Leukemia (American English) or leukaemia (British English) (from the Greek leukos - white, and haima - blood[1]) is a type

of cancer of the blood or bone marrow characterized by an abnormal increase of white blood cells. Leukemia is a broad term covering a spectrum of diseases. In turn, it is part of the even broader group of diseases affecting the blood, bone marrow and lymphoid system, which are all known as hematological neoplasms. In 2000, approximately 256,000 children and adults around the world developed some form of leukemia, and 209,000 died from it.[2] About 90% of all leukemias are diagnosed in adults.[3]

A Wright's stained bone marrow aspirate smear of patient with precursor B-cell acute lymphoblastic leukemia.

Classification
Cell type Lymphocytic leukemia (or "lymphoblastic") Myelogenous leukemia (also "myeloid" or "nonlymphocytic") Four major kinds of leukemia Acute Chronic Acute lymphoblastic Chronic lymphocytic leukemia leukemia (ALL) (CLL) Acute myelogenous leukemia Chronic myelogenous (AML) leukemia (CML) (or Myeloblastic)

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 numbers of immature blood cells. Crowding due to such cells makes the bone marrow unable to produce healthy blood cells. Immediate treatment is required in acute leukemia due to the rapid progression and accumulation of the malignant cells, which then spill over into the bloodstream and spread to other organs of the body. Acute forms of leukemia are the most common forms of leukemia in children. Chronic leukemia is characterized by the excessive build up of relatively mature, but still abnormal, white blood cells. Typically taking months or years to progress, the cells are produced at a much higher rate than normal cells, resulting in many abnormal white blood cells in the blood. Whereas acute leukemia must be treated immediately, chronic forms are sometimes monitored for some time before treatment to ensure maximum effectiveness of therapy. Chronic leukemia mostly occurs in older people, but can theoretically occur in any age group.

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

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

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

Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in young children. This disease also affects adults, especially those age 65 and older. Standard treatments involve chemotherapy and radiotherapy. The survival rates vary by age: 85% in children and 50% in adults.[4] Subtypes include precursor B acute lymphoblastic leukemia, precursor T acute lymphoblastic leukemia, Burkitt's leukemia, and acute biphenotypic leukemia. Chronic lymphocytic leukemia (CLL) most often affects adults over the age of 55. It sometimes occurs in younger adults, but it almost never affects children. Two-thirds of affected people are men. The five-year survival rate is 75%.[5] It is incurable, but there are many effective treatments. One subtype is B-cell prolymphocytic leukemia, a more aggressive disease. Acute myelogenous leukemia (AML) occurs more commonly in adults than in children, and more commonly in men than women. AML is treated with chemotherapy. The five-

year survival rate is 40%.[6] Subtypes of AML include acute promyelocytic leukemia, acute myeloblastic leukemia, and acute megakaryoblastic leukemia. Chronic myelogenous leukemia (CML) occurs mainly in adults. A very small number of children also develop this disease. Treatment is with imatinib (Gleevec in US, Glivec in Europe) [7] or other drugs. The five-year survival rate is 90%.[8][9] One subtype is chronic monocytic leukemia. Hairy cell leukemia (HCL) is sometimes considered a subset of CLL, but does not fit neatly into this pattern. About 80% of affected people are adult men. There are no reported cases in young children. HCL is incurable, but easily treatable. Survival is 96% to 100% at ten years.[10] 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.[11] Despite its overall rarity, it is also the most common type of mature T cell leukemia;[12] 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.[13] 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.

Signs and symptoms

Damage to the bone marrow, by way of displacing the normal bone marrow cells with higher numbers of immature white blood cells, results in a lack of blood platelets, which are important in the blood clotting process. This means people with leukemia may easily become bruised, bleed excessively, or develop pinprick bleeds (petechiae). White blood cells, which are involved in fighting pathogens, may be suppressed or dysfunctional. This could cause the patient's immune system to be unable to fight off a simple infection or to start attacking other body cells. Because leukemia prevents the immune system from working normally, some patients experience frequent infection, ranging from infected tonsils, sores in the mouth, or diarrhea to life-threatening pneumonia or opportunistic infections. Finally, the red blood cell deficiency leads to anemia, which may cause dyspnea and pallor. Some patients experience other symptoms, such as feeling sick, having fevers, chills, night sweats and other flu-like symptoms, or feeling fatigued. Some patients experience nausea or a

feeling of fullness due to an enlarged liver and spleen; this can result in unintentional weight loss. If the leukemic cells invade the central nervous system, then neurological symptoms (notably headaches) can occur. All symptoms associated with leukemia can be attributed to other diseases. Consequently, leukemia is always diagnosed through medical tests. The word leukemia, which means 'white blood', is derived from the disease's namesake high white blood cell counts that most leukemia patients have before treatment. The high number of white blood cells are apparent when a blood sample is viewed under a microscope. Frequently, these extra white blood cells are immature or dysfunctional. The excessive number of cells can also interfere with the level of other cells, causing a harmful imbalance in the blood count. Some leukemia patients do not have high white blood cell counts visible during a regular blood count. This less-common condition is called aleukemia. The bone marrow still contains cancerous white blood cells which disrupt the normal production of blood cells, but they remain in the marrow instead of entering the bloodstream, where they would be visible in a blood test. For an aleukemic patient, the white blood cell counts in the bloodstream can be normal or low. Aleukemia can occur in any of the four major types of leukemia, and is particularly common in hairy cell leukemia.[15]

