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Acute Myelocytic Leukemia (AML)

by Michael E. Rytting, MD

Acute myelocytic (myeloid, myelogenous, myeloblastic, or myelomonocytic) leukemia is a life-threatening disease in which the cells that normally develop into neutrophils, basophils, eosinophils, and monocytes become cancerous and rapidly replace normal cells in the bone marrow.

  • People may be tired or pale, may be easily susceptible to infection and fever, and may bruise or bleed easily.

  • Blood tests and bone marrow examination are needed for diagnosis.

  • Treatment includes chemotherapy to achieve remission plus additional chemotherapy to avoid relapse.

Acute myelocytic leukemia (AML) is the most common type of leukemia among adults, although it affects people of all ages. AML sometimes is caused by chemotherapy or radiation therapy given to treat another cancer.

In AML, immature leukemia cells rapidly accumulate in the bone marrow, destroying and replacing cells that produce normal blood cells. The leukemia cells are released into the bloodstream and are transported to other organs, where they continue to grow and divide. They can form small masses (chloromas) in or just under the skin or gums or in the eyes.

There are several subtypes of AML, which are identified based on characteristics of the leukemia cells. Acute promyelocytic leukemia is an important subtype of AML. In this subtype, chromosomal changes in promyelocytes—cells that are at an early stage in the development into mature neutrophils—allow accumulation of these immature cells. The underlying abnormality is in the metabolism of retinoic acid.

Symptoms and Diagnosis

The first symptoms of AML are very similar to those of acute lymphocytic leukemia (see Acute Lymphocytic Leukemia (ALL)). The gums may be inflammed and swollen. Although meningitis occurs less often than in acute lymphocytic leukemia, AML cells can cause inflammation of the layers of tissue covering the brain and spinal cord (meninges).

The diagnosis of AML is also similar to that of acute lymphocytic leukemia. A bone marrow examination (see Bone Marrow Examination) is almost always done to confirm the diagnosis and to distinguish AML from other types of leukemia.

Prognosis

Without treatment, most people with AML die within a few weeks to months of the diagnosis. With therapy, between 20% and 40% of people survive at least 5 years, without any relapse. Because relapses almost always occur within the first 5 years after initial treatment, most people who remain leukemia-free after 5 years are considered cured. People who have the poorest prognosis are those older than 60, those who have certain subtypes of AML, those who develop AML after undergoing chemotherapy or radiation therapy for other cancers, and those whose leukemia evolved slowly after a period of months to years of abnormal blood counts.

Acute promyelocytic leukemia was once considered the most malignant form of leukemia. Now, it is one of the most curable forms of AML. More than 70% of people with acute promyelocytic leukemia can be cured. Rapid diagnosis is essential.

Treatment

Treatment is aimed at bringing about prompt remission—the destruction of the vast majority of leukemia cells. AML responds to fewer drugs than does acute lymphocytic leukemia. In addition, treatment often makes people sicker before they get better.Treatment suppresses bone marrow activity, resulting in very few white blood cells, particularly neutrophils. Having too few neutrophils makes infection likely. Treatment also disrupts the mucosae (such as the lining of the mouth), which makes it easier for bacteria to enter the body. Meticulous care is taken to prevent infections, and any that occur must be promptly treated. Red blood cell and platelet transfusions are invariably also needed.

Induction chemotherapy is the first phase of treatment. Chemotherapy drugs generally include cytarabine for 7 days given by a continuous infusion or as a single larger dose and daunorubicin (or idarubicin or mitoxantrone) given intravenously for 3 days. Other drugs that may be given include 6-thioguanine and etoposide.

Consolidation chemotherapy is given once AML is in remission. People usually receive several courses of additional chemotherapy beginning a few weeks after the initial treatment to help ensure that as many leukemia cells as possible are destroyed. Unlike in acute lymphocytic leukemia, preventive treatment to the brain usually is not needed for adults, and long-term lower-dose chemotherapy (maintenance therapy) has not been shown to improve survival.

People with acute promyelocytic leukemia can be treated with a type of vitamin A called all- trans -retinoic acid (tretinoin). Chemotherapy is frequently combined with the all- trans -retinoic acid, especially if the person initally has a high white blood cell count. Arsenic chemical compounds are also uniquely effective in this subtype of AML.

Relapse

People who have not responded to treatment and younger people who are in remission but who are likely to have a high rate of relapse (generally identified by certain chromosomal abnormalities) may be given high doses of chemotherapy drugs followed by stem cell transplantation (see Stem Cell Transplantation).

When relapse occurs, additional chemotherapy for people unable to undergo stem cell transplantation is less effective and often poorly tolerated. Another course of chemotherapy is most effective in younger people and in people whose initial remission lasted longer than 1 year. Doctors take many factors into consideration when determining the advisability of additional intensive chemotherapy for people with AML in relapse. A newer drug, gemtuzumab ozogamicin, which combines an antibody with a chemotherapy drug as an attempt to specifically "target" the leukemia cells, is effective in certain people after relapse has occurred. Further testing of the drug is ongoing.


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