow, but none of them was actually cured. This, however, led to further experiments.[85]

In 1962, researchers Emil J. Freireich, Jr. and Emil Frei III used combination chemotherapy to attempt to cure leukemia. The tests were successful with some people surviving long after the tests.[86]

Etymology

Observing an abnormally large number of white blood cells in a blood sample from a person, Virchow called the condition Leukämie in German, which he formed from the two Greek words leukos (λευκός), meaning "white", and haima (αἷμα), meaning "blood".[87]

Society and culture

According to Susan Sontag, leukemia was often romanticized in 20th-century fiction, portrayed as a joy-ending, clean disease whose fair, innocent and gentle victims die young or at the wrong time. As such, it was the cultural successor to tuberculosis, which held this cultural position until it was discovered to be an infectious disease.[88] The 1970 romance novel Love Story is an example of this romanticization of leukemia.[89]

In the United States, around $5.4 billion is spent on treatment a year.[90]

Research directions

Significant research into the causes, prevalence, diagnosis, treatment, and prognosis of leukemia is being performed. Hundreds of clinical trials are being planned or conducted at any given time.[91] Studies may focus on effective means of treatment, better ways of treating the disease, improving the quality of life for people, or appropriate care in remission or after cures.[citation needed]

In general, there are two types of leukemia research: clinical or translational research and basic research. Clinical/translational research focuses on studying the disease in a defined and generally immediately applicable way, such as testing a new drug in people. By contrast, basic science research studies the disease process at a distance, such as seeing whether a suspected carcinogen can cause leukemic changes in isolated cells in the laboratory or how the DNA changes inside leukemia cells as the disease progresses. The results from basic research studies are generally less immediately useful to people with the disease.[92]

Treatment through gene therapy is currently being pursued. One such approach used genetically modified T cells, known as chimeric antigen receptor T cells (CAR-T cells), to attack cancer cells. In 2011, a year after treatment, two of the three people with advanced chronic lymphocytic leukemia were reported to be cancer-free[93] and in 2013, three of five subjects who had acute lymphocytic leukemia were reported to be in remission for five months to two years.[94] Subsequent studies with a variety of CAR-T types continue to be promising.[95] As of 2018, two CAR-T therapies have been approved by the Food and Drug Administration. CAR-T treatment has significant side effects,[96] and loss of the antigen targeted by the CAR-T cells is a common mechanism for relapse.[95] The stem cells that cause different types of leukemia are also being researched.[97]

Pregnancy

Leukemia is rarely associated with pregnancy, affecting only about 1 in 10,000 pregnant women.[98] How it is handled depends primarily on the type of leukemia. Nearly all leukemias appearing in pregnant women are acute leukemias.[99] Acute leukemias normally require prompt, aggressive treatment, despite significant risks of pregnancy loss and birth defects, especially if chemotherapy is given during the developmentally sensitive first trimester.[98] Chronic myelogenous leukemia can be treated with relative safety at any time during pregnancy with Interferon-alpha hormones.[98] Treatment for chronic lymphocytic leukemias, which are rare in pregnant women, can often be postponed until after the end of the pregnancy.[98][99]