Causes
No single known cause for all of the different types of leukemia exists. The known causes, which are not generally factors within the control of the average person, account for relatively few cases.[16] 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.[17] Among adults, the known causes are natural and artificial ionizing radiation, a few viruses such as Human T-lymphotropic virus, and some chemicals, notably benzene and alkylating chemotherapy agents for previous malignancies.[18][19][20] Use of tobacco is associated with a small increase in the risk of developing acute myeloid leukemia in adults.[18] Cohort and casecontrol studies have linked exposure to some petrochemicals and hair dyes to the development of some forms of leukemia. A few cases of maternal-fetal transmission have been reported.[18] Diet has very limited or no effect, although eating more vegetables may confer a small protective benefit.[16] Viruses have also been linked to some forms of leukemia. Experiments on mice and other mammals have demonstrated the relevance of retroviruses in leukemia, and human retroviruses have also been identified. The first human retrovirus identified was Human T-lymphotropic virus, or HTLV-1, is known to cause adult T-cell leukemia.[21] Some people have a genetic predisposition towards developing leukemia. This predisposition is demonstrated by family histories and twin studies.[18] The affected people may have a single

gene or multiple genes in common. In some cases, families tend to develop the same kind of leukemia as other members; in other families, affected people may develop different forms of leukemia or related blood cancers.[18] In addition to these genetic issues, people with chromosomal abnormalities or certain other genetic conditions have a greater risk of leukemia.[19] 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.[18] Whether non-ionizing radiation causes leukemia has been studied for several decades. The International Agency for Research on Cancer expert working group undertook a detailed review of all data on static and extremely low frequency electromagnetic energy, which occurs naturally and in association with the generation, transmission, and use of electrical power.[22] They concluded that there is limited evidence that high levels of ELF magnetic (but not electric) fields might cause childhood leukemia. Exposure to significant ELF magnetic fields might result in twofold excess risk for leukemia for children exposed to these high levels of magnetic fields.[22] However, the report also says that methodological weaknesses and biases in these studies have likely caused the risk to be overstated.[22] No evidence for a relationship to leukemia or another form of malignancy in adults has been demonstrated.[22] 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).[23]

Diagnosis
Diagnosis is usually based on repeated complete blood counts and a bone marrow examination following observations of the symptoms, however, in rare cases blood tests may not show if a patient has leukemia, usually this is because the leukemia is in the early stages or has entered remission. A lymph node biopsy can be performed as well in order 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 patient. When concerns arise about visible damage due to leukemia, doctors may use an X-ray, MRI, or ultrasound. These can potentially view leukemia's effects on such body parts as bones (X-ray), the brain (MRI), or the kidneys, spleen, and liver (ultrasound). Finally, CT scans are rarely used to check lymph nodes in the chest. Despite the use of these methods to diagnose whether or not a patient has leukemia, many people have not been diagnosed because many of the symptoms are vague, unspecific, and can refer to other diseases. For this reason, the American Cancer Society predicts that at least one-fifth of the people with leukemia have not yet been diagnosed.[15]

Mutation in SPRED1 gene has been associated with a predisposition to childhood leukemia.[24] SPRED1 gene mutations can be diagnosed with genetic sequencing.

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 useful. Promising treatment through gene therapy is currently being pursued.
[edit] Acute lymphoblastic Further information: Acute lymphoblastic leukemia#Treatment

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

Induction chemotherapy to bring about bone marrow remission. For adults, standard induction plans include prednisone, vincristine, and an anthracycline drug; other drug plans may include Lasparaginase or cyclophosphamide. For children with low-risk ALL, standard therapy usually consists of three drugs (prednisone, L-asparaginase, and vincristine) for the first month of treatment. Consolidation therapy or intensification therapy to eliminate any remaining leukemia cells. There are many different approaches to consolidation, but it is typically a high-dose, multi-drug treatment that is undertaken for a few months. Patients with low- to average-risk ALL receive therapy with antimetabolite drugs such as methotrexate and 6-mercaptopurine (6-MP). Highrisk patients receive higher drug doses of these drugs, plus additional drugs. CNS prophylaxis (preventive therapy) to stop the cancer from spreading to the brain and nervous system in high-risk patients. Standard prophylaxis may include radiation of the head and/or drugs delivered directly into the spine. Maintenance treatments with chemotherapeutic drugs to prevent disease recurrence once remission has been achieved. Maintenance therapy usually involves lower drug doses, and may continue for up to three years. Alternatively, allogeneic bone marrow transplantation may be appropriate for high-risk or relapsed patients.[25]

[edit] Chronic lymphocytic Decision to treat

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

Falling hemoglobin or platelet count Progression to a later stage of disease Painful, disease-related overgrowth of lymph nodes or spleen An increase in the rate of lymphocyte production [26]

