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February 4, 2002

Leukemia Introduction
In Memorium
Barbara Lackritz
June 4, 2003

Acute Lymphocytic Leukemia (ALL)
Acute Myelogenous Leukemia (AML)

Chronic Myelogenous Leukemia (CML)
Chronic Lymphocytic Leukemia
Hairy Cell Leukemia (HCL)

Approximately 142,000 people are currently afflicted with leukemia. Another 30,200 cases will be diagnosed in the United States this year and approximately 22,100 individuals will die from the disease. There are two major kinds of leukemia: chronic and acute. About half of all leukemia patients suffer from the acute types, while half are afflicted with the chronic types. Most cases of leukemia occur in older adults, with more than half of all cases occurring in people over 60. Nevertheless, more younger adults are being diagnosed with leukemia, perhaps because of the greater use of blood testing in current medical practice.

Acute leukemia is a rapidly progressing disease that affects red and white blood cells and platelets (cells that allow the blood to clot) that are not yet fully developed, meaning these cells cannot carry out their normal functions. This type of leukemia is divided into two categories, depending on the cell type involved. If the disease involves the lymphocytes it is called acute lymphocytic leukemia, but if it affects the myelocytes ( immature cells that become metamyelocytes) it is known as acute myelogenous leukemia.

Acute lymphocytic leukemia (ALL) is the most common form of the disease in children, while acute myelogenous leukemia (AML) occurs mostly in older people. Leukemia is the leading cause of death from disease in children under age 15, with approximately 2,300 new cases of ALL being diagnosed among youngsters ages 0 to 14 this year. Leukemia affects 10 times as many adults as children, but it is rapidly becoming more curable in children than in adults as greater resources are being expended in that effort.

Chronic leukemia progresses more slowly and permits greater numbers of fully developed blood cells to grow, allowing these cells to carry out some of their normal functions. This type of leukemia is also divided into two major types. Chronic lymphocytic leukemia (CLL) and chronic myelogenous leukemia (CML) mostly affect older adults.

Acute Lymphocytic Leukemia (ALL)
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About 3,500 new cases of acute lymphocytic leukemia are diagnosed each year in the United States. This form of the disease differs from other types of leukemia, in which older people are more likely to develop the disease. The risk of developing ALL is greatest in young children, peaking at 4 years of age. The risk then decreases until age 50, when it rises again, especially among men.

Subtypes of Acute Lymphocytic Leukemia

Classifying a subtype of leukemia helps doctors choose the best course of therapy for each patient by helping them delineate a patient's risk level and best response to treatment.

Three subtypes of ALL can be identified under a microscope: L1 (small), L2 (large) and L3 (large with other features). These cells are further classified according to whether they resemble B lymphocytes or T lymphocytes. In most children, cells are designated as L1 and are related to B lymphocytes, whereas in adults cells are defined as L2. B lymphocytic subtypes account for about 85 percent of ALL cases, while T lymphocytic subtypes account for 15 percent of cases.

Abnormalities of chromosomes may also aid doctors in identifying a subtype of ALL. For example, a change in chromosome 22, known as the Philadelphia chromosome, occurs in a small percentage of children and a greater percentage of adults with ALL. This means that adults would have a higher risk of developing a more aggressive form of the disease, so their treatment would be intensified. often take antibiotics to treat such infections.

Acute Myelogenous Leukemia (AML)
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Acute myelogenous leukemia is the most common type of the disease in adults. It is estimated that 10,100 new cases will be reported each year. Older people are more likely to develop AML than children. In fact, the risk for developing the disease increases from age 30 (1 case per 100,000) to age 70 (1 case per 10,000). The overall survival rate for children is 43 percent, compared to only 14 percent for adults.

AML Subtypes

The subtypes of AML are classified based on the stage of development myeloblasts have reached at the time of diagnosis.

If immature myeloblasts are the dominant cells at the time of diagnosis, the leukemia is referred to as "myeloblastic" type. If there are many myeloblasts, but some cells are beginning to develop into mature cells, the designation "with maturation" is added. If cells are developing features of monocytes, the term monocytic is applied. For those that are developing characteristics of red cells, erythroleukemia is used. Megakaryocytic leukemia cells may show a "budding" of the cytoplasm.

(Designation) -

Chronic Myelogenous Leukemia (CML)
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About 4,300 cases of chronic myelogenous leukemia are diagnosed in the United States each year. CML occurs primarily in adults, and accounts for only 4 percent of childhood leukemia cases. The frequency of the disease increases with age from about one in a million children in the first 10 years of life to one in 100,000 people at age 40, to one in 10,000 people by age 80 and above. The disease progresses in a similar fashion in children and adults.

CML results from an acquired (not inherited) injury to the DNA of a stem cell in the marrow. This leads to an uncontrolled growth of white blood cells, which accumulate in massive amounts in the blood. Unlike the acute form of the disease, chronic myelogenous leukemia allows the development of mature white blood cells that can perform their functions normally.

