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Thursday, October 26, 2023

Alcoholic beverage

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Alcoholic_beverage
A selection of alcoholic drinks: red wine, malt whisky, lager, sparkling wine, lager, cherry liqueur and red wine
A liquor store in the United States. Global sales of alcoholic drinks exceeded $1 trillion in 2018.

An alcoholic beverage (also called an adult beverage, alcoholic drink, strong drink, or simply a drink) is a drink that contains ethanol, a type of alcohol that acts as a drug and is produced by fermentation of grains, fruits, or other sources of sugar. The consumption of alcoholic drinks, often referred to as "drinking", plays an important social role in many cultures. Most countries have laws regulating the production, sale, and consumption of alcoholic beverages, and the temperance movement advocates against the consumption of alcoholic beverages. Regulations may require the labeling of the percentage alcohol content (as ABV or proof) and the use of a warning label. Some countries ban such activities entirely, but alcoholic drinks are legal in most parts of the world. The global alcoholic drink industry exceeded $1 trillion in 2018.

Alcohol is a depressant, which in low doses causes euphoria, reduces anxiety, and increases sociability. In higher doses, it causes drunkenness, stupor, unconsciousness, or death. Long-term use can lead to an alcohol use disorder, an increased risk of developing several types of cancer, cardiovascular disease, and physical dependence.

According to the World Health Organization, alcohol is the highest risk-group carcinogen, and no quantity of its consumption can be considered safe. According to the Centers for Disease Control and Prevention dietary guidelines on alcohol, it is not recommended to start consuming alcohol for any reason; for those who drink, "drinking less is better for health than drinking more", and growing research indicates that even moderate drinking has no positive health benefits overall. A systemic metanalysis of 107 cohort studies concluded low daily alcohol intake gives neither harm nor benefit; however, increased consumption, even at relatively low levels of daily intake (>2 beverages for women and >3 beverages for men), does increase health and mortality risks.

Alcohol is one of the most widely used recreational drugs in the world, and about 33% of all humans currently drink alcohol. In 2015, among Americans, 86% of adults had consumed alcohol at some point, with 70% drinking it in the last year and 56% in the last month. Alcoholic drinks are typically divided into three classes—beers, wines, and spirits—and typically their alcohol content is between 3% and 50%.

Discovery of late Stone Age jugs suggest that intentionally fermented drinks existed at least as early as the Neolithic period (c. 10,000 BC). Several other animals are affected by alcohol similarly to humans and, once they consume it, will consume it again if given the opportunity, though humans are the only species known to produce alcoholic drinks intentionally.

Fermented drinks

Wine (left) and beer (right) are served in different glasses.

Beer

Beer is a beverage fermented from grain mash. It is typically made from barley or a blend of several grains and flavored with hops. Most beer is naturally carbonated as part of the fermentation process. If the fermented mash is distilled, then the drink becomes a spirit. Beer is the most consumed alcoholic beverage in the world.

Cider

Cider or cyder (/ˈsdər/ SY-dər) is a fermented alcoholic drink made from any fruit juice; apple juice (traditional and most common), peaches, pears ("Perry" cider) or other fruit. Cider alcohol content varies from 1.2% ABV to 8.5% or more in traditional English ciders. In some regions, cider may be called "apple wine".

Fermented tea

Fermented tea (also known as post-fermented tea or dark tea) is a class of tea that has undergone microbial fermentation, from several months to many years. The tea leaves and the liquor made from them become darker with oxidation. Thus, the various kinds of fermented teas produced across China are also referred to as dark tea, not be confused with black tea. The most famous fermented tea is kombucha which is often homebrewed, pu-erh, produced in Yunnan Province, and the Anhua dark tea produced in Anhua County of Hunan Province. The majority of kombucha on the market are under 0.5% ABV.

Fermented water

Fermented water is an ethanol-based water solution with approximately 15-17% ABV without sweet reserve. Fermented water is exclusively fermented with white sugar, yeast, and water. Fermented water is clarified after the fermentation to produce a colorless or off-white liquid with no discernible taste other than that of ethanol.

Fermented sugar water

Fermented sugar water is fermented water with added refined sugar.