See also

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January 22, 2023
leukemia, journal, journal, animal, diseases, leucosis, also, spelled, leukaemia, pronounced, group, blood, cancers, that, usually, begin, bone, marrow, result, high, numbers, abnormal, blood, cells, these, blood, cells, fully, developed, called, blasts, leuke. For the journal see Leukemia journal For animal diseases see Leucosis Leukemia also spelled leukaemia and pronounced l uː ˈ k iː m iː e 1 loo KEE mee e is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells 9 These blood cells are not fully developed and are called blasts or leukemia cells 2 Symptoms may include bleeding and bruising bone pain fatigue fever and an increased risk of infections 2 These symptoms occur due to a lack of normal blood cells 2 Diagnosis is typically made by blood tests or bone marrow biopsy 2 LeukemiaOther namesLeukaemiaA Wright s stained bone marrow aspirate smear from a person with B cell acute lymphoblastic leukemia Pronunciation l uː ˈ k iː m iː e 1 SpecialtyHematology and oncologySymptomsBleeding bruising fatigue fever increased risk of infections 2 Usual onsetAll ages 3 most common in 60s and 70s 4 It is the most common malignant cancer in children but the cure rates are also higher for them CausesInherited and environmental factors 5 Risk factorsSmoking family history ionizing radiation some chemicals prior chemotherapy Down syndrome 3 5 Diagnostic methodBlood tests bone marrow biopsy 2 TreatmentChemotherapy radiation therapy targeted therapy bone marrow transplant supportive care 3 6 PrognosisFive year survival rate 57 U S 4 Frequency2 3 million 2015 7 Deaths353 500 2015 8 The exact cause of leukemia is unknown 5 A combination of genetic factors and environmental non inherited factors are believed to play a role 5 Risk factors include smoking ionizing radiation petrochemicals such as benzene prior chemotherapy and Down syndrome 5 3 People with a family history of leukemia are also at higher risk 3 There are four main types of leukemia acute lymphoblastic leukemia ALL acute myeloid leukemia AML chronic lymphocytic leukemia CLL and chronic myeloid leukemia CML as well as a number of less common types 3 10 Leukemias and lymphomas both belong to a broader group of tumors that affect the blood bone marrow and lymphoid system known as tumors of the hematopoietic and lymphoid tissues 11 12 Treatment may involve some combination of chemotherapy radiation therapy targeted therapy and bone marrow transplant in addition to supportive care and palliative care as needed 3 6 Certain types of leukemia may be managed with watchful waiting 3 The success of treatment depends on the type of leukemia and the age of the person Outcomes have improved in the developed world 10 Five year survival rate is 65 in the United States 4 In children under 15 in first world countries the five year survival rate is greater than 60 or even 90 depending on the type of leukemia 13 In children with acute leukemia who are cancer free after five years the cancer is unlikely to return 13 In 2015 leukemia was present in 2 3 million people worldwide and caused 353 500 deaths 7 8 In 2012 it newly developed in 352 000 people 10 It is the most common type of cancer in children with three quarters of leukemia cases in children being the acute lymphoblastic type 3 However over 90 of all leukemias are diagnosed in adults with CLL and AML being most common in adults 3 14 It occurs more commonly in the developed world 10 Contents 1 Classification 1 1 General classification 1 2 Specific types 1 3 Pre leukemia 2 Signs and symptoms 3 Causes 3 1 Radiation 3 2 Genetic conditions 3 3 Non ionizing radiation 4 Diagnosis 5 Treatment 5 1 Acute lymphoblastic 5 2 Chronic lymphocytic 5 2 1 Decision to treat 5 2 2 Treatment approach 5 3 Acute myelogenous 5 4 Chronic myelogenous 5 5 Hairy cell 5 6 T cell prolymphocytic 5 7 Juvenile myelomonocytic 5 8 Teeth 6 Prognosis 7 Epidemiology 7 1 United States 7 2 UK 8 History 8 1 Etymology 9 Society and culture 10 Research directions 11 Pregnancy 12 See also 13 References 14 External linksClassification EditFour major kinds of leukemia Cell type Acute ChronicLymphocytic leukemia or lymphoblastic Acute lymphoblastic leukemia ALL Chronic lymphocytic leukemia CLL Myelogenous leukemia myeloid or nonlymphocytic Acute myelogenous leukemia AML or myeloblastic Chronic myelogenous leukemia CML source source source source source source source source source source source source An explanation of acute leukemia General classification Edit Clinically and pathologically leukemia is subdivided into a variety of large groups The first division is between its acute and chronic forms 15 Acute leukemia is characterized by a rapid increase in the number of immature blood cells The crowding that results from such cells makes the bone marrow unable to produce healthy blood cells resulting in low hemoglobin and low platelets Immediate treatment is required in acute leukemia because of 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 characterized by the excessive buildup 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 resulting in many abnormal white blood cells 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 occur in any age group Additionally the diseases are subdivided according to which kind of blood cell is affected This divides leukemias into lymphoblastic or lymphocytic leukemias and myeloid or