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Medical Specializations


Pathology => Blood => Leukemia


Leukemia


INTRODUCTION
Leukemia, any of several types of cancers that affect blood cells, including oxygen-carrying red cells; certain infection-fighting white cells, such as granulocytes, macrophages and lymphocytes; and platelets, which aid in blood clotting. According to the American Cancer Society, leukemia is the sixth leading cause of cancer deaths among men and the seventh leading cause of cancer deaths among women. It accounts for about one-third of all cancer deaths in children. Over 28,500 new cases of leukemia are diagnosed in the United States each year.

Blood cells are made in the bone marrow, the spongy tissue in the center of bones. A leukemia begins when an immature blood cell in the marrow, known as a progenitor cell, becomes cancerous, dividing uncontrollably and overriding the body's normal restrictions on cell division. Over time, the marrow becomes crowded with cancerous cells, all of them descendants of the first abnormal cell. The malignant cells may also accumulate in a patient's lymph nodes, spleen, and elsewhere. At the time of diagnosis, up to a trillion leukemic cells may be present in the body.

The mass of leukemic cells in the marrow suppresses the production of healthy blood cells, giving rise to the symptoms typical of leukemia. Pale skin, fatigue, and shortness of breath are signs of anemia, a decrease in the concentration of red cells in the blood. Nose bleeds, gum bleeding, a tendency to bruise easily, and pinhead-sized red spots on the skin reflect the decrease in the concentration of platelets in the blood. A lack of functional white cells makes patients with leukemia prone to infection.
Leukemia was first described by European physicians during the mid-19th century. During autopsies, physicians noted cases of profoundly elevated white cell counts-today we know that many of these white cells were nonfunctional leukemic cells-and very low red cell counts. For this reason, the condition was referred to as weisses blut (German for "white blood"). Later, the term leukemia (Greek leukos, "white"; haima, "blood") was applied to the disease.

TYPES OF LEUKEMIA
The leukemias are classified by two principal characteristics: the lineage of blood cell that becomes cancerous, and how rapidly the disease progresses. A leukemia is classified as myelocytic or myelogenous if the malignant cells have descended from the progenitors of red cells, granulocytes, macrophages, or platelets. If the leukemic cells have descended from a lymphocyte precursor cell, the leukemia is referred to as lymphocytic.

Myelocytic or lymphocytic leukemia can be acute or chronic, terms that refer to the patient's life expectancy if the disease remains untreated. Acute leukemias develop rapidly, and without prompt treatment, the suppression of normal blood cell production is so severe that death occurs in a matter of weeks. In the chronic leukemias, patients may survive for several years or more without treatment because the effects of leukemic cells on the structure and function of the marrow develop more slowly and are less severe. In chronic myelocytic leukemia, for example, the leukemic cells can often complete their development and become functional blood cells. In chronic lymphocytic leukemia, the leukemic lymphocytes do not function normally, but in many cases the abnormal cells do not severely inhibit normal blood cell development.

The four major forms of leukemia-acute myelocytic, chronic myelocytic, acute lymphocytic, and chronic lymphocytic-can be further subcategorized based on the appearance of the malignant cells, the presence of characteristic molecules on their surface, or their stage of development. For example, hairy-cell leukemia is an uncommon type of chronic lymphocytic leukemia in which the malignant cells have fine, hairlike projections on their surface.
Myelocytic leukemia-both acute and chronic forms-can occur at any age, but more than 90 percent of cases occur in adults, and the risk of developing the disease increases dramatically after the age of 50. Acute myelocytic leukemia is the most common form of leukemia in the United States, with 9400 new cases diagnosed each year. About 4300 new cases of chronic myelocytic leukemia are diagnosed each year.

Chronic lymphocytic leukemia occurs rarely before the age of 45 and increases in incidence with each succeeding decade. Acute lymphocytic leukemia, by contrast, can occur at any age, but about half the cases occur in children under the age of 19, with the peak incidence occurring at about 4 years of age. In the United States, chronic lymphocytic leukemia accounts for about 7300 new cases of leukemia each year, and acute lymphocytic leukemia, for about 3100 new cases.

CAUSES
In most cases of leukemia, the cause is unknown, but physicians have identified four known causes of certain types of leukemia. Intensive radiation exposure or moderately intense exposure for long periods increases the risk of acute and chronic myelocytic leukemia and acute lymphocytic leukemia, but not chronic lymphocytic leukemia. The high rate of leukemia among Japanese survivors of the atomic bomb detonations at Hiroshima and Nagasaki at the end of World War II dramatically demonstrated the role of radiation in causing leukemia.
Exposure to certain chemicals can also cause leukemia. Workers exposed to benzene over long periods have an increased risk of developing acute myelocytic leukemia. Chemotherapy drugs used to treat breast cancer, ovarian cancer, lymphomas, and certain other cancers also increase a patient's risk of later developing acute myelocytic leukemia.