Mead

Mead (/md/) is an alcoholic drink made by fermenting honey with water, sometimes with various fruits, spices, grains, or hops. The alcoholic content of mead may range from as low as 3% ABV to more than 20%. The defining characteristic of mead is that the majority of the drink's fermentable sugar is derived from honey. Mead can also be referred to as "honeywine."

Pulque

Pulque is the Mesoamerican fermented drink made from the "honey water" of maguey, Agave americana. Pulque can be distilled to produce tequila or mescal Mezcal.

Rice wine

Sake, huangjiu, mijiu, and cheongju are popular examples of East Asian rice wine.

Wine

Wine is a fermented beverage most commonly produced from grapes. Wine involves a longer fermentation process than beer and often a long aging process (months or years), resulting in an alcohol content of 9%–16% ABV.

Sparkling wines such French Champagne, Catalan Cava or Italian Prosecco are also made from grapes, with a secondary fermentation.

Fruit wines are made from fruits other than grapes, such as plums, cherries, or apples.

Distilled beverages

Distilled beverages (also called liquors or spirit drinks) are alcoholic drinks produced by distilling (i.e., concentrating by distillation) ethanol produced by means of fermenting grain, fruit, or vegetables. Unsweetened, distilled, alcoholic drinks that have an alcohol content of at least 20% ABV are called spirits. For the most common distilled drinks, such as whiskey and vodka, the alcohol content is around 40%. The term hard liquor is used in North America to distinguish distilled drinks from undistilled ones (implicitly weaker). Vodka, gin, baijiu, shōchū, soju, tequila, whiskey, brandy and rum are examples of distilled drinks. Distilling concentrates the alcohol and eliminates some of the congeners. Freeze distillation concentrates ethanol along with methanol and fusel alcohols (fermentation by-products partially removed by distillation) in applejack.

Fortified wine is wine, such as port or sherry, to which a distilled beverage (usually brandy) has been added. Fortified wine is distinguished from spirits made from wine in that spirits are produced by means of distillation, while fortified wine is wine that has had a spirit added to it. Many different styles of fortified wine have been developed, including port, sherry, madeira, marsala, commandaria, and the aromatized wine vermouth.

Rectified spirit

Rectified spirit, also called "neutral grain spirit", is alcohol which has been purified by means of "rectification" (i.e. repeated distillation). The term neutral refers to the spirit's lack of flavor that would have been present if the mash ingredients had been distilled to a lower level of alcoholic purity. Rectified spirit also lacks any flavoring added to it after distillation (as is done, for example, with gin). Other kinds of spirits, such as whiskey, are distilled to a lower alcohol percentage to preserve the flavor of the mash.

Rectified spirit is a clear, colorless, flammable liquid that may contain as much as 95% ABV. It is often used for medicinal purposes. It may be a grain spirit or it may be made from other plants. It is used in mixed drinks, liqueurs, and tinctures, and also as a household solvent.

Congeners

In the alcoholic drinks industry, congeners are substances produced during fermentation. These substances include small amounts of chemicals such as occasionally desired other alcohols, like propanol and 3-methyl-1-butanol, but also compounds that are never desired such as acetone, acetaldehyde and glycols. Congeners are responsible for most of the taste and aroma of distilled alcoholic drinks, and contribute to the taste of non-distilled drinks. It has been suggested that these substances contribute to the symptoms of a hangover. Tannins are congeners found in wine in the presence of phenolic compounds. Wine tannins add bitterness, have a drying sensation, taste herbaceous, and are often described as astringent. Wine tannins adds balance, complexity, structure and makes a wine last longer, so they play an important role in the aging of wine.

Amount of use

Alcohol consumption per person in 2016. Consumption of alcohol is measured in liters of pure alcohol per person aged 15 or older.

The average number of people who drink as of 2016 was 39% for males and 25% for females (2.4 billion people in total). Females on average drink 0.7 drinks per day while males drink 1.7 drinks per day. The rates of drinking varies significantly in different areas of the world.

