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What is leukemia?

Leukemia is cancer of the blood and bone marrow. It develops when bone marrow, which produces blood cells, forms abnormal white blood cells that divide out of control. Normal white blood cells are the body's infection fighters, but these abnormal white blood cells, called leukemia cells, don't die at the same rate as normal blood cells. Instead, they accumulate and crowd out normal cells, like red blood cells, platelets, and normal white blood cells and their precursors, in the bone marrow. This can lead to difficulty getting enough oxygen to tissues (anemia), excess bleeding, and repeated infections.

Over time, leukemia cells can spread through the bone marrow and bloodstream, where they continue to divide, sometimes forming tumors and damaging organs. The organs affected depend on the type of leukemia. For example, the spleen, liver, and lymph nodes may become enlarged and swollen with the abnormal cells. Sometimes, leukemia cells reach the central nervous system (the brain and spinal cord) and build up in the cerebrospinal fluid.

In the United States, more than 43,000 adults and 5,000 children are diagnosed each year with leukemia. While exposure to radiation, benzene, and some anticancer drugs have been shown to increase the risk of developing leukemia, and a few cases are associated with genetic disorders or rare viral infections, the cause of most leukemias is not known.

Accordion Title
About Leukemia
  • Types

    There are multiple types of leukemia, classified based on the type of white blood cell the cancer arose from and how fast it is progressing. Leukemia begins in the bone marrow, located in the soft center of the body's larger bones, which makes precursors of red blood cells, platelets, and white blood cells. These immature blood cell precursors grow and mature in the bone marrow until being released into the bloodstream.

    Two categories of immature precursor cells produce white blood cells: myeloid cells and lymphoid cells. Myeloid cells produce red blood cells, platelets, and several white blood cells types, known as granulocytes. Granulocytes circulate in the blood and fight infections by killing and digesting bacteria. Lymphoid cells develop into lymphocytes, another type of white blood cell that is found in both the blood and the lymphatic system. They coordinate the body's immune response and a subset of lymphocytes produce antibodies.

    (Other types of cancer affect lymphocytes but occur in the lymphatic system, not the bone marrow. These are called lymphomas and are diagnosed and treated differently. They are discussed in the Lymphoma article.)

    Leukemia is categorized based on whether the abnormal white blood cells are from lymphoid cells or myeloid cells. A further classification is based on if the cancer is fast developing and rapidly fatal if not treated (acute) or more slowly developing (chronic). That leads to four main categories of leukemia:

    • Acute lymphoblastic leukemia (ALL). ALL is the most common type of cancer in children from one to seven years of age and the most common leukemia in children from infancy to age 19, although it also affects adults. In young children, survival chances are especially good. In ALL, leukemic blast cells accumulate in the bone marrow and blood and the cancer progresses quickly without treatment. It can spread to the lymph nodes and central nervous system. Untreated ALL can lead to anemia, poor immunity, and easy bleeding and bruising.
    • Chronic lymphocytic leukemia (CLL). This is the most common leukemia of adults in Western countries and it almost never affects teens or children. It tends to be found in those over the age of 55 or 60 and the mean age at diagnosis is 65. This disease progresses more slowly compared with some other types of leukemia. The slow-growing CLL cells don't typically block the production of normal cells in the marrow as much as they do in ALL. That is why the early stages of CLL are often not as severe as early stages of ALL. The slow-growing form of CLL can remain stable for years and does not require treatment. However, there is a faster-growing form of CLL that blocks normal blood cell production and requires treatment. People with CLL may have enlarged lymph nodes, immunoglobulin deficiencies that lead to poor immunity, autoimmunity (such as autoimmune hemolysis), and an enlarged spleen.
    • Acute myeloid leukemia (AML). This is the most common acute leukemia in adults. Adults older than 50 are more likely than children to develop AML and adolescents over 15 are more likely to develop it than younger children. AML is generally a rapidly developing cancer where immature myeloid cells continually divide in the bone marrow or other tissue and can replace bone marrow with immature, dysfunctional white blood cells. Untreated AML leads to anemia, poor immunity, and very easy bruising and bleeding.
    • Chronic myelogenous (myeloid) leukemia (CML). CML usually occurs in adults, with people 65 and over at greater risk. It rarely affects children. People with CML often have no symptoms at first and are often diagnosed during a routine blood test or physical. When symptoms do appear, they are similar to common, less serious illness and include low energy, pale skin, stomach discomfort caused by an enlarged spleen, and unexplained weight loss. CML can be traced to abnormal chromosomes where, inside a stem cell in the bone marrow, pieces from two chromosomes break off and switch places (translocation). This results in an altered, fused gene (called BCR/ABL) on chromosome 22 (also known as the Philadelphia chromosome). This altered gene makes an abnormally functional protein that leads to the overproduction of white blood cells. Left untreated, CML leads to anemia, poor immunity, excessive bruising and bleeding, and markedly enlarged spleen.
  • Signs and Symptoms

