Leukemias, chronic



Definition

Chronic leukemia is a disease in which abnormal, cancerous white blood cells are made in the bone marrow. Depending on the type of white blood cell that is involved, chronic leukemia can be classified as chronic lymphocytic leukemia or chronic myeloid leukemia.

Description

Chronic leukemia is a cancer that starts in the blood cells made in the bone marrow. The bone marrow is the spongy tissue found in the large bones of the body. The bone marrow makes precursor cells called blasts or stem cells, which mature into different types of blood cells. Unlike acute leukemias , in which the process of maturation of the blast cells is interrupted, in chronic leukemias, the cells do mature and only a few remain as immature cells. However, even though the cells appear normal, they do not function as normal cells.

Bone marrow produces different types of cells: red blood cells (RBCs), which carry oxygen and other materials to all tissues of the body; white blood cells (WBCs), which fight infection; and platelets, which play a part in the clotting of the blood. The white blood cells can be further subdivided into three main types: the granulocytes, monocytes, and the lymphocytes.

The granulocytes, as their name suggests, contain granules (particles). These granules contain special proteins (enzymes) and several other substances that can break down chemicals and destroy microorganisms such as bacteria.

Monocytes are the second type of white blood cell. They are also important in defending the body against pathogens.

The lymphocytes form the third type of white blood cell. There are two main types of lymphocytes: T lymphocytes and B lymphocytes. They have different functions within the immune system. The B cells protect the body by making antibodies, which are proteins that can attach to the surfaces of bacteria and viruses. This attachment sends signals to many other cell types to come and destroy the antibody-coated organism. The T cell protects the body against viruses. When a virus enters a cell, it produces certain proteins that are projected onto the surface of the infected cell. The T cells can recognize these proteins and produce certain chemicals (cytokines) that are capable of destroying the virus-infected cells. In addition, the T cells can destroy some types of cancer cells.

Chronic leukemias develop very gradually. The abnormal lymphocytes multiply slowly, but in a poorly regulated manner. They live much longer and thus their numbers build up in the body. The two types of chronic leukemias can be easily distinguished under the microscope. Chronic lymphocytic leukemia (CLL) involves the T or B lymphocytes. B cell abnormalities are more common than T cell abnormalities. T cells are affected in only 5 percent of the patients. The T and B lymphocytes can be differentiated from the other types of white blood cells based on their size and by the absence of granules inside them. In chronic myelogenous leukemia (CML), the cells that are affected are the granulocytes.

Chronic lymphocytic leukemia (CLL) often has no symptoms at first and may remain undetected for a long time. Chronic myelogenous leukemia (CML), by contrast, may progress to a more acute form.

Demographics

Chronic leukemias account for 1.2 percent of all cancers. Because leukemia is the most common form of childhood cancer, it is often regarded as a disease of childhood. However, leukemias affect nine times as many adults as children. In chronic lymphoid leukemia, 90 percent of the cases are seen in people who are 50 years or older, with the average age at diagnosis being 65. The incidence of the disease increases with age. It is almost never seen in children. Chronic myeloid leukemias are generally seen in people in their mid-40s. In addition, it accounts for about 4 percent of childhood leukemia cases.

Causes and symptoms

Leukemia strikes both sexes and all ages. Although the cause is unknown, chronic leukemia is linked to genetic abnormalities and environmental factors. For example, exposure to ionizing radiation and to certain organic chemicals, such as benzene, is believed to increase the risks for getting leukemia. Chronic leukemia occurs in some people who are infected with two human retroviruses (HTLV-I and HTLV-II). An abnormal chromosome known as the Philadelphia chromosome is seen in 90 percent of those with CML. The incidence of chronic leukemia is slightly higher among men than women.

The symptoms of chronic leukemia are generally vague and non-specific. In chronic lymphoid leukemia (CLL), a patient may experience all or some of the following symptoms:

  • swollen lymph nodes
  • an enlarged spleen, which could make the patient complain of abdominal fullness
  • chronic fatigue
  • a general feeling of ill-health
  • fever of unknown origin
  • night sweats
  • weight loss that is not due to dieting or exercise
  • frequent bacterial or viral infections

In the early stages of chronic myeloid leukemia (CML), the symptoms are more or less similar to CLL. In the later stages of the disease, the patient may experience the following symptoms:

  • non-specific bone pain
  • bleeding problems
  • mucus membrane irritation
  • frequent infections
  • a pale color due to a low red blood cell count (anemia)
  • swollen lymph glands
  • fever
  • night sweats

Diagnosis

There are no screening tests available for chronic leukemias. The detection of these diseases may occur by chance during a routine physical examination.