Reasons for use

Apéritifs and digestifs

An apéritif is any alcoholic beverage usually served before a meal to stimulate the appetite, while a digestif is any alcoholic beverage served after a meal for the stated purpose of improving digestion. Fortified wine, liqueurs, and dry champagne are common apéritifs. Because apéritifs are served before dining, they are usually dry rather than sweet. One example is Cinzano, a brand of vermouth. Digestifs include brandy, fortified wines and herb-infused spirits (Drambuie).

Caloric content

The USDA uses a figure of 6.93 kilocalories (29.0 kJ) per gram of alcohol (5.47 kcal or 22.9 kJ per ml) for calculating food energy. For distilled spirits, a standard serving in the United States is 44 ml (1.5 US fl oz), which at 40% ethanol (80 proof), would be 14 grams and 98 calories. For other than distilled spirits, many alcoholic drinks contain carbohydrates, which adds to the calories per serving.

Alcoholic drinks are considered empty calorie foods because other than food energy they contribute no essential nutrients. According to the U.S. Department of Agriculture, based on NHANES 2013–2014 surveys, women in the US ages 20 and up consume on average 6.8 grams/day and men consume on average 15.5 grams/day.

Alcohol is known to potentiate the insulin response of the human body to glucose, which, in essence, "instructs" the body to convert consumed carbohydrates into fat and to suppress carbohydrate and fat oxidation. Ethanol is directly processed in the liver to acetyl CoA, the same intermediate product as in glucose metabolism. Because ethanol is mostly metabolized and consumed by the liver, chronic excessive use can lead to fatty liver. This leads to a chronic inflammation of the liver and eventually alcoholic liver disease.

Flavoring

Reduction of red wine for a sauce by cooking it on a stovetop. It is called a reduction because the heat boils off some of the water and most of the more volatile alcohol, leaving a more concentrated, wine-flavoured sauce.

Pure ethanol tastes bitter to humans; some people also describe it as sweet. However, ethanol is also a moderately good solvent for many fatty substances and essential oils. This facilitates the use of flavoring and coloring compounds in alcoholic drinks as a taste mask, especially in distilled drinks. Some flavors may be naturally present in the beverage's raw material. Beer and wine may also be flavored before fermentation, and spirits may be flavored before, during, or after distillation. Sometimes flavor is obtained by allowing the beverage to stand for months or years in oak barrels, usually made of American or French oak. A few brands of spirits may also have fruit or herbs inserted into the bottle at the time of bottling.

Wine is important in cuisine not just for its value as an accompanying beverage, but as a flavor agent, primarily in stocks and braising, since its acidity lends balance to rich savory or sweet dishes. Wine sauce is an example of a culinary sauce that uses wine as a primary ingredient. Natural wines may exhibit a broad range of alcohol content, from below 9% to above 16% ABV, with most wines being in the 12.5–14.5% range. Fortified wines (usually with brandy) may contain 20% alcohol or more.

Alcohol measurement

Alcohol concentration

Typical ABV ranges
Fruit juices < 0.1%
Cider, wine coolers 4%–8%
Beers typically 5% (range is from 3–15%)
Wines typically 13.5% (range is from 8%–17%)
Sakes 15–16%
Fortified wines 15–22%
Spirits typically 30%-40% (range is from 15% to, in some rare cases, up to 98%)

The concentration of alcohol in a beverage is usually stated as the percentage of alcohol by volume  (ABV, the number of milliliters (ml) of pure ethanol in 100 ml of beverage) or as proof. In the United States, proof is twice the percentage of alcohol by volume at 60 degrees Fahrenheit (e.g. 80 proof = 40% ABV). Degrees proof were formerly used in the United Kingdom, where 100 degrees proof was equivalent to 57.1% ABV. Historically, this was the most dilute spirit that would sustain the combustion of gunpowder.

Ordinary distillation cannot produce alcohol of more than 95.6% by weight, which is about 97.2% ABV (194.4 proof) because at that point alcohol is an azeotrope with water. A spirit which contains a very high level of alcohol and does not contain any added flavoring is commonly called a neutral spirit. Generally, any distilled alcoholic beverage of 170 US proof or higher is considered to be a neutral spirit.