[edit] Typical treatment approach

CLL is probably incurable by present treatments. The primary chemotherapeutic plan is combination chemotherapy with chlorambucil or cyclophosphamide, plus a corticosteroid such as prednisone or prednisolone. The use of a corticosteroid has the additional benefit of suppressing some related autoimmune diseases, such as immunohemolytic anemia or immunemediated thrombocytopenia. In resistant cases, single-agent treatments with nucleoside drugs such as fludarabine,[27] pentostatin, or cladribine may be successful. Younger patients may consider allogeneic or autologous bone marrow transplantation.[28]
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 patient and according to the specific subtype of AML. Overall, the strategy is to control bone marrow and systemic (whole-body) disease, while offering specific treatment for the central nervous system (CNS), if involved. In general, most oncologists rely on combinations of drugs for the initial, induction phase of chemotherapy. Such combination chemotherapy usually offers the benefits of early remission and a lower risk of disease resistance. Consolidation and maintenance treatments are intended to prevent disease recurrence. Consolidation treatment often entails a repetition of induction chemotherapy or the intensification chemotherapy with additional drugs. By contrast, maintenance treatment involves drug doses that are lower than those administered during the induction phase.[29]
[edit] Chronic myelogenous Further information: Chronic myelogenous leukemia#Treatment

There are many possible treatments for CML, but the standard of care for newly diagnosed patients is imatinib (Gleevec) therapy.[30] Compared to most anti-cancer drugs, it has relatively few side effects and can be taken orally at home. With this drug, more than 90% of patients will be able to keep the disease in check for at least five years,[30] so that CML becomes a chronic, manageable condition. In a more advanced, uncontrolled state, when the patient cannot tolerate imatinib, or if the patient wishes to attempt a permanent cure, then an allogeneic bone marrow transplantation may be performed. This procedure involves high-dose chemotherapy and radiation followed by infusion of bone marrow from a compatible donor. Approximately 30% of patients die from this procedure.[30]

[edit] Hairy cell Further information: Hairy cell leukemia#Treatment

Decision to treat Patients with hairy cell leukemia who are symptom-free typically do not receive immediate treatment. Treatment is generally considered necessary when the patient shows signs and symptoms such as low blood cell counts (e.g., infection-fighting neutrophil count below 1.0 K/L), frequent infections, unexplained bruises, anemia, or fatigue that is significant enough to disrupt the patient's everyday life. Typical treatment approach Patients who need treatment usually receive either one week of cladribine, given daily by intravenous infusion or a simple injection under the skin, or six months of pentostatin, given every four weeks by intravenous infusion. In most cases, one round of treatment will produce a prolonged remission.[31] Other treatments include rituximab infusion or self-injection with Interferon-alpha. In limited cases, the patient may benefit from splenectomy (removal of the spleen). These treatments are not typically given as the first treatment because their success rates are lower than cladribine or pentostatin.[32]
T-cell prolymphocytic Further information: T-cell prolymphocytic leukemia#Treatment

Most patients with T-cell prolymphocytic leukemia, a rare and aggressive leukemia with a median survival of less than one year, require immediate treatment.[33] T-cell prolymphocytic leukemia is difficult to treat, and it does not respond to most available chemotherapeutic drugs.[33] Many different treatments have been attempted, with limited success in certain patients: purine analogues (pentostatin, fludarabine, cladribine), chlorambucil, and various forms of combination chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone CHOP, cyclophosphamide, vincristine, prednisone [COP], vincristine, doxorubicin, prednisone, etoposide, cyclophosphamide, bleomycin VAPEC-B). Alemtuzumab (Campath), a monoclonal antibody that attacks white blood cells, has been used in treatment with greater success than previous options.[33] Some patients who successfully respond to treatment also undergo stem cell transplantation to consolidate the response.[33]
[edit] Juvenile myelomonocytic Further information: Juvenile myelomonocytic leukemia#Treatment

Treatment for juvenile myelomonocytic leukemia can include splenectomy, chemotherapy, and bone marrow transplantation.[34]

[edit] Other potential treatment being developed

A promising treatment being pursued by a team led by Dr. Carl June has recently been found through gene therapy, by turning T-cells into cancer-targeting attackers. As of August 2011, a year after treatment, two of the three patients are cancer-free while the third still has some cancer but is improved. [35]

History
Leukemia was first observed by pathologists Rudolf Virchow and John Hughes Bennett in 1845. Observing an abnormally large number of white blood cells in a blood sample from a patient, Virchow called the condition Leukmie in German, which he formed from the two Greek words leukos (), meaning "white", and aima (), meaning "blood". Around ten years after Virchow and Bennett's findings, pathologist Franz Ernst Christian Neumann found that one deceased leukemia patient's bone marrow 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 leukemia patients. By 1900 leukemia was viewed as a family of diseases as opposed to a single disease. By 1947 Boston pathologist Sydney 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 actually were cured. This, however, led 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 patients surviving long after the tests.[39]

Research
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.[40] Studies may focus on effective means of treatment, better ways of treating the disease, improving the quality of life for patients, or appropriate care in remission or after cures. In general, there are two types of leukemia research: clinical/translational research and basic science research. Clinical/translational research focuses on studying the disease in a defined and generally immediately patient-applicable way, whereas basic science research studies the disease process at a distance and the results from such studies are generally less immediately useful to patients with the disease.[41]

