Acute myelocytic leukemia (AML)

ALSO KNOWN AS: Acute myeloid leukemia, acute myelogenous leukemia, acute myeloblastic leukemia, acute myelomonocytic leukemia, granulocytic leukemia, acute nonlymphocytic leukemia, acute promyelocytic leukemia

RELATED CONDITIONS: Acute lymphoblastic leukemia, myelodysplastic syndrome

DEFINITION: Acute myelocytic leukemia (AML) describes a malignant proliferation in the bone marrow of an undifferentiated blood-forming cell of the myeloid line. AML begins with the genetic alteration of a single cell. That cell, called a blast cell, is the foundation from which the leukemia follows. The process of normal blood cell formation, or hematopoiesis, begins with undifferentiated cells, known as stem cells, inside the bone marrow. Stem cells differentiate into blasts, and these primitive blast cells give rise to red blood cells, platelets, and white blood cells. It is the accumulation of blast cells in the bone marrow and their failure to differentiate that has lethal consequences within just a few weeks or months if unchecked. Although the rate of cure has improved, treatment is still associated with high morbidity and mortality.

Risk factors: Certain genetic disorders have an associated AML risk, including Down syndrome, Fanconi anemia, and Shwachman-Diamond syndrome. Other risk factors include some forms of chemotherapy, radiation therapy, and exposure to tobacco smoke and benzene.

Etiology and the disease process: The process leading to acute myelocytic leukemia involves the interruption in the progression of an undifferentiated progenitor cell in the bone marrow that normally matures into red blood cells, white blood cells (neutrophils, eosinophils, basophils, and monocytes), and megakaryocytes. Megakaryocytes are bone marrow cells responsible for the production of the blood platelets necessary for blood clotting. Bone marrow is the soft interior of some bones, such as the skull, shoulder blades, ribs, pelvis, and backbones. It comes in two varieties: red marrow and yellow marrow. The red marrow, also called myeloid tissue, is the source of AML activity. Red blood cells, platelets, and most white blood cells arise from a parent cell in the red marrow. Many references limit the discussion of AML to only the direct descendants of the myeloid line; these are the neutrophils, eosinophils, and basophils.

When blast cells do not mature properly, they accumulate in the bone marrow. It is the proliferation and the accumulation of this hemopoietic cell in the bone marrow that defines AML. Although research has not completely unraveled the process of this leukemic transformation, there is strong evidence of underlying chromosomal damage. For example, a variety of mutations are associated with AML, with damage to the gene for FMS-related tyrosine kinase 3 (FLT3) being the most prominent. Normally, the receptor encoded by FLT3 signals undifferentiated blast cells in the bone marrow to proliferate when there is a need for additional circulating blood cells. The signal stops when the supply is sufficient, but in AML, the switch stays on, and unconstrained blast cell proliferation follows. Although AML begins with defective bone marrow cells, it generally moves quickly into the peripheral blood and may spread to other parts of the body, such as the liver, spleen, testes, brain, spinal cord, and lymph nodes.

Incidence: According to the National Cancer Institute, there were about 20,240 new cases of AML in 2023. Overall, the 2021 incidence rate of AML among the general American population is 4.3 per 100,000. Because AML is associated with accumulating genetic defects, the incidence increases with age. In 2021, the AML incidence for those under 15 years of age was 0.7 per 100,000 persons. For those 50-64, the incidence jumped to 5.0. For the ages 65-74, the rate was 14.0. For the population greater than 75, the incidence rate was 27.3. The median age at diagnosis was 68 years old. The median age at death was 74.  

Symptoms: Clinical findings reflect the replacement of normal bone marrow elements with malignant blast cells. Probably the most consistent early complaints in AML are a history of increasing lethargy later followed by skin, soft-tissue, or respiratory infection. Some patients will have small red or purple spots on the body, called petichia, resulting from broken blood vessels. Liver, spleen, and lymph node enlargement is common, as is weight loss. Some symptoms are nonspecific but quite common in AML patients. These include swollen gums; pale skin; black-and-blue marks; achiness in the knees, hips, or shoulder; mild fever; shortness of breath during even light exertion; and the slow healing of cuts.