If the doctor has reason to suspect leukemia, he or she will conduct a very thorough physical examination to look for enlarged lymph nodes in the neck, underarm, and pelvic region. Swollen gums, an enlarged liver or spleen, bruises , or pinpoint red rashes all over the body are some of the signs of leukemia. Urine and blood tests may be ordered to check for microscopic amounts of blood in the urine and to obtain a complete differential blood count. This count will give the numbers and percentages of the different cells found in the blood. An abnormal blood test might suggest leukemia; however, the diagnosis has to be confirmed by more specific tests.

The doctor may perform a bone marrow biopsy to confirm the diagnosis of leukemia. During the bone marrow biopsy, a cylindrical piece of bone and marrow is removed. The tissue is generally taken out of the hip-bone. These samples are sent to the laboratory for examination. In addition to diagnosis, bone marrow biopsy is also done during the treatment phase of the disease to see if the leukemia is responding to therapy.

Standard imaging tests such as x-rays, computed tomography scans (CT scans), and magnetic resonance imaging (MRI) may be used to check whether the leukemic cells have invaded other organs of the body, such as the bones, chest, kidneys, abdomen, or brain.

Treatment

The treatment depends on the specific type of chronic leukemia and its stage. In general, chemotherapy is the standard approach to both CLL and CML. Radiation therapy is occasionally used. Because leukemia cells can spread to all the organs via the blood stream and the lymph vessels, surgery is not considered an option for treating leukemias.

Bone marrow transplantation (BMT) is in the early 2000s becoming the treatment of choice for CML because it has the possibility of curing the illness. BMT is generally not considered an option in treating CLL because CLL primarily affects older people, who are not considered to be good candidates for the procedure.

In BMT, the patient's diseased bone marrow is replaced with healthy marrow. There are two ways of doing a bone marrow transplant. In an allogeneic bone marrow transplant, healthy marrow is taken from another person (donor) whose tissue is either the same or very closely resembles the patient's tissues. The donor may be a twin, a sibling, or a person who is not related at all. First, the patient's bone marrow is destroyed with very high doses of chemotherapy and radiation therapy. To replace the destroyed marrow, healthy marrow from the donor is given to the patient through a needle in the vein.

Chronic lyphocytic leukemia cells, colorized and magnified 400 times. ( 1999 Custom Medical Stock Photo, Inc.)
Chronic lyphocytic leukemia cells, colorized and magnified 400 times.
(© 1999 Custom Medical Stock Photo, Inc.)

In the second type of bone marrow transplant, called an autologous bone marrow transplant, some of the patient's own marrow is taken out and treated with a combination of anticancer drugs to kill all the abnormal cells. This marrow is then frozen to save it. The marrow remaining in the patient's body is then destroyed with high dose chemotherapy and radiation therapy. Following that, the patient's own marrow that was frozen is thawed and given back to the patient through a needle in the vein. This mode of bone marrow transplant is as of the early 2000s being investigated in clinical trials.

In chronic lymphoid leukemia (CLL), chemotherapy is generally the treatment of choice. Depending on the stage of the disease, single or multiple drugs may be given. Drugs commonly prescribed are steroids, chlorambucil, fludarabine, and cladribine. Low dose radiation therapy may be given to the whole body, or it may be used to alleviate the symptoms and discomfort due to an enlarged spleen and lymph nodes. The spleen may be removed in a procedure called a splenectomy.

In chronic myeloid leukemia (CML), the treatment of choice is bone marrow transplantation. During the slow progress (chronic phase) of the disease, chemotherapy may be given to try to improve the cell counts. Radiation therapy, which involves the use of x rays or other high-energy rays to kill cancer cells and shrink tumors, may be used in some cases to reduce the discomfort and pain due to an enlarged spleen. For chronic leukemias, the source of radiation is usually outside the body (external radiation therapy). If the leukemic cells have spread to the brain, radiation therapy can be directed at the brain. As the disease progresses, the spleen may be removed in an attempt to try to control the pain and to improve the blood counts.

In the acute phase of CML, aggressive chemotherapy is given. Combination chemotherapy, in which multiple drugs are used, is more efficient than using a single drug for the treatment. The drugs may either be administered intravenously (through a vein) in the arm or by mouth in the form of pills. If the cancer cells have invaded the central nervous system (CNS), chemotherapeutic drugs may be put into the fluid that surrounds the brain through a needle in the brain or back. This is known as intrathecal chemotherapy.