Two viruses, human T-cell leukemia viruses (HTLV) I and II, are known to cause T-cell leukemia, a very rare form of lymphocytic leukemia, in humans. However, only a small percentage of people who are infected with these viruses develop cancer. Although virus-related leukemia is rare in humans, it is quite common in other animal species, such as cats, chickens, and mice.
Genetic factors may also contribute to the development of leukemia. Some inherited conditions, such as Down syndrome, increase a person's risk of developing leukemia. In addition, scientists have identified rare clusters of leukemia in several members of the same family, presumably due to an inherited genetic mutation.

DIAGNOSIS
Bone marrow biopsy and blood tests are the primary techniques used to diagnose leukemia. In a bone marrow biopsy, cells are collected through a hollow needle inserted into the outer edge of a hipbone, or a small cylinder of bone containing marrow is removed with a special needle. The marrow sample is examined with a microscope for the presence of leukemic cells.
Blood tests that monitor blood cell counts-the number of cells of different types in the blood-can also reveal abnormalities characteristic of various forms of leukemia. Patients with acute leukemias nearly always have decreased red cell and platelet counts. In some patients, white cell counts are also very low. In others, a large number of leukemic cells enter the blood from the bone marrow, making white cell counts very high. However, physicians can examine these cells under the microscope to determine that they are abnormal, leukemic cells, not healthy white cells, and that the elevated white cell count is not due to another cause, such as infection.

Patients with chronic leukemias usually have slightly decreased red cell counts. Platelet counts are usually normal or mildly increased in patients with chronic myelocytic leukemia, and normal or mildly decreased in chronic lymphocytic leukemia. Nearly all chronic leukemia patients have increased white cell counts. In chronic myelocytic leukemia, some of these white cells are healthy, infection-fighting cells, but in chronic lymphocytic leukemia the blood contains large numbers of malignant lymphocytes that do not function normally.

Sometimes additional tests, such as staining of cells with various chemical dyes to help doctors examine their appearance, analysis of molecules on the surface of the cells, and analysis of the cells' genetic material, are performed on leukemic cells collected from the marrow or blood. These tests help doctors determine the subcategory of leukemia, which, in turn, may affect a patient's prognosis and the approach to treatment. Tests such as chest X rays and examination of the spinal fluid for leukemic cells can help doctors determine how far the disease has spread.

TREATMENT
Treatment of leukemia depends on the type and extent of the disease and is tailored to each individual patient. In general, chemotherapy-the use of drugs that kill rapidly dividing cells-is the mainstay of treatment for both acute and chronic leukemias. In acute leukemias, chemotherapy is very intensive and uses several drugs, either simultaneously or sequentially, in order to kill as many leukemic cells as possible. Antibiotics and transfusions of red cells and platelets help sustain patients whose blood counts are dangerously low because they are receiving intensive chemotherapy.
Sometimes radiation is used to shrink collections of leukemic cells that accumulate in various parts of the body, such as on the lining of the brain and spinal cord in acute lymphocytic leukemia, or within lymph nodes in chronic lymphocytic leukemia. If left untreated, collections of cells on the lining of the brain and spinal cord can cause headache, blurred vision, and confusion, and elsewhere in the body can cause swelling and tenderness of the affected area.

Particularly in young patients, if doctors determine that chemotherapy alone is not likely be successful or if patients relapse after chemotherapy, stem cell transplantation may be performed. In this procedure, very intensive total body radiation or very high doses of chemotherapy or both are used. The chemotherapy and radiation are designed to destroy all the leukemic cells in a patient's body; however, this treatment also destroys the blood-forming system in the patient's bone marrow. For this reason, healthy stem cells, the cells in bone marrow that enable long-term formation of blood, must then be infused into a patient to replenish the blood-forming system. The stem cells must come from an immunologically matched donor, usually a sibling or other close relative. Formerly, stem cells could only be transplanted from the bone marrow of the donor, and the procedure was known as bone marrow transplantation. Recent advances now make it possible to recover stem cells from circulating blood, making the transplant procedure much simpler and less risky for the donor.

Immunotherapy, though still in the experimental stages, is a promising new approach to treating leukemia. In this technique, highly specific molecules known as monoclonal antibodies are manufactured in the laboratory to target molecules on the surface of leukemic cells. The antibodies are attached to a radioactive substance, then injected intravenously into a patient. This method provides a convenient means of delivering the radioactive substance directly to leukemic cells, where it may kill these cells with minimal effect on healthy cells.

The goal in treating acute leukemias is to kill enough leukemic cells to produce a remission, meaning that the production of healthy blood cells is no longer suppressed, blood cell counts return to normal, and the patient's symptoms diminish. At that stage, further therapy is used to try to prolong remission or achieve a cure. About 75 percent of children with acute lymphocytic leukemia are cured. Cure rates in acute myelocytic leukemia are estimated to be about 30 percent in children and somewhat lower in adults. In the chronic leukemias, cures are very infrequent, but today's chemotherapy regimens have increased the average survival in these patients from about three years to about six years. In elderly patients who develop chronic leukemia, life expectancy may not be reduced at all.

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