[edit] Society and culture

Leukemias are often romanticized in 20th century fiction. It is presented as a pure, clean disease (unlike, say, rectal cancer), whose innocent, beautiful, and spiritually sensitive victims tragically die young. As such, it is the successor to tuberculosis.[
http://en.wikipedia.org/wiki/Leukemia

Leukemia Overview

Cancer is a process of uncontrolled abnormal cell growth and development. Under normal circumstances, cells are formed, mature, carry out their intended function, and then die. New cells are constantly regenerated in the body to replace those cells and to maintain normal cellular function. Cancer represents the disturbance of this process, which can occur in several ways. Cells may grow and reproduce in a disorganized and out-of-control fashion. Cells may fail to develop properly, so they will not function normally. Cells may fail to die normally. One or a combination of these processes may occur when cells become cancerous. Leukemia is a cancer of blood-forming cells in the bone marrow. These deranged, immature cells accumulate in the blood and within organs of the body. They are not able to carry out the normal functions of blood cells. Normal blood contains 3 major groups of cells: white blood cells, red blood cells, and platelets. All 3 types of blood cells develop from one immature cell type, called blood/marrow stem cells, in a process called hematopoiesis.

These stem cells divide and develop to a more developed, but still immature precursor, called a blast, which then develops through several more stages, into a mature blood cell.

This process takes place in the bone marrow, which is the soft spongy material found in the center of most bones.

Each type of blood cells has its own different and essential function in the body.

White blood cells (leukocytes) are part of the immune system and help fight a variety of infections. They also help in the healing of wounds, cuts, and sores.

Red blood cells (erythrocytes) contain hemoglobin, which carries oxygen to, and removes carbon dioxide from, the cells throughout the various organs of the body.

Platelets, along with certain plasma proteins, help plug the holes in blood vessels and form clots once blood vessels are damaged or cut.

The first step in the process of stem cell maturation is differentiation into 2 groups: the myeloid stem cell line and the lymphoid stem cell line.

The myeloid stem cells, or lineage, develop into red blood cells, platelets, and certain types of white blood cells (granulocytes or monocytes).

The lymphoid stem cells, or lineage, develop into another type of white blood cell (lymphocytes).

Either lineage can be affected by leukemia. Leukemias that affect the myeloid lineage are called myelocytic (also myelogenous, myeloblastic, or nonlymphocytic) leukemias. Leukemias that affect the lymphoid lineage are called lymphocytic (also lymphoblastic or lymphogenous) leukemias.

Each of the 2 major types of leukemia, myelogenous and lymphocytic, include both acute and chronic forms.

Acute essentially refers to a disorder of rapid onset. In the acute myelocytic leukemias, the abnormal cells grow rapidly and do not mature. Most of these immature cells tend to die rapidly. In the acute lymphocytic leukemias, growth is not as rapid as that of the myelocytic cells. Rather, the cells tend to accumulate. Common to both types of leukemia is their inability to carry out the functions of healthy white blood cells. Untreated, death occurs within weeks or a few months.

In the chronic leukemias, the onset tends to be slow, and the cells generally mature abnormally and often accumulate in various organs, often over long intervals. Their ability to fight infections and assist in repairing injured tissues is impaired. However, unlike the acute forms of leukemia, untreated, these disorders may persist for many months or, as in the chronic lymphocytic group, many years. A distinctive feature of the chronic myelocytic type is its invariable conversion, if untreated, to a more rapidly fulminating acute type, leading to rapid death.

In summary, the 4 main types of leukemia are as follows:

Acute lymphocytic leukemia

Chronic lymphocytic leukemia

Acute myelocytic leukemia

Chronic myelocytic leukemia

Less common types include hairy cell leukemia and human T-cell leukemia. Leukemia affects people of all ages. Approximately 85% of leukemias in children are of the acute type.

Acute lymphocytic leukemia (ALL) affects both children and adults but is more common in children. It accounts for 65% of the acute leukemias in children.

Chronic lymphocytic leukemia (CLL) is essentially an adult disorder and is almost twice as common as chronic myelocytic leukemia.

Acute myelocytic leukemia (AML) is the most common acute leukemia in adults.

Chronic myelocytic leukemia (CML) is far more common in adults than in children.

As leukemic cells grow and eventually outnumber normal cells, the following events occur:

The normal blood cells are disabled, resulting in conditions such as frequent infections, bleeding problems (poor healing of small cuts or sores), and anemia (low red blood cell count).

The leukemia cells may collect in certain parts of the body, causing pain, swelling, and other problems.

Identifying the type of leukemia is important, since this determines which treatment is given.

Leukemia is newly diagnosed in about 29,000 adults and 2000 children each year in the United States.

In adults, the acute leukemias occur in those of all ages, whereas the chronic varieties, particularly CLL, tend to occur in people older than 40 years.

Leukemia is one of the most common cancers of children.

Leukemia is more common in people of European descent than in African Americans, Hispanic Americans, Asian Americans, or Native Americans.

Survival rates in leukemia have risen dramatically in the last 40 years with improvements in diagnosis and treatment.

