AML is the second most common type of leukemia in adults with an estimated 12,350 new cases per year. It is slightly more common in men than women and tends to occur in older adults over the age of 50. AML also occurs in children accounting for about 20% of all pediatric leukemias.
The cause of AML is not known, but there are a number of factors that can increase the risk of getting AML. Since AML occurs most frequently in older adults, age is a risk factor. Smoking has also been linked to AML but there are probably other factors that influence that risk.
There are a number of genetic disorders that increase the risk of AML. These include: Down syndrome and several less well known conditions.
People who have other, preexisting blood disorders, especially a condition known as myelodysplastic syndrome, have a much high incidence of AML.
Exposure to high level of radiation and to certain industrial chemicals, such as benzene, also leads to an increased risk of developing AML.
Patients who have received chemotherapy, especially those treated with specific drugs, or radiation therapy for other cancers may develop AML years after their treatment. Despite all of these known risk factors, the majority of patients with AML do not have any known risk factors.
More Information: As more people are treated successfully for cancer, and survive for long periods of time, the incidence of treatment related, second cancers is rising. These second cancers include acute myelocytic leukemia and a premalignant condition known as myelodysplastic syndrome. The rates of treatment related second cancers are highest for people who have been treated for breast cancer, gynecologic cancers and lymphomas.
AML is a disease that develops very quickly and can cause many symptoms. These include fatigue, weakness, bruising or bleeding, especially from the gums, weight loss, fever, swollen lymph nodes, pain, shortness of breath and frequent infections. The buildup of abnormal white blood cells, or blasts, reduces the number of red blood cells, making the person anemic. Blasts don't function like healthy white cells, so people with AML are also much more susceptible to infections. It is very important for people with AML to be treated soon after they become ill. AML progresses rapidly.
Most people with AML are already experiencing multiple symptoms and feeling sick when they see their doctors. The first step is to obtain a complete medical history and do a physical examination. To diagnose any blood disorder, including AML, the doctor will order additional tests. These include:
Blood tests: If a person has AML, those tests will show an usual number of white blood cells, often too many, but sometimes too few. When examined under the microscope, those white blood cells, called blasts, will appear abnormal or very immature in appearance. Special tests called flow cytometry and cytochemistry are then used to distinguish AML from other types of leukemia and to identify the specific subtype of AML.
Molecular testing: In recent years, several specific gene mutations have been found in AML cells. Knowing whether these mutations are present helps to determine the prognosis for patients with AML so this kind of molecular analysis has become more common. Determining the exact type of AML and its genetic characteristics is important in deciding on the best treatment plan and assessing the prognosis.
Bone Marrow biopsy and aspiration: Patients whose blood work indicates that they have AML will also undergo bone marrow biopsy, and possibly a procedure known as a lumbar puncture or spinal tap which allows the pathologist to examine the spinal fluid for the presence of cancer cells, blood or specific substances known as tumor markers.
CT scans and other imaging techniques are not used routinely in diagnosing AML but may be needed to learn more about the cause of symptoms that patients are experiencing. Leukemias are not staged in the same way as many cancers. Instead, they are categorized by their subtype.
As with so many cancers, doctors now understand that AML is not a single disease, that it has several distinct subtypes. Better understanding of the specific genetic and cellular characteristics of a cancer potentially leads to better, more targeted treatments and more accurate prognoses.
More Information: The classification of AML has changed significantly in the last few years and become increasingly complex. The old system was based on the percentage of blasts--or abnormal, immature cells in the blood and bone marrow. The new system looks at a number of factors related to specific genetic, molecular and structural abnormalities. If this sounds complicated, it is. The accurate classification of AML requires a panel of diagnostic studies to analyze all of these factors. Doctors use this information to "stratify risk," that is to determine how aggressive the cancer is and how likely it is to respond to treatment.
One way of classifying AML is by what the cancer cells look like under the microscope. All AML cells are abnormal and immature, but the cancer can arise in different kinds of blood cells. These include:
AML is also categorized by the presence or absence of other genetic mutations. A number of these mutations have been identified in AML. Some are associated with more favorable prognosis and others indicate that the disease will be more difficult to treat successfully. In addition, AML is classified by whether is it is related to other medical conditions or to treatment for a previous cancer. While having this information is important to deciding on treatment and assessing the prognosis, no one can predict the outcomes of treatment for any individual with AML.