Most yeasts cannot reproduce when the concentration of alcohol is higher than about 18%, so that is the practical limit for the strength of fermented drinks such as wine, beer, and sake. However, some strains of yeast have been developed that can reproduce in solutions of up to 25% ABV.

Serving measures

Shot sizes

Shot sizes vary significantly from country to country. In the United Kingdom, serving size in licensed premises is regulated under the Weights and Measures Act (1985). A single serving size of spirits (gin, whisky, rum, and vodka) are sold in 25 ml or 35 ml quantities or multiples thereof. Beer is typically served in pints (568 ml), but is also served in half-pints or third-pints. In Israel, a single serving size of spirits is about twice as much, 50 or 60 mL.

The shape of a glass can have a significant effect on how much one pours. A Cornell University study of students and bartenders' pouring showed both groups pour more into short, wide glasses than into tall, slender glasses. Aiming to pour one shot of alcohol (1.5 ounces or 44.3 ml), students on average poured 45.5 ml & 59.6 ml (30% more) respectively into the tall and short glasses. The bartenders scored similarly, on average pouring 20.5% more into the short glasses. More experienced bartenders were more accurate, pouring 10.3% less alcohol than less experienced bartenders. Practice reduced the tendency of both groups to over pour for tall, slender glasses but not for short, wide glasses. These misperceptions are attributed to two perceptual biases: (1) Estimating that tall, slender glasses have more volume than shorter, wider glasses; and (2) Over focusing on the height of the liquid and disregarding the width.

Standard drinks

A "standard drink" of hard liquor does not necessarily reflect a typical serving size, such as seen here.

There is no single standard, but a standard drink of 10g alcohol, which is used in the WHO AUDIT (Alcohol Use Disorders Identification Test)'s questionnaire form example, have been adopted by more countries than any other amount. 10 grams is equivalent to 12.7 millilitres.

A standard drink is a notional drink that contains a specified amount of pure alcohol. The standard drink is used in many countries to quantify alcohol intake. It is usually expressed as a measure of beer, wine, or spirits. One standard drink always contains the same amount of alcohol regardless of serving size or the type of alcoholic beverage. The standard drink varies significantly from country to country. For example, it is 7.62 ml (6 grams) of alcohol in Austria, but in Japan it is 25 ml (19.75 grams).

  • In the United Kingdom, there is a system of units of alcohol which serves as a guideline for alcohol consumption. A single unit of alcohol is defined as 10 ml. The number of units present in a typical drink is sometimes printed on bottles. The system is intended as an aid to people who are regulating the amount of alcohol they drink; it is not used to determine serving sizes.
  • In the United States, the standard drink contains 0.6 US fluid ounces (18 ml) of alcohol. This is approximately the amount of alcohol in a 12-US-fluid-ounce (350 ml) glass of beer, a 5-US-fluid-ounce (150 ml) glass of wine, or a 1.5-US-fluid-ounce (44 ml) glass of a 40% ABV (80 US proof) spirit.

Laws

Alcohol laws regulate the manufacture, packaging, labelling, distribution, sale, consumption, blood alcohol content of motor vehicle drivers, open containers, and transportation of alcoholic drinks. Such laws generally seek to reduce the adverse health and social impacts of alcohol consumption. In particular, alcohol laws set the legal drinking age, which usually varies between 15 and 21 years old, sometimes depending upon the type of alcoholic drink (e.g., beer vs wine vs hard liquor or distillates). Some countries do not have a legal drinking or purchasing age, but most countries set the minimum age at 18 years.

Some countries, such as the U.S., have the drinking age higher than the legal age of majority (18), at age 21 in all 50 states. Such laws may take the form of permitting distribution only to licensed stores, monopoly stores, or pubs and they are often combined with taxation, which serves to reduce the demand for alcohol (by raising its price) and it is a form of revenue for governments. These laws also often limit the hours or days (e.g., "blue laws") on which alcohol may be sold or served, as can also be seen in the "last call" ritual in US and Canadian bars, where bartenders and servers ask patrons to place their last orders for alcohol, due to serving hour cutoff laws. In some countries, alcohol cannot be sold to a person who is already intoxicated. Alcohol laws in many countries prohibit drunk driving.

