Acute myeloid leukemia

Synonyms

2

Overview

Acute myeloid leukemia (AML) is a cancer that affects the blood and bone marrow. Conditions are generally called "acute" when they develop quickly and have an aggressive course. The signs and symptoms of AML vary but may include easy bruising; bone pain or tenderness; fatigue; fever; frequent nosebleeds; bleeding from the gums; shortness of breath; and/or weightloss. AML is one of the most common types of leukemia among adults and is rarely diagnosed in people under age 40. There are many potential causes of AML such as certain blood disorders, inherited syndromes, environmental exposures, and drug exposures; however, most people who develop AML have no identifiable risk factor. Treatment may include a combination of chemotherapy, radiation therapy, bone marrow transplant and/or other drug therapy.

Symptoms

General signs and symptoms of the early stages of acute myelogenous leukemia may mimic those of the flu or other common diseases. Signs and symptoms may vary based on the type of blood cell affected.  Signs and symptoms of acute myelogenous leukemia include:

  • Fever
  • Bone pain
  • Lethargy and fatigue
  • Shortness of breath
  • Pale skin
  • Frequent infections
  • Easy bruising
  • Unusual bleeding, such as frequent nosebleeds and bleeding from the gums

Causes

There are many potential causes of AML such as certain blood disorders, inherited syndromes, chemical exposures, ionizing radiation, environmental exposures, and drug exposures; however, most people who develop AML have no identifiable risk factor.

Preleukemia:

"Preleukemic" blood disorders, such as myelodysplastic syndrome or myeloproliferative disease, can evolve into AML; the exact risk depends on the type of MDS/MPS.

Chemical exposure:

Exposure to anticancer chemotherapy, in particular alkylating agents, can increase the risk of subsequently developing AML. The risk is highest about three to five years after chemotherapy. Other chemotherapy agents, specifically epipodophyllotoxins and anthracyclines, have also been associated with treatment-related leukemia. These treatment-related leukemias are often associated with specific chromosomal abnormalities in the leukemic cells.

Occupational chemical exposure to benzene and other aromatic organic solvents is controversial as a cause of AML. Benzene and many of its derivatives are known to becarcinogenic in vitro. While some studies have suggested a link between occupational exposure to benzene and increased risk of AML, others have suggested the attributable risk, if any, is slight.

Radiation:

High amounts of ionizing radiation exposure can increase the risk of AML. Survivors of the atomic bombings of Hiroshima and Nagasaki had an increased rate of AML, as did radiologists exposed to high levels of X-rays prior to the adoption of modern radiation safety practices.

Genetics:

A hereditary risk for AML appears to exist. Multiple cases of AML developing in a family at a rate higher than predicted by chance alone have been reported. Several congenital conditions may increase the risk of leukemia; the most common is probably Down syndrome, which is associated with a 10- to 18-fold increase in the risk of AML

Prevention

It's not known what causes most cases of acute myeloid leukemia (AML). Since most leukemia patients have no known risk factors, at the present time there is no way to prevent it from developing.

Factors that may increase your risk of acute myelogenous leukemia include:

  • Increasing age. The risk of acute myelogenous leukemia increases with age. Acute myelogenous leukemia is most common in adults age 65 and older.
  • Your sex. Men are more likely to develop acute myelogenous leukemia than are women.
  • Previous cancer treatment. People who've had certain types of chemotherapy and radiation therapy may have a greater risk of developing AML.
  • Exposure to radiation. People exposed to very high levels of radiation, such as survivors of a nuclear reactor accident, have an increased risk of developing AML.
  • Dangerous chemical exposure. Exposure to certain chemicals, such as benzene, is linked to greater risk of AML.
  • Smoking. AML is linked to cigarette smoke, which contains benzene and other known cancer-causing chemicals.
  • Other blood disorders. People who've had another blood disorder, such as myelodysplasia, polycythemia vera or thrombocythemia, are at greater risk of developing AML.
  • Genetic disorders. Certain genetic disorders, such as Down syndrome, are associated with an increased risk of AML.

Diagnosis

The first clue to a diagnosis of AML is typically an abnormal result on a complete blood count. While an excess of abnormal white blood cells (leukocytosis) is a common finding, and leukemic blasts are sometimes seen, AML can also present with isolated decreases in platelets, red blood cells, or even with a low white blood cell count (leukopenia). While a presumptive diagnosis of AML can be made via examination of the peripheral blood smear when there are circulating leukemic blasts, a definitive diagnosis usually requires an adequate bone marrow aspiration and biopsy.