In 1960, the overall 5-year survival rate for all leukemias was about 14%. It is now about 50%.

The highest survival rates occur in children with the so-called "common" ALL type.

Leukemia Causes

The exact cause of leukemia is unknown.

As with other cancers, smoking is considered a risk factor for leukemia, but many people who develop leukemia have never smoked, and many people who smoke never develop leukemia.

Long-term exposure to chemicals such as benzene or formaldehyde, typically in the workplace, is considered a risk factor for leukemia, but this accounts for relatively few cases of the disease.

Prolonged exposure to radiation is a risk factor, although this accounts for relatively few cases of leukemia. Doses of radiation used for diagnostic imaging such as x-rays and CT scans are nowhere near as prolonged or high as the doses needed to cause leukemia.

Other risk factors for leukemia include the following:

Previous chemotherapy: Chemotherapy, particularly certain of the alkylating agents and topoisomerase inhibitors, used to treat certain types of cancers, are linked to development of

leukemia later. It is likely that radiation treatment adds to the risk of leukemia associated with certain chemotherapy drugs.

Human T-cell leukemia virus 1 (HTLV-1): Infection with this virus is linked to human T-cell leukemia.

Myelodysplastic syndromes: In this unusual group of blood disorders, the net outcome is invariably an acute myelocytic process.

Down syndrome and other genetic diseases: Some diseases caused by abnormal chromosomes may increase risk for leukemia.

Family history: Having a first-degree relative (parent, brother, sister, or child) who has chronic lymphocytic leukemia increases ones risk of having the disease by as much as 4 times that of someone who does not have an affected relative.

Leukemia Symptoms

Symptoms usually develop fairly quickly in acute leukemias. Most cases of acute leukemia are diagnosed when the person visits his or her healthcare provider after becoming ill. Symptoms develop gradually in chronic leukemias and are generally not as severe as in acute leukemias. About 20% of people with chronic leukemia do not have symptoms at the time their disease is diagnosed. Some symptoms of leukemia are due to deficiencies of normal blood cells. Others are due to collections of leukemia cells in tissues and organs. Leukemia cells can collect in many different parts of the body, such as the testicles, brain, lymph nodes, liver, spleen, digestive tract, kidneys, lungs, eyes, and skin in effect, virtually every tissue site. The following symptoms of leukemia are common to all types:

Unexplained fevers

Frequent infections

Night sweats

Fatigue (feeling tired or washed out)

Weight loss

Easy bleeding or bruising

Collection of leukemia cells in certain parts of the body may cause the following symptoms:

Headache

Confusion

Balance problems

Blurred vision

Painful swellings in the neck, under the arms, or in the groin

Shortness of breath

Nausea or vomiting

Abdominal pain and/or swelling

Testicular pain and/or swelling

Pain in the bones or joints

Weakness or loss of muscle control

Seizures

It is important to emphasize that the symptoms of leukemia are nonspecific. This means that they are not unique to leukemia but are common to a number of diseases and conditions. Only a medical professional is able to distinguish leukemia from the other conditions that cause similar symptoms. http://www.emedicinehealth.com/leukemia/page3_em.htm When to Seek Medical Care

See a health care provider promptly if any of the following symptoms appear:

Unexplained fevers

Night sweats

Unexplained weight loss

Bleeding or bruising easily

Swelling in your neck, under your arm, or in your groin

Persistent pain in your abdomen, back, or bony areas

Persistent headache, confusion, balance problems, or difficulty concentrating

Sores or minor infections that fail to heal

Persistent blurred vision

Exams and Tests

Because the symptoms of leukemia are nonspecific and the causes are not clearly defined, one's health care provider will carry out extensive interviews and any appropriate tests in order to identify the underlying cause.

The health care provider will ask many questions about symptoms, current medical situations, medications, medical and surgical history, family history, work history, and habits and life style.

The physical examination includes a thorough evaluation of all symptoms, not merely lymph nodes and/or possible enlargements of the liver and spleen.

Blood tests: Blood is drawn from a vein in order to check the blood cell counts. In most cases of leukemia, the white blood cell count is very high (although it is not uncommon for the white cell count to be normal in many of the childhood acute lymphocytic leukemias) and the platelet and red cell counts are low. This makes the health care provider consider leukemia as the diagnosis. Other tests are performed to check liver and kidney functions and the possible presence of leukemic cells in the spinal fluid.

Biopsy: Because other conditions may give rise to atypical white cell counts, the only way to confirm the diagnosis of leukemia is via an aspirate and biopsy of the bone marrow.

Biopsy means to take a small sample of the relevant tissue to check for abnormal cells. In leukemia, a biopsy of the bone marrow must be taken and examined.

This procedure is usually performed in the medical office, usually by a specialist trained in the treatment of blood disorders, that is, a hematologist or a hematologist-oncologist. The procedure is brief (less than a few minutes) and preceded by a local injection for relief of pain.

Samples of both liquid (aspirate) and solid bone marrow (biopsy) are taken, usually from a hip bone.

The bone marrow is examined under a microscope, where the presence of leukemic cells confirms the suspected diagnosis.

Genetic studies: The chromosomes of the abnormal cells are examined to look for irregularities. This helps in classifying the various types of leukemia.