    Leukemia-related symptoms vary depending on the kind of leukemia.

    Acute leukemia is often diagnosed because the affected person feels ill. The person may have symptoms related to not having enough normal blood cells, such as:

    • Weakness, shortness of breath, and pale skin due to a lack of red blood cells (anemia)
    • Bleeding and bruising due to a lack of platelets (thrombocytopenia)
    • Fever and infections due to a lack of normal infection-fighting white blood cells (leukopenia)

    Those with acute leukemia may also have signs and symptoms related to accumulations of immature white blood cells, such as:

    • Bone and joint pain
    • Enlarged lymph nodes, spleen, liver, kidneys, and/or testicles
    • Headaches
    • Vomiting
    • Confusion and seizures (when excess cells collect in the brain or central nervous system)
    • Unexplained weight loss
    • Night sweats

    Chronic leukemias often progress slowly and may be found by a health practitioner during a routine check-up before any symptoms are noticed or may cause milder forms of the same symptoms noticed with acute leukemia. Some cases may be monitored for years before they require treatment, while others may be more aggressive. If leukemia cells begin dividing more quickly, they may cause a blast crisis, where leukemia becomes acute, leading to the production of only immature cells and a rapidly worsening condition. Chronic leukemia symptoms include:

    • Feeling tired or rundown
    • Unexplained loss of weight or appetite
    • Shortness of breath during normal physical activity
    • Pale skin
    • Pain or discomfort on the upper left side of the stomach (caused by an enlarged spleen)
    • Night sweats
    • Bleeding easily
    • Fever
  • Tests

    Laboratory Tests
    A number of laboratory tests may be used to help diagnose leukemia, determine the type, and monitor the effectiveness of treatment. After successful treatment (remission), testing may be use to monitor for recurrence of disease.

    Blood tests:

    • Complete blood count (CBC) and WBC differential. These routine tests are ordered to count the number, maturity, and proportion of different types of cells in the blood. These tests can provide the first evidence of leukemia, and they are often the first tests ordered to diagnose leukemia. Irregularities in cell counts, such as elevated white blood cell counts or low red blood cell counts, may be due to leukemia or to a variety of temporary or chronic conditions. But blasts (immature blood cell precursors) are not normally seen in the blood, so if they are present, some kind of leukemia is likely and follow-up testing will be ordered. The CBC and differential are also important tools to monitor the effectiveness of treatment and to detect disease recurrence.
    • Blood smear. A blood smear, or peripheral blood smear, is often used to follow up a CBC with abnormal white blood cells, red blood cells or platelets, or with unclear results. A drop of blood is smeared on a microscope slide and examined for immature cells or cells with abnormal sizes, shapes or appearance compared to normal cells.
       