Biological therapy or immunotherapy is a mode of treatment in which the body's own immune system is harnessed to fight the cancer. Substances that are routinely made by the immune system (such as growth factors, hormones, and disease-fighting proteins) are either synthetically made in a laboratory, or their effectiveness is boosted and they are then put back into the patient's body. This treatment mode in the early 2000s is also being investigated in clinical trials all over the United States at major cancer centers.

Prognosis

The prognosis for leukemia depends on the patient's age and general health. According to statistics, in chronic lymphoid leukemia, the overall survival for all stages of the disease is nine years. Most of the deaths in people with CLL are due to infections or other illnesses that occur as a result of the leukemia.

In CML, if bone marrow transplantation is performed within one to three years of diagnosis, 50 to 60 percent of the patients survive three years or more. If the disease progresses to the acute phase, the prognosis is poor. Less than 20 percent of these patients go into remission.

KEY TERMS

Antibody —A special protein made by the body's immune system as a defense against foreign material (bacteria, viruses, etc.) that enters the body. It is uniquely designed to attack and neutralize the specific antigen that triggered the immune response.

Biopsy —The surgical removal and microscopic examination of living tissue for diagnostic purposes or to follow the course of a disease. Most commonly the term refers to the collection and analysis of tissue from a suspected tumor to establish malignancy.

Chemotherapy —Any treatment of an illness with chemical agents. The term is usually used to describe the treatment of cancer with drugs that inhibit cancer growth or destroy cancer cells.

Computed tomography (CT) —An imaging technique in which cross-sectional x rays of the body are compiled to create a three-dimensional image of the body's internal structures; also called computed axial tomography.

Cytokines —Chemicals made by the cells that act on other cells to stimulate or inhibit their function. They are important controllers of immune functions.

Immunotherapy —A mode of cancer treatment in which the immune system is stimulated to fight the cancer.

Lumbar puncture —A procedure in which the doctor inserts a small needle into the spinal cavity in the lower back to withdraw spinal fluid for testing. Also known as a spinal tap.

Magnetic resonance imaging (MRI) —An imaging technique that uses a large circular magnet and radio waves to generate signals from atoms in the body. These signals are used to construct detailed images of internal body structures and organs, including the brain.

Maturation —The process by which stem cells transform from immature cells without a specific function into a particular type of blood cell with defined functions.

Radiation therapy —A cancer treatment that uses high-energy rays or particles to kill or weaken cancer cells. Radiation may be delivered externally or internally via surgically implanted pellets. Also called radiotherapy.

Remission —A disappearance of a disease and its symptoms. Complete remission means that all disease is gone. Partial remission means that the disease is significantly improved, but residual traces of the disease are still present. A remission may be due to treatment or may be spontaneous.

Prevention

Most cancers can be prevented by changes in lifestyle or diet, which will reduce the risk factors. However, in leukemias, there were as of 2004 no known risk factors. Therefore, as of 2004, there was no way known to prevent the leukemias from developing. People who are at an increased risk for developing leukemia because of proven exposure to ionizing radiation, the organic liquid benzene, or people who have a history of other cancers of the lymphoid system (Hodgkin's lymphoma) should undergo periodic medical checkups.

Parental concerns

Parents of a child with leukemia must balance their own fears for their child's health with the child's fears and worries. Also, given the large financial burden leukemia treatment entails, parents will want to make sure they are aware of what and what is not covered by their insurance. Parents can find a variety of sources, written and online, that will help them deal with the new circumstances of themselves and their family .

Resources

BOOKS

Cheson, Bruce D. "Chronic Lymphoid Leukemias." In Clinical Oncology. Edited by Martin D. Abeloff. London: Churchill Livingstone, 2000.

——. "Chronic Myeloid Leukemias." In Clinical Oncology. Edited by Martin D. Abeloff. London: Churchill Livingstone, 2000.

Tubergen, David G., and Archie Bleyer. "The Leukemias." In Nelson Textbook of Pediatrics. Edited by Richard E. Behrman et al. Philadelphia: Saunders, 2004.

ORGANIZATIONS

American Cancer Society. 1599 Clifton Rd., NE, Atlanta, GA 30329–4251. Web site: http://www.cancer.org.

Cancer Research Institute. 681 Fifth Ave., New York, NY 10022. Web site: http://www.cancerresearch.org.

Leukemia Society of America Inc. 600 Third Ave., New York, NY 10016. Web site: http://www.leukemia.org.

National Cancer Institute. Building 31, Room 10A31, 31 Center Drive, MSC 2580, Bethesda, MD 20892–2580. Web site: http://www.nci.nih.gov.

Lata Cherath, PhD Rosalyn Carson-DeWitt, MD



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