myelogenous leukemias 15 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 Within each of these main categories there are typically several subcategories Finally some rarer types are usually considered to be outside of this classification scheme 15 16 Specific types Edit Acute lymphoblastic leukemia ALL is the most common type of leukemia in young children It also affects adults especially those 65 and older Standard treatments involve chemotherapy and radiotherapy Subtypes include precursor B acute lymphoblastic leukemia precursor T acute lymphoblastic leukemia Burkitt s leukemia and acute biphenotypic leukemia While most cases of ALL occur in children 80 of deaths from ALL occur in adults 17 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 85 18 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 far more commonly in adults than in children and more commonly in men than women It is treated with chemotherapy The five year survival rate is 20 19 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 It is treated with imatinib Gleevec in United States Glivec in Europe or other drugs 20 The five year survival rate is 90 21 22 One subtype is chronic myelomonocytic leukemia Hairy cell leukemia HCL is sometimes considered a subset of chronic lymphocytic leukemia but does not fit neatly into this category About 80 of affected people are adult men No cases in children have been reported HCL is incurable but easily treatable Survival is 96 to 100 at ten years 23 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 24 Despite its overall rarity it is the most common type of mature T cell leukemia 25 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 cells or NK cells like hairy cell leukemia which involves solely B cells it is a rare and indolent not aggressive leukemia 26 Adult T cell leukemia is caused by human T lymphotropic virus HTLV a virus similar to HIV Like HIV HTLV infects CD4 T cells and replicates within them however unlike HIV it does not destroy them Instead HTLV immortalizes the infected T cells giving them the ability to proliferate abnormally Human T cell lymphotropic virus types I and II HTLV I II are endemic in certain areas of the world citation needed Clonal eosinophilias also called clonal hypereosinophilias are a group of blood disorders characterized by the growth of eosinophils in the bone marrow blood and or other tissues They may be pre cancerous or cancerous Clonal eosinophilias involve a clone of eosinophils i e a group of genetically identical eosinophils that all grew from the same mutated ancestor cell 27 These disorders may evolve into chronic eosinophilic leukemia or may be associated with various forms of myeloid neoplasms lymphoid neoplasms myelofibrosis or the myelodysplastic syndrome 28 29 27 Pre leukemia Edit Transient myeloproliferative disease also termed transient leukemia involves the abnormal proliferation of a clone of non cancerous megakaryoblasts The disease is restricted to individuals with Down syndrome or genetic changes similar to those in Down syndrome develops in a baby during pregnancy or shortly after birth and resolves within 3 months or in 10 of cases progresses to acute megakaryoblastic leukemia Transient myeloid leukemia is a pre leukemic condition 30 31 32 Signs and symptoms Edit Common symptoms of chronic or acute leukemia 33 The most common symptoms in children are easy bruising pale skin fever and an enlarged spleen or liver 34 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 35 White blood cells which are involved in fighting pathogens may be suppressed or dysfunctional This could cause the person 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 people experience frequent infection ranging from infected tonsils sores in the mouth or diarrhea to life threatening pneumonia or opportunistic infections 36 Finally the red blood cell deficiency leads to anemia which may cause dyspnea and pallor 37 Some people experience other symptoms such as fevers chills night sweats weakness in the limbs feeling fatigued and other common flu like symptoms Some people experience nausea or a feeling of fullness due to an enlarged liver and spleen this can result in unintentional weight loss Blasts affected by the disease may come together and become swollen in the liver or in the lymph nodes causing pain and leading to nausea 38 If the leukemic cells invade the central nervous system then neurological symptoms notably headaches can occur Uncommon neurological symptoms like migraines seizures or coma can occur as a result of brain stem pressure 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 characteristic high white blood cell count that presents in most affected people before treatment The high number of white blood cells is apparent when a blood sample is viewed under a microscope with the extra white blood cells frequently being immature or dysfunctional The excessive number of cells can also interfere with the level of other cells causing further harmful imbalance in the blood count 39 Some people diagnosed with leukemia 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 that disrupt the normal production of blood cells but they remain in the marrow instead of entering the bloodstream where they would be visible in a blood test For a person with aleukemia 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 40 Causes EditThere is no single known cause for any of the different types of