    Other tests:

    • Bone marrow aspiration/biopsy. Bone marrow is a matrix of fibrous supporting tissue, fluid ("liquid marrow"), undifferentiated stem cells, and a mixture of blasts, maturing and mature blood cells. If a health practitioner suspects that someone has leukemia, a bone marrow aspiration and/or biopsy procedure will be done to look at the fluid and/or tissue in the marrow. In an aspiration, a bone marrow sample is collected from the hipbone, or sometimes the sternum in adults, or the shinbone in infants. A pathologist or other specialist then examines the marrow sample (bone and/or fluid) under the microscope, evaluating the number, size, and appearance of each of the cell types as well as the proportions of mature and immature cells. If leukemia is present, the type and severity of the disease can be determined. This test will also help establish a baseline for bone marrow cells, to see how they respond to treatment.
    • Spinal tap (lumbar puncture) and cerebrospinal fluid analysis. If leukemia is found in the bone marrow, a spinal tap may also be done to look for leukemia cells in the cerebrospinal fluid (CSF). If leukemic cells are seen in the CSF, additional treatment (for example, direct injection of drug into the CSF space) may be necessary.
    • Immunophenotyping or phenotyping by flow cytometry. This test can be used to help diagnose leukemia and to determine which type of leukemia a person has. Cells from the blood, bone marrow, or lymph nodes are incubated with commercially generated antibodies, which selectively bind to antigens on the surface of leukemia cells or in their cytoplasm. The antigens act like markers and are detected by flow cytometry, a type of test that uses a laser beam and a computer to identify cells types based on the antigens present. This process is known as immunophenotyping and helps to categorize the type of leukemia present.
    • Cytogenetic tests (FISH and karyotyping). Cytogenetic tests look at chromosome structure and number. They are used to find abnormal chromosomes associated with leukemias, other cancers, and genetic disorders. They help diagnosis and differentiate leukemias by detecting translocations (where part of a chromosome breaks and reattaches to a different chromosome) for certain acute myeloid leukemias, acute promyelocytic leukemias, chronic myelocytic leukemias, and acute lymphoblastic leukemias, among others. These techniques can also detect deletions associated with acute myeloid leukemia or myelodysplastic syndromes and increases or decreases in the number of chromosomes, such as trisomies (trisomy 12) for chronic lymphocytic leukemia. 
      • Chromosome analysis (karyotyping) is a cytogenetic test that maps the 46 chromosomes in cells to look for changes in arrangement, size, or number (including deletions or translocations) that are associated with leukemia. 
      • Fluorescent in situ hybridization (FISH) is a cytogenetic test that looks for changes in chromosomes that come from genetic variations. It is generally more sensitive than karyotyping. In FISH, an abnormal gene segment in a chromosome is made to "light up" or fluoresce when it is bound by a special probe. FISH helps diagnose different leukemias that may look similar but have different genetic abnormalities and therefore may require different treatment. For more on this, see the article The Universe of Genetic Testing: Cytogenetics (Chromosome Analysis).
    • Polymerase chain reaction (PCR). One factor that contributes to the uncontrolled growth of cancer cells is malfunctioning proteins that control cell growth and development. Those malfunctions can result from abnormalities in DNA from mutations, inversions, fusions, or deletions of parts of the genetic code. The polymerase chain reaction is a laboratory method that amplifies DNA to detect those abnormalities associated with certain types of leukemia. PCR tests can help guide the type or intensity of treatment and/or determine prognosis for a certain leukemia and sometimes identify the target for therapy (targeted therapy) based on the genetic makeup of the cancer cells. Some common PCR tests and their associated leukemia types are:
      • Acute promyelocytic leukemia [PML-RARA ]
      • Acute myeloid leukemia [AML1-ETO, CBFB-MYH11, NPM1 mutation, CEBPA mutation, FLT3 mutation]
      • Acute lymphoblastic leukemia [TEL-AML1, IL3-IGH, BCR-ABL]
      • Myeloid proliferative neoplasm with eosinophilia [FlP1L1-PDGFRA ]
      • Chronic myelogenous leukemia [BCR-ABL ]
      There are also other PCR tests that are used less frequently.
    • Minimum residual disease (MRD) tests. These are relatively new, more sensitive flow cytometry or PCR-based tests to detect very small amounts of leukemic cells post-treatment, known as minimum residual disease (MRD). This can help guide treatment and prevent relapses after the leukemia has gone into remission.
       