Lumbar puncture (spinal tap): Because the collection of leukemia cells in the central nervous system can affect mental processes, it is extremely important to know whether the fluid surrounding the brain and spinal cord (cerebrospinal fluid) is affected.

This procedure is referred to as a lumbar puncture or spinal tap and is usually carried out by the blood specialist in the office. After the procedure, the person needs to lie flat for 1-2 hours.

A small amount of the fluid is removed from the area around the spinal cord by inserting a hollow needle in the back at around the waist level. The needle is inserted in between the bones in the spine following a small injection into the skin over the injection site in order to minimize discomfort.

The fluid is examined for the presence of leukemia cells.

Lymph node excision: If the lymph nodes are enlarged, a node may require a biopsy if the bone marrow is difficult to interpret for some obscure reason. This is exceedingly uncommon.

Chest x-ray: A chest x-ray film is frequently taken to look for signs of infection or lymph node involvement by leukemia. Staging Staging is the way cancers are classified. Staging indicates the size or extent of the cancer, the degree to which other parts of the body are affected, and other important details. In general, leukemias are classified rather than staged in order to determine the most appropriate therapy.

All leukemias are classified according to their genotypes, or their unique chromosomal arrangements, which also enables the physicians to determine risk factors. In addiction, chronic myelogenous leukemia is classified by phase. The 3 phases are chronic phase, accelerated phase, and blast phase (or "blast crisis") and are defined by the number of blasts (leukemia cells) in the blood and bone marrow. Chronic lymphocytic leukemia is classified by 2 different staging systems, both based on the parts of the body affected by the leukemia.
Leukemia Treatment

Specialists who treat blood disorders and other kinds of cancer are either hematologists or hematologist-oncologists. These specialists treat leukemia.

Children are usually treated by a specialist in childhood cancers (pediatric hematologist or hematologist-oncologist).

These specialists are usually identified by the primary care physician, or less often, by a friend or relative.

On other occasions, more than one opinion may be sought by the patient or by the referring primary care physician whenever there is doubt or uncertainty, or whenever personalities are at odds.

Leukemia patients often find it helpful to take a family member or close friend along to these consultations in order to take notes and assist in remembering some of the points of the discussion. For children with leukemia, such is always the case.

Most patients are treated in major medical centers with state-of-the-art cancer treatment programs.

Once the patient has had the first encounter with the specialist, he or she will have ample opportunity to ask questions and discuss treatment options. The advantages and disadvantages of various treatment options are thoroughly discussed.

Leukemia treatment depends almost exclusively on the type. Modifying factors may be age, overall health, and prior therapy. Treatment is almost always carried out as part of carefully

controlled multi-center programs so that information from many different areas may be constantly analyzed and altered if the results appear to necessitate changes. The patient is always kept abreast of ongoing treatment activities and changes in the treatment plan.

Treatment commences only if the patient or the patient's guardian concurs.

In addition to the blood specialist, the patient's medical care team usually includes a specialist nurse or physician assistant, social worker (and for children, child-life worker), and sometimes a member of the clergy, all of whom play major roles in furthering well being.

Medical Treatment

Leukemia treatment falls into 2 categories: treatment to fight the cancer and treatment to relieve the symptoms of the disease and the side effects of the treatment (supportive care). The most widely used anti-leukemic treatment is chemotherapy, that is, the use of powerful drugs to kill leukemia cells.

Treatment usually involves combinations of chemotherapy.

Depending on the medication, therapy may be administered by vein or by mouth.

In some cases, chemotherapy can be given at the doctor's office or some may be taken at home; in other cases, the patient may have to stay in a hospital. This depends on which agents the patient is receiving along with his or her overall condition (sometimes measured in terms of "performance status").

Many people with leukemia have a semi-permanent intravenous (IV) line placed in the upper chest, near the shoulder.

A thin, plastic tube called a catheter is passed through the skin of the chest and inserted into a large vein. It is held in place, usually for the planned duration or therapy, with a few stitches, which makes it possible to use the same vein on numerous occasions without worry about the intravenous line being pulled out. The line is often burrowed under the skin.

People who have leukemia in their cerebrospinal fluid, or who are at high risk of having leukemic cells migrate to the spinal fluid, receive chemotherapy directly into the cerebrospinal canal. This is known as intrathecal chemotherapy.

Intrathecal chemotherapy is necessary because drugs given via IV do not sufficiently penetrate into the cerebrospinal fluid or brain and, thus, cannot kill leukemia cells there. Insufficient penetration of drugs into the cerebrospinal fluid results in uncontrolled growth of leukemic cells in the cerebrospinal fluid. Sometimes the therapy is inserted into a sac placed in one of the larger fluid-filled areas of the brain, a ventricle. The sac is known as an Ommaya reservoir, so named after its developer.

The reservoir stays in place for the duration of the treatment.

Chemotherapy kills cells or stops them from reproducing. Chemotherapy also kills rapidly growing healthy cells, accounting for many of the side effects of therapy.

The exact side effects depend on the particular agent or agents administered to the patient, and the severity of side effects depends on the doses given and the patient's tolerance.