Marrow or blood is examined via light microscopy, as well as flow cytometry, to diagnose the presence of leukemia, to differentiate AML from other types of leukemia (e.g. acute lymphoblastic leukemia - ALL), and to classify the subtype of disease (see below). A sample of marrow or blood is typically also tested for chromosomal abnormalities by routine cytogenetics or fluorescent in situ hybridization. Genetic studies may also be performed to look for specific mutations in genes such as FLT3, nucleophosmin, and KIT, which may influence the outcome of the disease.

Cytochemical stains on blood and bone marrow smears are helpful in the distinction of AML from ALL, and in subclassification of AML. The combination of a myeloperoxidase or Sudan black stain and a nonspecific esterase stain will provide the desired information in most cases. The myeloperoxidase or Sudan black reactions are most useful in establishing the identity of AML and distinguishing it from ALL. The nonspecific esterase stain is used to identify a monocytic component in AMLs and to distinguish a poorly differentiated monoblastic leukemia from ALL.

The diagnosis and classification of AML can be challenging, and should be performed by a qualified hematopathologist or hematologist. In straightforward cases, the presence of certain morphologic features (such as Auer rods) or specific flow cytometry results can distinguish AML from other leukemias; however, in the absence of such features, diagnosis may be more difficult.

According to the widely used WHO (World Health Organization) criteria, the diagnosis of AML is established by demonstrating involvement of more than 20% of the blood and/or bone marrow by leukemic myeloblasts. The French–American–British (FAB) classification is a bit more stringent, requiring a blast percentage of at least 30% in bone marrow (BM) or peripheral blood (PB) for the diagnosis of AML. AML must be carefully differentiated from "preleukemic" conditions such as myelodysplastic or myeloproliferative syndromes, which are treated differently.

Because acute promyelocytic leukemia (APL) has the highest curability and requires a unique form of treatment, it is important to quickly establish or exclude the diagnosis of this subtype of leukemia. Fluorescent in situ hybridization performed on blood or bone marrow is often used for this purpose, as it readily identifies the chromosomal translocation [t(15;17)(q22;q12);] that characterizes APL. There is also a need to molecularly detect the presence of PML/RARA fusion protein, which is an oncogenic product of that translocation

Prognosis

Acute means that the leukemia can progress quickly, and if not treated, would probably be fatal in a few months.

Treatment

Treatment of acute myelogenous leukemia depends on several factors, including the subtype of the disease, your age, your overall health and your preferences.

In general, treatment falls into two phases:

  • Remission induction therapy. The purpose of the first phase of treatment is to kill the leukemia cells in your blood and bone marrow. However, remission induction usually doesn't wipe out all of the leukemia cells, so you need further treatment to prevent the disease from returning.
  • Consolidation therapy. Also called post-remission therapy, maintenance therapy or intensification, this phase of treatment is aimed at destroying the remaining leukemia cells. It's considered crucial to decreasing the risk of relapse.

Therapies used in these phases include:

  • Chemotherapy. Chemotherapy is the major form of remission induction therapy, though it can also be used for consolidation therapy. Chemotherapy uses chemicals to kill cancer cells in your body.

    People with AML generally stay in the hospital during chemotherapy treatments because the drugs destroy many normal blood cells in the process of killing leukemia cells. If the first cycle of chemotherapy doesn't cause remission, it can be repeated.

  • Other drug therapy. Arsenic trioxide (Trisenox) and all-trans retinoic acid (ATRA) are anti-cancer drugs that can be used alone or in combination with chemotherapy for remission induction of a certain subtype of AML called promyelocytic leukemia. These drugs cause leukemia cells with a specific gene mutation to mature and die, or to stop dividing.
  • Stem cell transplant. A stem cell transplant, also called a bone marrow transplant, may be used for consolidation therapy. A stem cell transplant helps re-establish healthy stem cells by replacing unhealthy bone marrow with leukemia-free stem cells that will regenerate healthy bone marrow.
  • Gemtuzumab ozogamicin (Gilotarb) _ FDA approved for the Treatment of patients with CD33 positive acute myeloid leukemia in first relapse who are 60 years of age or older and who are not considered candidates for cytotoxic chemotherapy

Prior to a stem cell transplant, you receive very high doses of chemotherapy or radiation therapy to destroy your leukemia-producing bone marrow. Then you receive infusions of stem cells from a compatible donor (allogeneic transplant).

You can also receive your own stem cells (autologous transplant) if you were previously in remission and had your healthy stem cells removed and stored for a future transplant.

  • Clinical trials. Some people with leukemia choose to enroll in clinical trials to try experimental treatments or new combinations of known therapies

Resources

Refer to Research Publications.