The World Health Organization (WHO) has developed a classification system that includes: AML with specific chromosomal abnormalities, also known as recurrent genetic abnormalities
More Information: There are many chromosomal changes that occur in AML, and there are often multiple changes in a single patient. These mutations can be analyzed and grouped together to determine a general prognosis. The chromosomal changes can occur when parts of two chromosomes are exchanged, or translocated, when parts of a chromosome are deleted, or when there are extra copies of a chromosome. Doctors use this highly complex information to classify AML as favorable, intermediate or unfavorable.
Generally, the more favorable changes occur in younger patients, and the less favorable ones in patients over the age of 60. There are many factors that determine how well treatment works, and it is not possible to predict the response for any individual person with AML.
The treatment for any patient with AML depends on a number of factors. These include:
The first treatment for AML is very important. Long term success depends to a large extent on the results of initial treatment. All AML patients should be diagnosed and treated in centers that have the expertise and experience to deliver state of the art therapy and manage any symptoms and side effects.
Chemotherapy is the primary form of treatment for AML. The first goal of treatment is to induce a complete remission, which means to eradicate all of the leukemia cells if possible. Blood counts will return to normal, there will be no leukemia cells visible in the bone marrow and the signs and symptoms of the disease will disappear. This is called induction therapy. For many years, the standard induction therapy for AML has been a combination of two drugs given over a ten day period.
Induction therapy is meant to be a knockout blow to the leukemia and it involves a significant amount of toxicity for the patients. The drugs that kill the cancer cells kill normal cells as well, so patients have a very high risk of infection and bleeding and feel very sick while getting induction therapy. Most patients are hospitalized for three to five weeks during their induction therapy. Approximately 75% of younger patients and 50% of patients over 50 achieve a complete remission. Patients over age 60 frequently cannot tolerate the standard drugs so are given a less toxic combination of drugs and a modified treatment plan.
Doctors know that even if it appears that all the leukemia cells are gone, there is a very high likelihood that they will return without additional treatment. Once a complete remission is achieved, patients receive consolidation therapy, two to six doses of chemotherapy designed to kill any remaining cancer cells. The drugs used for this phase of therapy depend on the patient's age and overall health. The treatment itself is usually given in the hospital but patients often recover at home.
This aggressive approach to treating AML has resulted in real progress. In the 1970s, only 10% of AML patients could expect to survive for five years or more; today the number is approximately 40%.
In some cases, despite treatment, the AML either does not respond (refractory) and the patient does not go into remission, or it comes back after treatment is completed, (recurrent). If the AML comes back after a long remission, it may respond again to the original treatment. If it does not respond to the initial treatment or comes back very quickly, patients can be considered for stem cell transplants or for clinical trials that test new approaches to treating cancer.
Side Effects: The treatments for AML are often aggressive and can cause many side effects. These include hair loss, mouth sores, nausea and vomiting and fatigue. People with AML are also much more likely to develop infections and need to take antibiotics as well as transfusions. Leukemia treatment can also affect fertility. Managing side effects is a very important part of cancer treatment. While it isn't possible to avoid or eliminate these effects, it is possible to treat them or minimize them as much as possible. Patients should talk to their doctors and nurses about what they are experiencing, and be treated in a center that has the expertise to manage these symptoms.
Stem Cell Transplants: Stem cell transplant is a procedure in which doctors use high dose chemotherapy and sometimes radiation therapy to destroy diseased bone marrow, and then replace it with healthy cells, call hematopoietic stem cells. These stem cells have the ability to develop into normal blood and bone marrow cells. Stem cell transplants have replaced the bone marrow transplants for most patients.
For some patients, stem cell transplants are recommended instead of consolidation therapy. These are more often younger patients with less favorable subtypes of AML. Stem cell transplants can also be used to treat recurrent or relapsed AML.
Although APL is considered a subtype of AML, the treatment is very different. APL responds very well to a drug called ATRA, all-trans retinoic acid. This drug, which is similar to vitamin A is combined with chemotherapy and produces complete remissions in a high percentage of patients. Another drug, arsenic trioxide, is also used either in induction or consolidation therapy, or for recurrent APL. Patients with APL are very susceptible to bleeding, so they often receive multiple blood transfusions as part of their treatment.
AML is a very serious disease. It develops quickly and can cause a number of symptoms. The diagnosis and treatment of AML are complicated. There are many subtypes of the disease which influence the prognosis. The treatment for AML is generally aggressive and can result in many side effects. Patients with AML should only be treated in cancer centers that have the expertise and experience to offer the full range of diagnostic, treatment and supportive services to AML patients. There has been progress in treating this disease, but there is still have a long way to go both in terms of increasing the long term remission rates and decreasing the side effects of treatment.