Chemotherapy has its most severe effects on the bone marrow, the hair follicles, and the digestive system (from the mouth to the anus). These are the areas of the body where cells reproduce and replace themselves most quickly. Occasionally, the fingernails and toenails may splinter, crack, develop deep ridges, or stop growing.

Common side effects of chemotherapy include nausea and vomiting, diarrhea, hair loss, and irritation of the esophagus (the tube through which food passes from the mouth to the stomach).

Because chemotherapy kills normal blood cells, it can have some of the same effects as the leukemia itself: infections, anemia, and bleeding problems. Therefore, treatment of a patient with leukemia may involve the use of antibiotics and other anti-infective agents, red blood cell and platelet transfusions, and periodic injections to help increase the production of healthy red blood cells.

Newer agents are being developed that target leukemia cells and only minimally affecting healthy cells.

These agents greatly reduce the severity of side effects.

Imatinib (Gleevec), an agent used in the treatment of CML, is an example of such a chemotherapeutic drug.

Chemotherapy is usually given in cycles.

Each cycle consists of intensive treatment over several days followed by a few weeks without treatment for rest and recovery from side effects caused by the chemotherapy, particularly anemia and low white blood cells. The sequence is then repeated.

Chemotherapy regimens may be administered for 2-6 cycles, depending on subtype of leukemia and risk factors involved.

In accordance with particular treatment regimens, bone marrow exams may be carried out prior to each cycle of chemotherapy. After completion of treatment, the patient is evaluated again to see the effect of the chemotherapy on the leukemia.

Hematologists and oncologists often refer to phases of chemotherapy. Only in certain types of leukemia are all 3 phases used.

Induction: The purpose of this first phase is to kill as many leukemia cells as possible and bring about a remission.

Consolidation: In this phase, the goal is to seek out and kill the residual leukemia cells not killed by induction. Often, these cells are not detectable, but they are assumed to be still present.

Maintenance: The third phase is used to keep numbers of leukemia cells low, that is, to keep the disease in remission. The doses of chemotherapy are not as high as in the first 2 phases. This phase can last as long as 2 years.

The fundamental goal of chemotherapy is to cure the patient. Cure means that blood tests and bone marrow biopsy show no evidence of leukemia and the leukemia does not come back (relapse) over time. Only time can determine whether a remission (with no evidence of disease) will lead to disease-free survival (cure). In effect, remission may be short-lived, thereby requiring administration of new, previously unseen therapy. Results of this approach, often referred to as second-line therapy, are rarely curative. Stem cell transplant, if available, has the best chance of a second-line therapy cure.

Biological drug therapy: This type of therapy uses biological drugs that act similarly to the body's natural immune system, such as monoclonal antibodies, interferon, or interleukins.

Biological therapy consists of proteins like those produced naturally by the body's immune system to promote the body's innate ability to fight cancer.

Some people with chronic lymphocytic leukemia or acute myelogenous leukemia receive a monoclonal antibody. This is an antibody specifically designed to fight their type of leukemia cells.

Some people with chronic myelogenous leukemia receive injections of interferon, a protein produced by some of the body's lymphocytes, which on occasion may slow the growth of leukemia cells but which has many unpleasant side effects.

Radiation therapy: Radiotherapy is another treatment occasionally used in some types of leukemia.

A high-energy beam is targeted at an organ, such as the brain, bones, or spleen, where large numbers of leukemia cells have collected. The radiation kills these cells.

Radiation to the brain can have negative long-term effects on some people, especially children. It has been linked to learning or thinking problems later in life. For this reason, radiation to the brain is carefully calibrated and used only when absolutely required.

Stem cell transplantation: This is a treatment that allows use of very high doses of chemotherapy along with total body irradiation in order to kill the leukemic cells.

At the completion of high-dose (lethal) therapy, the patient's immune system is essentially depleted, and the patient is at high risk of developing serious life-threatening infections. Accordingly, these patients are treated in specially designed, sterile, air-filtered marrow transplant rooms.

Immediately upon completion of the high-dose therapy, stem cells from a healthy, complete blood cell matched donor, usually a sibling or less commonly a parent, are transplanted into a vein whereupon they migrate to the marrow where they grow and multiply before entering the circulation, a process that may take 2-3 weeks to be completed. On rare occasions, when a donor is not available, one's own marrow cells, usually pretreated in order to remove residual, but otherwise unseen, leukemic cells, are infused. This approach is far less successful than the use of matched donor cells.

If a patient receives stem cells from a matched donor, the type of stem cell transplant is called allogeneic. If the patients own stem cells are reintroduced back into the patient following high dose therapy, the infusion is called autologous. Marrow or stem cells from an identical twin is referred to as syngeneic.