leukemias The few known causes which are not generally factors within the control of the average person account for relatively few cases 41 The cause for most cases of leukemia is unknown The different leukemias likely have different causes 42 Leukemia like other cancers results from mutations in the DNA Certain mutations can trigger 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 43 Among adults the known causes are natural and artificial ionizing radiation and petrochemicals notably benzene and alkylating chemotherapy agents for previous malignancies 44 45 46 Use of tobacco is associated with a small increase in the risk of developing acute myeloid leukemia in adults 44 Cohort and case control studies have linked exposure to some petrochemicals and hair dyes to the development of some forms of leukemia Diet has very limited or no effect although eating more vegetables may confer a small protective benefit 41 Viruses have also been linked to some forms of leukemia For example human T lymphotropic virus HTLV 1 causes adult T cell leukemia 47 A few cases of maternal fetal transmission a baby acquires leukemia because its mother had leukemia during the pregnancy have been reported 44 Children born to mothers who use fertility drugs to induce ovulation are more than twice as likely to develop leukemia during their childhoods than other children 48 In a recent systematic review and meta analysis a statistically significant association was detected between neonatal phototherapy and any type of leukemia and myeloid leukemia However it is still questionable whether phototherapy is genuinely the cause of cancer or simply a result of the same underlying factors that gave rise to cancer 49 Radiation Edit Large doses of Sr 90 emission from nuclear reactor accidents nicknamed bone seeker increases the risk of bone cancer and leukemia in animals and is presumed to do so in people 50 Genetic conditions Edit Some people have a genetic predisposition towards developing leukemia This predisposition is demonstrated by family histories and twin studies 44 The affected people may have a single gene or multiple genes in common In some cases families tend to develop the same kinds of leukemia as other members in other families affected people may develop different forms of leukemia or related blood cancers 44 In addition to these genetic issues people with chromosomal abnormalities or certain other genetic conditions have a greater risk of leukemia 45 For example people with Down syndrome have a significantly increased risk of developing forms of acute leukemia especially acute myeloid leukemia and Fanconi anemia is a risk factor for developing acute myeloid leukemia 44 Mutation in SPRED1 gene has been associated with a predisposition to childhood leukemia 51 Chronic myelogenous leukemia is associated with a genetic abnormality called the Philadelphia translocation 95 of people with CML carry the Philadelphia mutation although this is not exclusive to CML and can be observed in people with other types of leukemia 52 53 54 55 Non ionizing radiation Edit Whether or not 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 56 They concluded that there is limited evidence that high levels of ELF magnetic but not electric fields might cause some cases of childhood leukemia 56 No evidence for a relationship to leukemia or another form of malignancy in adults has been demonstrated 56 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 9 of the total incidence of childhood leukemia for that year about 0 03 to 0 9 of all leukemias 57 Diagnosis Edit The increase in white blood cells in leukemia Diagnosis is usually based on repeated complete blood counts and a bone marrow examination following observations of the symptoms Sometimes blood tests may not show that a person has leukemia especially in the early stages of the disease or during remission A lymph node biopsy can be performed to diagnose certain types of leukemia in certain situations 58 Following diagnosis blood chemistry tests can be used to determine the degree of liver and kidney damage or the effects of chemotherapy on the person When concerns arise about other damages due to leukemia doctors may use an X ray MRI or ultrasound These can potentially show leukemia s effects on such body parts as bones X ray the brain MRI or the kidneys spleen and liver ultrasound CT scans can be used to check lymph nodes in the chest though this is uncommon 59 Despite the use of these methods to diagnose whether or not a person has leukemia many people have not been diagnosed because many of the symptoms are vague non specific and can refer to other diseases For this reason the American Cancer Society estimates that at least one fifth of the people with leukemia have not yet been diagnosed 40 Treatment EditMost forms of leukemia are treated with pharmaceutical medication typically combined into a multi drug chemotherapy regimen Some are also treated with radiation therapy In some cases a bone marrow transplant is effective Acute lymphoblastic Edit Further information Acute lymphoblastic leukemia Treatment Management of ALL is directed towards 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 clarification needed 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 People with low to average risk ALL receive therapy with antimetabolite drugs such as methotrexate and 6 mercaptopurine 6 MP People who are high risk receive higher