In some jurisdictions, alcoholic drinks are totally prohibited for reasons of religion (e.g., Islamic countries with sharia law) or for reasons of local option, public health, and morals (e.g., Prohibition in the United States from 1920 to 1933). In jurisdictions which enforce sharia law, the consumption of alcoholic drinks is an illegal offense, although such laws may exempt non-Muslims.

Alcohol and health

An alcohol packaging warning applied to alcoholic beverages in the Yukon, Canada (see Northern Territories Alcohol Labels Study)

Light and moderate alcohol consumption increases cancer risk in individuals, especially with respect to squamous cell carcinoma of the esophagus, oropharyngeal cancer, and breast cancer.

Some nations have introduced alcohol packaging warning messages that inform consumers about alcohol and cancer, as well as foetal alcohol syndrome. The addition of warning labels on alcoholic beverages is historically supported by organizations of the temperance movement, such as the Woman's Christian Temperance Union, as well as by medical organisations, such as the Irish Cancer Society.

History

  • 10,000–5000 BC: Discovery of late Stone Age jugs suggests that intentionally fermented drinks existed at least as early as the Neolithic period.
  • 7000–5600 BC: Examination and analysis of ancient pottery jars from the neolithic village of Jiahu in the Henan province of northern China revealed residue left behind by the alcoholic drinks they had once contained. According to a study published in the Proceedings of the National Academy of Sciences, chemical analysis of the residue confirmed that a fermented drink made of grape and hawthorn fruit wine, honey mead and rice beer was being produced in 7000–5600 BC (McGovern et al., 2005; McGovern 2009). The results of this analysis were published in December 2004.
  • 9th–10th centuries AD: Medieval Muslim chemists such as Jābir ibn Ḥayyān (Latin: Geber, ninth century) and Abū Bakr al-Rāzī (Latin: Rhazes, c. 865–925) experimented extensively with the distillation of various substances. The distillation of wine is attested in Arabic works attributed to al-Kindī (c. 801–873 CE) and to al-Fārābī (c. 872–950), and in the 28th book of al-Zahrāwī's (Latin: Abulcasis, 936–1013) Kitāb al-Taṣrīf (later translated into Latin as Liber servatoris).
  • 12th century: The process of distillation spread from the Middle East to Italy, where distilled alcoholic drinks were recorded in the mid-12th century. In China, archaeological evidence indicates that the true distillation of alcohol began during the 12th century Jin or Southern Song dynasties. A still has been found at an archaeological site in Qinglong, Hebei, dating to the 12th century.
  • 14th century: In India, the true distillation of alcohol was introduced from the Middle East, and was in wide use in the Delhi Sultanate by the 14th century. By the early 14th century, distilled alcoholic drinks had spread throughout the European continent.

Leukemia

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Leukemia
 
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
Usual onsetAll ages, most common in 60s and 70s. It is the most common malignant cancer in children, but the cure rates are also higher for them.
CausesInherited and environmental factors
Risk factorsSmoking, family history, ionizing radiation, some chemicals such as trichloroethylene, prior chemotherapy, Down syndrome.
Diagnostic methodBlood tests, bone marrow biopsy
TreatmentChemotherapy, radiation therapy, targeted therapy, bone marrow transplant, supportive care
PrognosisFive-year survival rate 57% (U.S.)
Frequency2.3 million (2015)
Deaths353,500 (2015)

Leukemia (also spelled leukaemia and pronounced /lˈkmə/ 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. These blood cells are not fully developed and are called blasts or leukemia cells. Symptoms may include bleeding and bruising, bone pain, fatigue, fever, and an increased risk of infections. These symptoms occur due to a lack of normal blood cells. Diagnosis is typically made by blood tests or bone marrow biopsy.

The exact cause of leukemia is unknown. A combination of genetic factors and environmental (non-inherited) factors are believed to play a role. Risk factors include smoking, ionizing radiation, petrochemicals (such as benzene), prior chemotherapy, and Down syndrome. People with a family history of leukemia are also at higher risk. 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. 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.