Medications

Numerous chemotherapy and biological drug combinations may be prescribed by an oncologist. Which type and combination of therapy depends on many factors including the type and stage of leukemia, whether treating adult or childhood leukemia, ability to tolerate chemotherapy side effects, and if any previous treatment for the leukemia has occurred. Oncologists often work together regionally to decide which combination of chemotherapy and biological drugs are currently working best for their patients. Because of this, the drug combinations often vary and are able to change rapidly when improved results occur.
Surgery

Surgery is generally not used to treat leukemia. Occasionally, a person with leukemia that has spread to the spleen has the spleen removed. This is usually done only if the spleen is so large that it is causing problems for nearby organs.
Other Therapy

While alternative therapies, such as supplements, herbs, and body therapies, are not recommended as a replacement for medical treatment in leukemia, they may be considered complementary therapies. The following therapies have proponents but no scientific evidence of unequivocal benefit:

Acupuncture

Coenzyme Q10

Polysaccharide K

Alternative or complementary therapies should be discussed with the treating specialist. These therapies are not offered in conjunction with chemotherapy for leukemia because of the lack of definitive data.

Next Steps Follow-up

After completion of treatment, the diagnostic studies are repeated to see how the treatment has affected the leukemia. Many people have a reduction or even a disappearance of leukemia cells in their blood and bone marrow. This is called remission.

If the patient is in remission, his or her medical team watches the patient carefully over time for signs that the leukemia is coming back. In certain very high risk patients, who are likely to relapse despite a seeming remission, stem cell transplantation may follow induction therapy.

If the initial treatment does not cause remission, the doctor discusses alternate treatment plans, perhaps with new agents undergoing testing.

Another factor to be addressed may be impaired organ function secondary to therapy. Careful follow-up on any patient who has received extensive therapy, such as stem cell transplantation, should receive careful systemic evaluations in order to initiate corrective measures should any organ impairment be detected.
Prevention

No known way exists to prevent leukemia. Avoiding risk factors such as smoking, exposure to toxic chemicals, and exposure to radiation may help prevent some cases of leukemia.
http://www.emedicinehealth.com/leukemia/page12_em.htm#Prevention Outlook

The leukemias vary in their response to treatment.

Some types of acute leukemia respond very well to treatment and can be cured. Others do not have such a positive outlook.

Chronic leukemias usually cannot be cured, but they can be controlled for long periods. Some people with chronic leukemias respond well at first, but, over time, their remissions last for shorter and shorter intervals.

Specific factors are associated with outcomes in each type of leukemia. General factors associated with outcomes include the following:

Age

Percentages of leukemia cells in the blood and bone marrow

Degree to which specific systems of the body are affected by leukemia

Chromosome abnormalities in leukemia cells

Like other cancers, leukemia outlook is measured in terms of survival rates. The number of people who are still alive 5 years after treatment varies by type of leukemia. After 5 years, greater than 80% of patients without detectable disease will likely maintain a lifelong remission. Patients in remission longer than 15 years are considered unequivocal cures. One problem that requires concerted efforts by advocate groups is the need to address the reluctance on the part of the health care industry to offer health insurance for former pediatric leukemia patients whose disease-free survivals are considered "cures" by all available evidence.

Pathophysiology
In general, cancer is caused by damage to DNA that leads to uncontrolled cellular growth and spread throughout the body, either by increasing chemical signals that cause growth, or interrupting chemical signals that control growth. Damage can be caused through the formation of fusion genes, as well as the dysregulation of a proto-oncogene via juxtaposition of it to the promoter of another gene, e.g. the T-cell receptor gene. This damage may be caused by environmental factors such as chemicals, drugs or radiation. ALL is associated with exposure to radiation and chemicals in animals and humans. The association of radiation and leukemia in humans has been clearly established in studies of victims of the Chernobyl nuclear reactor and atom bombs in Hiroshima and Nagasaki. In animals, exposure to benzene and other chemicals can cause leukemia. Epidemiological studies have associated leukemia with workplace exposure to chemicals, but these studies are not as conclusive. Some evidence suggests that secondary leukemia can develop in individuals who are treated for other cancers with radiation and chemotherapy as a result of that treatment.[5]
http://nursingcrib.com/case-study/leukemia-case-study/

Leukemias are cancers of the blood-forming tissues. White blood cells may be produced in excessive amounts and are unable to work properly which weakens the immune system.

The blood is made up of fluid called plasma and three types of cells and each type has special functions. White blood cells (also called WBCs or leukocytes) help the body fight infections and other diseases. Red blood cells (also called RBCs or erythrocytes) carry oxygen from the lungs to the bodys tissues and take carbon dioxide from the tissues back to the lungs. The red blood cells give blood its color. Platelets (also called thrombocytes) help form blood clots that control bleeding. Blood cells are formed in the bone marrow, the soft, spongy center of bones. New (immature) blood cells are called blasts. Some blasts stay in the marrow to mature. Some travel to other parts of the body to mature. Normally, blood cells are produced in an orderly, controlled way, as the body needs them. This process helps keep us healthy. When leukemia develops, the body produces large numbers of abnormal blood cells. In most types of leukemia, the abnormal cells are white blood cells. The leukemia cells usually look different from normal blood cells, and they do not function properly. In both men and women, leukemia incidence is highest among whites and lowest among Chinese, Japanese, and Koreans. The incidence in men is about 50% higher than in women for all racial/ethnic groups except Vietnamese, among whom the male rates are only slightly higher. Ethnic differences in the incidence rates are small in the youngest adult age group (30-54 years), but become more evident in each of the older age groups. It is found that childhood leukemia rates are highest among Filipinos, followed by white Hispanics, non-Hispanic whites and blacks.