drug doses of these drugs plus additional drugs CNS prophylaxis preventive therapy to stop cancer from spreading to the brain and nervous system in high risk people 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 people 60 Chronic lymphocytic Edit Further information Chronic lymphocytic leukemia Treatment Decision to treat Edit Hematologists base CLL treatment on both the stage and symptoms of the individual person A large group of people with CLL 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 citation needed 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 61 Treatment approach Edit Most CLL cases are incurable by present treatments so treatment is directed towards suppressing the disease for many years rather than curing it 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 62 pentostatin or cladribine may be successful Younger and healthier people may choose allogeneic or autologous bone marrow transplantation in the hope of a permanent cure 63 Acute myelogenous 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 person 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 64 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 of chemotherapy with additional drugs By contrast maintenance treatment involves drug doses that are lower than those administered during the induction phase 65 Chronic myelogenous Edit Further information Chronic myelogenous leukemia Treatment There are many possible treatments for CML but the standard of care for newly diagnosed people is imatinib Gleevec therapy 66 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 people will be able to keep the disease in check for at least five years 66 so that CML becomes a chronic manageable condition In a more advanced uncontrolled state when the person cannot tolerate imatinib or if the person 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 people die from this procedure 66 Hairy cell Edit Further information Hairy cell leukemia Treatment Decision to treat People with hairy cell leukemia who are symptom free typically do not receive immediate treatment Treatment is generally considered necessary when the person 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 person s everyday life 67 Typical treatment approach People 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 68 Other treatments include rituximab infusion or self injection with Interferon alpha In limited cases the person 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 69 T cell prolymphocytic Edit Further information T cell prolymphocytic leukemia Treatment Most people with T cell prolymphocytic leukemia a rare and aggressive leukemia with a median survival of less than one year require immediate treatment 70 T cell prolymphocytic leukemia is difficult to treat and it does not respond to most available chemotherapeutic drugs 70 Many different treatments have been attempted with limited success in certain people 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 70 Some people who successfully respond to treatment also undergo stem cell transplantation to consolidate the response 70 Juvenile myelomonocytic Edit Further information Juvenile myelomonocytic leukemia Treatment Treatment for juvenile myelomonocytic leukemia can include splenectomy chemotherapy and bone marrow transplantation 71 Teeth Edit Before dental work it is recommended that the person s physician be consulted Dental work is recommended before chemotherapy or radiation therapy Those in remission can be treated per normal 72 Prognosis EditThe success of treatment depends on the type of leukemia and the age of the person Outcomes have improved in the developed world 10 The average five year survival rate is 65 in the United States 4 In children under 15 the five year survival rate is greater 60 to 85 depending on the type of leukemia 13 In children with acute leukemia who are cancer free after five years the cancer is unlikely to return 13 Outcomes depend on whether it is acute or chronic the specific abnormal white blood cell type the presence and severity of anemia or thrombocytopenia the degree of tissue abnormality the presence of metastasis and lymph node and bone marrow infiltration the availability of therapies and the skills of the health care team Treatment outcomes may be better when people are treated at larger centers with greater experience 73 Epidemiology Edit Deaths due to leukemia per million persons in 2012 0 7 8 13 14 22 23 29 30 34 35 39 40 46 47 64 65 85 86 132 In 2010 globally approximately 281 500 people died of leukemia 74 In 2000 approximately 256 000 children and adults around the world developed a form of leukemia and 209 000 died from it 75 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 75 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 75 Leukemia occurs more commonly in the developed world 76 United States Edit About 245 000 people in the United States are affected with some form of leukemia including those that have achieved remission or cure Rates from 1975 to 2011 have increased by 0 7 per year among children 77 Approximately 44 270 new cases of leukemia were diagnosed in the year 2008 in the US 78 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 79 Among children with some form of cancer about a third have a type of leukemia most commonly acute lymphoblastic leukemia 78 A type of leukemia is the second most common form of cancer in infants under the age of 