Leukemia

Risk: Risk factors for leukemia include exposure to high levels of radiation (such as a nuclear event or massive doses of radiation treatment, but not diagnostic x-rays or radiation from electromagnetic fields) and to chemical or environmental carcinogens such as benzene, formaldehyde, and petrochemicals. Smokers have a small increased risk of developing AML compared to nonsmokers (Seiter, "AML"). Receiving chemotherapy to treat a previous cancer can increase the risk of developing leukemia; for example, in patients with breast cancer who received specific chemotherapeutic agents, acute myelogenous leukemia was diagnosed in 0.2% to 1.0% of individuals in the first five years after treatment (Seiter, "AML"). However, most cases of leukemia develop with no identifiable link to a risk factor.

Individuals with a history of aplastic anemia or other blood disorders (antecedent hematologic disorders), or diseases of the bone marrow such as myelodysplastic syndromes (MDS), are at greater risk of developing acute myelogenous leukemia (Seiter, "AML").

Individuals with certain chromosomal abnormalities such as Down syndrome or Klinefelter's syndrome are at increased risk of developing leukemia. Abnormal gene expression related to certain chromosomal changes (translocations) may also increase the risk of adults developing ALL, AML, or CML. Familial syndromes related to gene mutations, and hereditary cancer syndromes such as Li-Fraumeni syndrome, can also predispose individuals to developing AML (Seiter, "AML").
CLL primarily affects middle-aged to elderly adults, including about 30% who are younger than age 65, with increasing incidence over age 65; risk is increased in about 5% to 10% of individuals with a family history of the disease, and whites are affected slightly more than blacks (Grever). ALL is most common in children and develops less commonly in adults between the ages of 30 and 60 (Seiter, "ALL"). The risk of AML increases with age; this type of leukemia affects primarily older adults, with a median age of 70 (Seiter, "AML"). CML primarily affects middle-aged adults. Regardless of type, leukemia affects males at nearly twice the rate of females; however, in AML, the risk is only slightly higher for men than for women (Seiter, "AML"). The risk of a subtype of AML known as acute promyelocytic leukemia (APL) is higher in younger adults (median age 31) and in Hispanics, especially those who have a coagulation disorder (Freireich).

Incidence and Prevalence: In 2007 in the US there were an estimated 7,060 cases of AML in men and 6,350 in women, or about 13,400 new cases of this type of leukemia (Seiter, “AML”). ALL occurs most commonly in children, but about 1,000 new cases of ALL are diagnosed annually in adults (Seiter, “ALL”).

Approximately 4,400 new cases of CML and 10,000 new cases of CLL are diagnosed annually, including about 5,280 in men and 3,740 in women (Grever).

AML is diagnosed primarily in developed countries around the world. The highest incidence of ALL is reported in Italy, Switzerland, and Costa Rica.

History: In acute leukemia, symptoms appear and get worse quickly, sometimes in just a few days or within one or two weeks before diagnosis. Other individuals may develop symptoms over a period of months. Individuals with this disease go to their doctor because they feel sick. They may have noticed general symptoms, such as weight loss, loss of appetite, headache, dizziness, fatigue, or frequent infection. In chronic leukemia, symptoms may not appear for a long time, and when they do appear, they are generally mild at first and worsen gradually.

Chronic leukemia is generally discovered during a routine checkup before there are any symptoms. Symptoms may include generally feeling ill (malaise); fever, chills, and other flu-like symptoms; night sweats; weakness and fatigue; weight loss; loss of appetite; abdominal pain; vomiting; frequent infections; easy bleeding and bruising; severe nosebleeds and swollen or bleeding gums; shortness of breath; bone and joint pain; blurred vision and difficulty maintaining balance; and/or seizures.

Physical exam: Individuals may present with gum enlargement, enlarged and tender lymph nodes most often in the underarms, groin, or neck areas; and an enlarged liver (hepatomegaly) and/or spleen (splenomegaly), indicating organ infiltration with leukemic cells. If reduced platelets (thrombocytopenia) or other coagulation problems are present, tiny pinpoint red spots (petechiae) or larger purple discolorations (purpura) under the skin may be found, especially on the lower extremities. Fever and other signs of infection, including signs of pneumonia, may be present. If anemia is present, individuals may appear pale, and the reduced numbers of red blood cells and reduced delivery of oxygen to tissues may cause shortness of breath. In AML, a cardiac flow murmur may be present as a sign of bone marrow failure. Respiratory distress and alterations in mental state may be noted as signs of organ infiltration by leukemic cells.

Tests: Although blood tests may reveal that an individual has leukemia, they may or may not show what type of leukemia it is. A complete blood count (CBC) with differential (peripheral blood smear) will show abnormalities consistent with leukemia, including the number, appearance, and maturity of WBCs. The number of cells that are blasts (immature white blood cells) is especially important to diagnosis; if more than one-third of cells are blasts, it confirms a diagnosis of acute leukemia. Blasts can represent 90% of cells in a peripheral smear when the WBC count is significantly higher than normal (Freireich). The RBC count, hemoglobin, hematocrit, and platelet count may be decreased. Blood chemistries will also be performed to help determine related liver or kidney problems and to serve as a baseline for comparison during eventual treatment and disease monitoring.

Bone marrow aspiration and biopsy are usually performed to identify marrow cells and determine the type of leukemia. A sample of bone marrow is removed with a needle (bone marrow aspiration) and examined under the microscope. A bone marrow biopsy, performed with a larger needle, involves removing a small piece of bone and bone marrow together. The number of blast cells in bone marrow can range between 20% and 90% (Freireich). If leukemia cells are found in the bone marrow sample, a spinal tap (lumbar puncture) may be performed to check for leukemia cells in the fluid that fills the spaces in and around the brain and spinal cord (cerebrospinal fluid).

Cytochemistry techniques are used to examine cells microscopically after they have been stained using special stains. By highlighting cell characteristics, such as granules or abnormal shapes and sizes, specific types of WBCs can be identified in peripheral blood, bone marrow, cerebrospinal fluid, and lymph gland samples to help confirm the diagnosis. Flow cytometry may also be used to examine cells obtained from the blood, the bone marrow, or lymph glands and to determine their immunophenotypes. This technique treats cells with certain antibodies and examines them with laser beams. Because each antibody only adheres to specific antigens on cell surfaces, the method can identify cell types to accurately determine the type of leukemia.

Chromosomal studies on bone marrow samples (cytogenetic studies) provide further information. A variety of familial and acquired chromosome abnormalities are associated with the diagnosis and prognosis of leukemia.

Genetic profiling of leukemic cells can help identify mutated genes that may indicate a more favorable or less favorable clinical course in individuals with CLL. Genetic abnormalities can be detected using fluorescent in situ hybridization (FISH) analysis; more than 80% of individuals with CLL are found to have specific biomarkers on leukemic cells that predict a better response to therapy (Grever).

Human leukocyte antigen (HLA) and DNA typing may be done if an individual is being considered for bone marrow transplantation.

Chest x-rays may be performed to evaluate possible lung or cardiac involvement. Imaging studies such as computed tomography scanning (CT) may be used only to evaluate lymph gland involvement and organs that may be affected. Ultrasound is also sometimes used to visualize changes in the kidneys, liver, or spleen. In types of leukemia in which the lymph glands may be affected, such as CLL, biopsies of lymph nodes may be done to examine lymph cells. Multiple gated acquisition (MUGA) scans are performed in individuals with confirmed AML because of a high likelihood of heart problems associated with use of cardiotoxic chemotherapy agents (Seiter, “AML”). Electrocardiography may also be performed before treatment is recommended.