Screening and diagnosis: The diagnostician must distinguish AML from other myeloproliferative disorders, chronic myelogenous leukemia, and myelodysplastic syndromes. Although many supporting tests and symptoms point toward a diagnosis, the definitive finding of AML will require bone marrow aspirate and biopsy. Short of examination, other indicators will raise suspicion. About one-third of AML patients will have an enlarged spleen and high levels of uric acid in the blood. The peripheral white blood cell count is not a good indicator, as it may be increased, decreased, or normal. However, there usually will be reduced numbers of granulocytes (neutrophils, basophils, and eosinophils) and platelets in the blood. Blast cells in the peripheral blood appear in only 15 percent of AML patients initially, but this number rises to half of those patients with decreased number of circulating white blood cells (leukopenia).

There is no standard staging system for AML. Generally, doctors describe the status of the condition as untreated, in remission, or recurrent. However, bone marrow examination more closely defines AML as belonging to one of eight cell subtypes. Doctors tailor the treatment to the subtype. The subtypes are as follows:

• • M0: Myeloblastic, on special analysis
• • M1: Myeloblastic, without maturation
• • M2: Myeloblastic, with maturation
• • M3: Promyeloctic
• • M4: Myelomonocytic
• • M5: Monocytic
• • M6: Erythroleukemic
• • M7: Megakaryocytic

Treatment and therapy: The goal of AML treatment is the destruction of the leukemic cells. However, this requires the suppression of bone marrow activity, which brings unfortunate side effects. With the bone marrow suppressed, fewer white cells are available to fight infection and fewer red cells and platelets are present to maintain a healthy oxygen exchange and clot formation. This almost always requires treatment with antibiotics and blood transfusions.

Initial treatment or induction therapy begins with a hospital stay of about a week using chemotherapy in a combination of drug types. Generally, induction therapy requires more than one round of treatment, as it is likely that some AML cells will survive. Even if the induction therapy seems successful, the doctors assume that leukemic cells still exist though unrevealed on biopsy examination. In the unusual event that leukemia has spread to the brain or spinal cord, chemotherapy is also introduced into the cerebrospinal fluid.

At a later date, a follow-up round of less intensive treatments called consolidation therapy brings the patient back to the hospital to maintain remission status. Remission describes a normal peripheral blood profile, a normal bone marrow free of excess blasts, and a normal clinical status. Doctors generally reserve stem cell transplantation with more vigorous chemotherapy for those patients susceptible to relapse, although it is sometimes part of the consolidation regimen. However, there is some debate among doctors as to the risks and benefits of this treatment. For relapsed patients who are unable to undergo the rigors of stem cell transplantation, additional chemotherapy is generally not well tolerated or effective.

Doctors adapt specific chemotherapies to the subtype of the leukemia. Usually, this will be some combination of an anthracycline class agent with cytabrine. In some cases, a third drug, 6-thioguanine, is added. Also factored into the treatment strategy are the patient’s age, clinical status, and leukemia profile. Although quite variable, hospital stays for induction and consolidation therapies may require weeks or even months. Typically, chemotherapy will drive the patient’s blood cell counts down to dangerously low levels. This will require drugs to elevate white blood cell counts as well as antibiotics and blood transfusions to protect against complications.

Prognosis, prevention, and outcomes: The prognosis of patients with AML largely depends on the patient’s age. In part, this is due to chemoresistance or the biological response of cells to survive the toxic stress of chemotherapy. Because chemoresistance tends to increase with age, important therapies are less effective in older patients. Also, the difference in the mechanisms of chromosome translocations in the young and older patients allows for a more favorable outcome in the younger patient.

According to the American Cancer Society, 2023 data indicated about 90 percent of adults with AML will reach complete remission status. Almost 30 percent of adults diagnosed with AML will survive three or more years following diagnosis if given aggressive treatment—this constitutes about 67 percent of those who achieve complete remission. For children, the five-year survival rate was 65-70 percent.

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Other Resources

The Leukemia and Lymphoma Society

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