12 months and the most common form of cancer in older children 80 Boys are somewhat more likely to develop leukemia than girls and white American children are almost twice as likely to develop leukemia than black American children 80 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 78 Race is a risk factor in the United States Hispanics especially those under the age of 20 are at the highest risk for leukemia while whites Native Americans Asian Americans and Alaska Natives are at higher risk than African Americans 81 More men than women are diagnosed with leukemia and die from the disease Around 30 percent more men than women have leukemia 82 UK Edit Overall leukemia is the eleventh most common cancer in the UK around 8 600 people were diagnosed with the disease in 2011 and it is the ninth most common cause of cancer death around 4 800 people died in 2012 83 History Edit Rudolf Virchow Leukemia was first described by anatomist and surgeon Alfred Armand Louis Marie Velpeau in 1827 A more complete description was given by pathologist Rudolf Virchow in 1845 Around ten years after Virchow s findings pathologist Franz Ernst Christian Neumann found that the bone marrow of a deceased person with leukemia was colored dirty green yellow as opposed to the normal red This finding allowed Neumann to conclude that a bone marrow problem was responsible for the abnormal blood of people with leukemia 84 By 1900 leukemia was viewed as a family of diseases as opposed to a single disease By 1947 Boston pathologist Sidney Farber believed from past experiments that aminopterin a folic acid mimic could potentially cure leukemia in children The majority of the children with ALL who were tested showed signs of improvement in their bone marrow but none of them was actually cured This however led to further experiments 85 In 1962 researchers Emil J Freireich Jr and Emil Frei III used combination chemotherapy to attempt to cure leukemia The tests were successful with some people surviving long after the tests 86 Etymology Edit Observing an abnormally large number of white blood cells in a blood sample from a person Virchow called the condition Leukamie in German which he formed from the two Greek words leukos leykos meaning white and haima aἷma meaning blood 87 Society and culture EditAccording to Susan Sontag leukemia was often romanticized in 20th century fiction portrayed as a joy ending clean disease whose fair innocent and gentle victims die young or at the wrong time As such it was the cultural successor to tuberculosis which held this cultural position until it was discovered to be an infectious disease 88 The 1970 romance novel Love Story is an example of this romanticization of leukemia 89 In the United States around 5 4 billion is spent on treatment a year 90 Research directions EditSignificant research into the causes prevalence diagnosis treatment and prognosis of leukemia is being performed Hundreds of clinical trials are being planned or conducted at any given time 91 Studies may focus on effective means of treatment better ways of treating the disease improving the quality of life for people or appropriate care in remission or after cures citation needed In general there are two types of leukemia research clinical or translational research and basic research Clinical translational research focuses on studying the disease in a defined and generally immediately applicable way such as testing a new drug in people By contrast basic science research studies the disease process at a distance such as seeing whether a suspected carcinogen can cause leukemic changes in isolated cells in the laboratory or how the DNA changes inside leukemia cells as the disease progresses The results from basic research studies are generally less immediately useful to people with the disease 92 Treatment through gene therapy is currently being pursued One such approach used genetically modified T cells known as chimeric antigen receptor T cells CAR T cells to attack cancer cells In 2011 a year after treatment two of the three people with advanced chronic lymphocytic leukemia were reported to be cancer free 93 and in 2013 three of five subjects who had acute lymphocytic leukemia were reported to be in remission for five months to two years 94 Subsequent studies with a variety of CAR T types continue to be promising 95 As of 2018 two CAR T therapies have been approved by the Food and Drug Administration CAR T treatment has significant side effects 96 and loss of the antigen targeted by the CAR T cells is a common mechanism for relapse 95 The stem cells that cause different types of leukemia are also being researched 97 Pregnancy EditLeukemia is rarely associated with pregnancy affecting only about 1 in 10 000 pregnant women 98 How it is handled depends primarily on the type of leukemia Nearly all leukemias appearing in pregnant women are acute leukemias 99 Acute leukemias normally require prompt aggressive treatment despite significant risks of pregnancy loss and birth defects especially if chemotherapy is given during the developmentally sensitive first trimester 98 Chronic myelogenous leukemia can be treated with relative safety at any time during pregnancy with Interferon alpha hormones 98 Treatment for chronic lymphocytic leukemias which are rare in pregnant women can often be postponed until after the end of the pregnancy 98 99 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