    Non-Laboratory Tests
    Computerized tomography (CT), magnetic resonance imaging (MRI), chest x-rays, or positron emission tomography (PET) scans are sometimes used to look for signs of the disease (tumors and masses of cells) in areas such as the chest. Other imaging scans, like ultrasound, may also be used to evaluate the status of body organs such as the spleen, liver, and kidney.

    For more on these, see the web site RadiologyInfo: The radiology information resource for patients.

  • Treatment

    In general, cure and remission rates of leukemia continue to improve for both children and adults.

    Specific treatment depends on the type of leukemia, severity, and symptoms. The goals of treatment are to address the cell shortages that are causing symptoms, induce remission, and, if possible, kill all of the abnormal white blood cells, allowing normal cells to develop and restore normal bone marrow function. Since treatment options are in constant flux, and changing rapidly for some kinds of leukemias, it is important to make individual decisions with a healthcare provider familiar with the most recent research.

    Standard leukemia treatment may include chemotherapy drugs and sometimes radiation, both to kill cells and to relieve pain. If leukemia cells have migrated into the cerebrospinal fluid, chemotherapy drugs that are injected directly into the spinal fluid may be required. Red blood cell and/or platelet transfusions and antibiotic therapy may also be necessary. In chronic leukemias, surgery can be required to remove the spleen if it is too swollen or painful.

    In some cases, it may be necessary to restore healthy bone marrow or stem cells with transplants. Bone marrow samples may be taken from the affected person, "cleaned" of abnormal cells, and frozen to be reintroduced into the same person following treatment, known as an autologous bone marrow transplant, or rescue transplant. Stem cells or bone marrow transplants from a compatible donor are known as allogeneic transplants. Bone marrow transplants may be considered when other treatment regimens have failed to push the leukemia into remission, or when the leukemia has recurred.

    Treatment and prognosis of leukemia depend upon the type of disease. For example, people with CLL do not need chemotherapy until they show symptoms or their red blood cells or platelet numbers decrease. However, allogenic stem cell transplants are the only known potential cure for CLL. Typical treatment for ALL includes long-term chemotherapy. People with AML may need several types of treatment, as soon as possible after diagnosis. This may include chemotherapy followed by a stem cell transplant. Long-term remission can be achieved in people with CML with drugs that are called tyrosine kinase inhibitors (TKI).

    In addition to these treatments, researchers are continuing to investigate new types of therapies to achieve remission and prolong the lives of people with leukemia. A better understanding of how changes in DNA lead to abnormal blood cells is helping researchers develop cancer drugs that inhibit or target specific proteins associated with certain cancers. Tests that detect these genetic abnormalities help health practitioners decide when a person is likely to benefit from these targeted cancer therapies.

    For example, people with CML have a mutation in the BCR-ABL gene sequence, found in an abnormal chromosome, known as the Philadelphia chromosome. Abnormalities in that chromosome lead to the production of an enzyme, tyrosine kinase, which causes uncontrolled growth of leukemia cells. Now, people with CML are generally treated with a TKI, like Imatinib, to impede the growth of cancer cells caused by the Philadelphia chromosome. Tyrosine kinase inhibitors are also used to treat ALL and are being investigated in other types of leukemias, like the drug Ibrutinib for CLL.

    There are a number of other targeted gene therapies available for leukemia, as well as clinical trials for new FDA-approved therapies. Targeted therapies are promising because they are specifically tailored to cancer cells, they are less harmful to normal cells compared to conventional chemotherapy, and thus may be more effective while having less severe side effects. New therapies are being studied alone, in combination, or alongside traditional therapies. Targeted cancer therapies are not without limitations, such as the potential for cancer cells to develop resistance to them. For that reason, targeted therapies may work best in combination with more standard treatments, not as a replacement for them.

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