Chronic myelogenous leukemia is distinguished from other leukemias by the presence of an acquired genetic abnormality in blood cells called the Philadelphia chromosome, also known as chromosome 22. Chromosome 9 is also abnormal in CML patients. Pieces of these genes break off and switch with each other in a process called translocation. The mutation that is formed as a result is called the BCR-ABL gene. In CML patients, the BCR-ABL gene produces an abnormal or mutated protein, which is responsible for converting the marrow stem cell from normal to leukemic.

Chronic Lymphocytic Leukemia
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Nearly 7,300 people are diagnosed with chronic lymphocytic leukemia (CLL) in the United States each year. This form of the disease differs from the others in two ways; it has not been linked to radiation or benzene exposure and family history of the disease is associated with an increased risk.

First degree relatives of patients with CLL have a 30 percent greater likelihood of getting the disease than other people. The disease is considered uncommon in people under 45 years of age, but many are still diagnosed with CLL. Statistics still imply that 67 percent of patients who receive a CLL diagnosis are over age 60 and the incidence of the disease increases dramatically thereafter.

CLL results from an acquired (not inherited) injury to the DNA of a single cell in the bone marrow. The outcome of this injury is the uncontrolled growth of lymphocytic cells in the marrow that leads to an increase in the number of lymphocytes in the blood. The lymphocytes do not die as they would if they were normal, instead they remain alive crowding the bone marrow until they force out healthy, needed blood cells. The fact that the cells all arise from a single cell clone is a key factor in diagnosing CLL.

CLL may have little effect on a person's well-being at first. Symptoms, including fatigue and shortness of breath, develop gradually. Patients may also lose weight or experience recurrent infections of the skin, lungs, kidneys or other sites. Lymph nodes may enlarge.

The disease is sometimes discovered during a routine medical examination, when a blood test may reveal an elevated white cell count. This commonly leads physicians to consider a diagnosis of CLL. Large numbers of lymphocytes can collect in the lymph nodes, which may become enlarged.

As with other forms of leukemia, a diagnosis of CLL is confirmed using a sophisticated blood test known as flow cytometry. Sometimes it is still diagnosed with a blood and bone marrow biopsy and aspiration. A high white cell count is almost always present in the blood, while platelet and red blood cell counts are only slightly affected in the early stage of the illness. A bone marrow examination will show a substantial increase in the number of lymphocytes in the marrow, and a decrease in the amount of normal marrow cells. Doctors check the pattern of the CLL cells in the bone marrow to tell how advanced the disease may be.

Another test that helps doctors decipher how CLL will progress is immunophenotyping. This technique reveals the type of lymphocytes present in the blood of CLL patients. The T cell type of CLL is less frequent and affects the skin, nervous system, and lymph nodes more often and progresses more rapidly than the B cell type.

The measurement of gamma globulins (immunoglobulins) is important in CLL patients. These antibodies are deficient in people with the disease, causing them to be susceptible to infections.

CLL is also the only form of leukemia that is formally staged. The most common systems used are the Rai and/or Binet systems. The Rai staging system is the most widely used in the United States, whereas the Binet system is commonly used in Europe.

CLL, in 3 to 10 percent of cases, changes (transforms) into an aggressive form of diffuse large cell lymphoma called Richter's Syndrome. It is a form of non-Hodgkin's lymphoma that is difficult, but not impossible to treat. We do not yet know why this happens.

In addition, CLL cells sometimes develop into larger cells called prolymphocytes, resulting in a diagnosis of prolymphocytic leukemia (PLL) It is also possible for patients who have never had CLL to be diagnosed with PLL.

Hairy Cell Leukemia (HCL)
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Hairy cell leukemia is also a disease of the lymphocytes. It accounts for only 2 percent of the leukemias. The disease received its name because the lymphocytes have short, thin projections from their surface that look like hairs when examined under a microscope. The hairy cells accumulate in the bone marrow and spleen and even in the lymph nodes.

There are no known risk factors for hairy cell leukemia. Environmental and genetic risks have not been linked to the disease.

The symptoms of hairy cell leukemia can be general and resemble other illnesses. Patients may feel discomfort on the upper left side of their abdomen because of an enlarged spleen. They may also experience weight loss and a loss of general well-being.

Complications may result from decreased blood cell counts, including anemia (low red cell count), thrombocytopenia (deficiency of platelets) and an increased risk of infection (deficiency of white cells). Unexplained bruising may be the result of a platelet deficiency. Patients may experience a fever or chills, indicating an infection.

Hairy cell leukemia is diagnosed using blood tests, a bone marrow biopsy and immunophenotyping. CT scans can be used to detect the enlargement of abdominal lymph nodes and the spleen.

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February 4, 2002

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