Acute myelogenous leukemia (AML, also sometimes called acute myeloid leukemia or acute nonlymphocytic leukemia) is a malignancy that arises in either granulocytes or monocytes, white blood cells that battle infectious agents throughout the body.
Risk factors for different types of cancer are those traits that increase the likelihood that an individual will develop disease. Risk factors include certain kinds of behavior such as smoking, inherited (genetic) traits, and exposure to cancer-causing agents in the environment. There is only a very small chance that a person who has one of the few known risk factors for AML will develop the disease.
Cigarettes, which contain dozens of cancer-causing chemicals, are most often implicated in the development of solid tumors such as those of the lung, bladder, and head and neck, but smoking is also believed to be a risk factor for leukemia. Researchers estimate that about 20 percent of AML cases are related to smoking.
People who are exposed to high doses of radiation (from the explosion of an atomic bomb, by working in an atomic weapons plant, or from a nuclear reactor accident) have a heightened risk of developing leukemia. This is also true of people who are exposed over long periods of time to high levels of solvents such as benzene in the workplace.
People who have received previous chemotherapy or radiation treatments for cancer have an increased risk of developing leukemia, as the chemotherapeutic agents and radiation target rapidly dividing cells such as those of the bone marrow. These agents can cause mutations, or changes in a cell's DNA, that can lead to later malignancies including leukemia. AML is linked to treatments for Hodgkin's disease, non-Hodgkin's lymphoma, childhood acute lymphocytic leukemia, and to treatment for other malignancies such as breast and ovarian cancer.
People who have a myelodysplastic syndrome, a preleukemia condition, or who have rare genetic syndromes such as Down's syndrome, Fanconi's anemia, ataxia-telangiectasia, and Bloom's syndrome are at slightly higher risk of developing leukemia.
Many people with one or more of these risk factors never develop leukemia. And most of the people who do develop AML have no risk factors at all. Scientists do know that most leukemias are associated with specific gene mutations, but, in most cases, it is not clear what causes those mutations.
The symptoms of acute leukemia generally appear suddenly and can be similar to those of a virus or flu. They can be severe enough that they prompt patients see their physicians shortly after their onset, and include:
These symptoms are associated with a wide range of conditions and illnesses other than leukemia. But if these problems persist, consult a physician.
Physicians perform an array of tests to help diagnose leukemia and determine its type and specific subtype. The tests help determine if there are changes in the amounts of different kinds of circulating blood cells, if the cells have an abnormal appearance when seen through a microscope, if there are changes in the cellular makeup of the bone marrow, to determine what changes have taken place in the genetic and molecular makeup of the diseased cells, and to discover any other factors that are helpful in deciding on the most effective course of treatment.
Blood tests can show whether the amounts of various components of blood are within normal ranges. In leukemia, red blood cell levels may be low, causing anemia; platelet levels may be low, which can cause bleeding and bruising, and white blood cell levels may be diminished, leading to infections.
Bone marrow aspirates and biopsiesare used to determine the number of blasts, or immature cells, in the marrow. Normally, blasts account for less than 5 percent of bone marrow content. In patients with leukemia, blasts increase to between 30 and 100 percent of marrow. In a bone marrow biopsy, physicians use a hollow needle inserted into the hip bone to remove a piece of marrow and bone for examination. In a bone marrow aspirate, a small sample of liquid bone marrow is withdrawn through a syringe.
If diseased cells are found through the bone marrow biopsy or aspirate, physicians will also perform a lumbar puncture, or spinal tap, to see if the disease has spread into the cerebrospinal fluid, which surrounds the central nervous system (CNS) -- the brain and spinal cord.
In addition, physicians use a number of tests that help them determine specific features of the cells in biopsied tissue including genetic abnormalities such as chromosomal rearrangements -- which are common in leukemias -- and whether the cells have specific proteins (antigens) on their surfaces; this information helps both identify the cells' origins and determine the patient's prognosis. These tests include the following:
Physicians sometimes use imaging tests to determine whether AML has affected the bones or the organs such as the kidneys or brain, or the lymph nodes. These tests can include chest x-rays, ultrasound, computed tomography (CT scan), and magnetic resonance imaging (MRI).
Physicians devise a course of treatment for each AML patient that takes a number of factors into consideration: the AML subtype; whether the patient has been treated already, with what, and how successfully; the number of leukemic cells detectable in the blood; which chromosomal alterations are present; and the patient's age and overall health. For this reason, AML patients with the same disease subtype may receive different treatments.
The standard treatment approaches for adult leukemia are chemotherapy, immunotherapy, and bone marrow transplantation. Radiation therapy -- treatment with high-energy rays that destroy cancer cells -- is sometimes used for leukemia in the central nervous system or elsewhere. But because leukemia is systemic, surgery is almost always ineffective.
Treatment for AML is typically divided into two phases: remission induction and post-remission therapy.
The goal of the remission induction phase is to induce a remission, a state in which there is no visible evidence of disease and blood counts are normal. Patients may receive a combination of drugs during this phase including daunorubicin, idarubicin, or mitoxantrone plus cytarabine and thioguanine.
In the next phase, the post-remission therapy phase, patients may receive high doses of chemotherapy, designed to eliminate any remaining leukemic cells. During this phase, treatment may include a combination of two or more of the agents cytarabine, daunorubicin, idarubicin, etoposide, cyclophosphamide, mitoxantrone, or cytarabine.
A stem cell or bone marrow transplant is an option for some AML patients; this procedure is done after an initial remission is achieved. In this procedure, bone marrow or stem cells -- blood-forming cells -- are filtered from the patient's (autologous transplantation) or a donor's (allogeneic transplantation) marrow or bloodstream and then frozen. The patient then receives a high dose of chemotherapy, which destroys tumor cells but also damages the stem cells in the patient's bone marrow. The harvested stem cells or marrow are then administered, or transplanted, to help rebuild the patient's immune system.