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. Certain types of leukemia may be managed with watchful waiting. The success of treatment depends on the type of leukemia and the age of the person. Outcomes have improved in the developed world. Five-year survival rate is 65% in the United States. 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. In children with acute leukemia who are cancer-free after five years, the cancer is unlikely to return.

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

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)

General classification

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

  • 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 (or, more rarely, red 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:

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.

Specific types

Pre-leukemia

Signs and symptoms

Common symptoms of chronic or acute leukemia

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

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 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.

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

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.

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.

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.

Causes

Studies in 2009 and 2010 have shown a positive correlation between exposure to formaldehyde and the development of leukemia, particularly myeloid leukemia. The different leukemias likely have different causes.

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.

Among adults, the known causes are natural and artificial ionizing radiation and petrochemicals, notably benzene and alkylating chemotherapy agents for previous malignancies. Use of tobacco is associated with a small increase in the risk of developing acute myeloid leukemia in adults. 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.

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

A few cases of maternal-fetal transmission (a baby acquires leukemia because its mother had leukemia during the pregnancy) have been reported. 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.

In a recent systematic review and meta-analysis of any type of leukemia in neonates using phototherapy, typically to treat neonatal jaundice, a statistically significant association was detected between using phototherapy 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. 

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.

Genetic conditions

Some people have a genetic predisposition towards developing leukemia. This predisposition is demonstrated by family histories and twin studies. 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.

In addition to these genetic issues, people with chromosomal abnormalities or certain other genetic conditions have a greater risk of leukemia. 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. Mutation in SPRED1 gene has been associated with a predisposition to childhood leukemia.

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.

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. They concluded that there is limited evidence that high levels of ELF magnetic (but not electric) fields might cause some cases of childhood leukemia. No evidence for a relationship to leukemia or another form of malignancy in adults has been demonstrated. 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).

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.

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.

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.

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

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. 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.

Chronic lymphocytic

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:

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, 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.

Acute myelogenous

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.

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.

Chronic myelogenous

There are many possible treatments for CML, but the standard of care for newly diagnosed people is imatinib (Gleevec) therapy. 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, 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.

Hairy cell

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.

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.

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.

T-cell prolymphocytic

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

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

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

Juvenile myelomonocytic

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

Prognosis

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

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.

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. In 2000, approximately 256,000 children and adults around the world developed a form of leukemia, and 209,000 died from it. 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. 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. Leukemia occurs more commonly in the developed world.

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. Approximately 44,270 new cases of leukemia were diagnosed in the year 2008 in the US. 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.

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

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.

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

Australia

In Australia, leukemia is the eleventh most common cancer. In 2014–2018, Australians diagnosed with leukaemia had a 64% chance (65% for males and 64% for females) of surviving for five years compared to the rest of the Australian population–there was a 21% increase in survival rates between 1989–1993.

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).

History

Photo of the upper body of a bespectacled man
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.

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 were actually cured. Nevertheless, this result did lead to further experiments.

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.

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'. It was formerly also called leucemia.

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. The 1970 romance novel Love Story is an example of this romanticization of leukemia.

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

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. 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.

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.

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 and in 2013, three of five subjects who had acute lymphocytic leukemia were reported to be in remission for five months to two years. Subsequent studies with a variety of CAR-T types continue to be promising. As of 2018, two CAR-T therapies have been approved by the Food and Drug Administration. CAR-T treatment has significant side effects, and loss of the antigen targeted by the CAR-T cells is a common mechanism for relapse. The stem cells that cause different types of leukemia are also being researched.

Pregnancy

Leukemia is rarely associated with pregnancy, affecting only about 1 in 10,000 pregnant women. How it is handled depends primarily on the type of leukemia. Nearly all leukemias appearing in pregnant women are acute leukemias. 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. Chronic myelogenous leukemia can be treated with relative safety at any time during pregnancy with Interferon-alpha hormones. Treatment for chronic lymphocytic leukemias, which are rare in pregnant women, can often be postponed until after the end of the pregnancy.

Occam's razor

From Wikipedia, the free encyclopedia https://en.wikipedia.org/wiki/Occam%27s_razor In philosophy , Occa...