Acute Myelocytic Leukemia
Acute myelocytic (myeloid, myelogenous, myeloblastic, 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.
Acute myelocytic leukemia (AML) is the most common type of leukemia among adults, although it affects people of all ages.
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.
Acute promyelocytic leukemia is a subtype of AML. In this subtype, chromosomal changes in promyelocytes--cells that are at an early stage in the development into mature neutrophils--prevent binding and activity of vitamin A. Without vitamin A activity, normal cell maturation is disrupted, and abnormal promyelocytes accumulate.
Symptoms and Diagnosis
The first symptoms of AML are very similar to those of acute lymphocytic leukemia (see Section 14, Chapter 176). 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 biopsy (see Section 14, Chapter 170) is almost always performed to confirm the diagnosis and to distinguish AML from other types of leukemia.
Prognosis and Treatment
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 develop AML after undergoing chemotherapy and radiation therapy for other cancers, and those whose leukemia evolved slowly after a period of months to years of abnormal blood counts.
Treatment is aimed at bringing about prompt remission--the destruction of all leukemia cells. However, AML responds to fewer drugs than does acute lymphocytic leukemia. In addition, treatment often makes people sicker before they get better, because the treatment suppresses bone marrow activity, resulting in fewer white blood cells, particularly neutrophils. Having too few neutrophils makes infection likely. Meticulous care is taken to prevent infections, and any that occur are promptly treated with antibiotics. Red blood cell and platelet transfusions are invariably also needed.
The first course of drug treatment (induction chemotherapy) generally includes cytarabine for 7 days by a continuous infusion and daunorubicin (or idarubicin or mitoxantrone) for 3 days.
Once AML is in remission, the person usually receives a few courses of additional chemotherapy (consolidation chemotherapy) a few weeks or months after the initial treatment to help ensure that as many leukemia cells as possible are destroyed. A preventive treatment to the brain usually is not needed, and long-term lower-dose chemotherapy (as is used in acute lymphocytic leukemia) has not been shown to improve survival.
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-dose chemotherapy with stem cell transplantation (see Section 16, Chapter 187).
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 more than 1 year. Doctors take many factors into consideration when determining the advisability of additional intensive chemotherapy for people with AML in relapse. A new drug, gemtuzumab ozogamicin, which combines an antibody with a chemotherapy drug as an attempt to specifically "target" the leukemia cells, is effective in some people after relapse has occurred. The long-term benefits of the drug have not been determined.
People with acute promyelocytic leukemia can be treated with a type of vitamin A called all-trans-retinoic acid. Results are best when chemotherapy is used also; currently more than 70% of people with acute promyelocytic leukemia can be cured. Arsenic chemical compounds are also uniquely effective in this subtype of AML.
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