Acute Myelogenous Leukemia (AML) Information
Many people with leukemia want to take an active part in making decisions about their medical care. One of the most important things you can do is to learn as much as possible about your diagnosis and course of treatment. This will help you make informed decisions about your care and prepare you to overcome some of the physical and emotional challenges you may face.
The information provided here has been created to help you learn more about leukemia — a type of cancer that begins in the blood-forming cells of the bone marrow. Along with an overview of the most common types of leukemia, you will find a detailed discussion of acute myelogenous leukemia (AML), how AML is diagnosed and treated, as well as the role LEUKINE® (sargramostim) may play in helping the immune system recover following induction chemotherapy in AML in older patients.
- What is leukemia?
- Types of leukemia
- AML overview and insights
- What causes AML?
- What are the signs and symptoms of AML?
- Diagnosing AML
- Expectations for recovery
- How is AML treated?
- AML treatment and the risk of infection
- Treatments to help boost the immune system and fight infection
What is leukemia?
Leukemia is a cancer of the cells of the blood and blood-forming tissue such as bone marrow. In patients with leukemia, some blood-forming — or hematopoietic — cells of the bone marrow are damaged and remain in an abnormal or immature form. As a result, these cells are unable to function properly. Over time, these leukemic cells multiply and crowd out the normal cells of the bone marrow, which makes it hard for the blood to do its work. For example, normal-functioning red blood cells called erythrocytes carry oxygen in the body. When the number of red blood cells is reduced, anemia occurs, which can leave you feeling run down, tired, or short of breath.
Platelets, which are fragments of larger cells also found in your bone marrow, may also be affected. Platelets are necessary for normal blood clotting and clump together to prevent bleeding. A low level of platelets, known as thrombocytopenia, can lead to bruising and bleeding, especially in the skin, nose, and gums. Under normal circumstances the hematopoietic cells of the bone marrow make white blood cells (WBCs), or leukocytes, to fight infection caused by bacteria, viruses, and fungi. Very low levels of these WBCs, a condition known as neutropenia, can increase the risk of infection.
Leukemia literally means "white blood" in Greek and occurs when there is an excess of abnormal or immature WBCs. In some patients, these cells are so plentiful that the blood actually develops a whitish tinge. If left untreated, leukemia can cause bone marrow failure. This happens when the surplus leukemic cells overwhelm the bone marrow, enter the bloodstream, and eventually invade other parts of the body, such as the lymph nodes, spleen, and liver.
Types of leukemia
There are several types of leukemia, but the following four are the most common:
- Acute lymphocytic leukemia (ALL)
- Acute myelogenous leukemia (AML)
- Chronic lymphocytic leukemia (CLL)
- Chronic myelogenous leukemia (CML)
Leukemias are grouped by how quickly the disease develops and by the type of WBC that is affected. Acute leukemias usually develop suddenly and worsen quickly. The blood cells are malformed and cannot carry out their normal function. Acute leukemias require immediate and aggressive treatment. On the other hand, chronic leukemias may exist for years before they are diagnosed or need to be treated. Early in the disease, people with chronic leukemia may not have any symptoms. However, chronic leukemias slowly worsen and cause symptoms as the number of leukemic cells in the blood rises.
Leukemias are also classified by the cell lineage that gives rise to the disease. The process of blood formation is known as hematopoiesis and takes place in the bone marrow. Self-renewing cells called stem cells are responsible for making all the blood cells for the body. As these cells multiply, they develop into one of two types of cells: myeloid cells or lymphoid cells. When leukemia develops in the lymphoid cell line, it is called lymphocytic leukemia; when the myeloid cell line is affected, this is known as myelogenous leukemia.
Myelogenous leukemia is the result of an increase in WBCs that are made in the bone marrow. Normal WBCs play an important role in the body's defense against infection. However, leukemic WBCs lack this crucial ability, leaving the body vulnerable to infectious organisms such as bacteria, viruses, and fungi.
AML overview and insights
Acute myelogenous leukemia (AML) is the most common adult acute form of leukemia, affecting approximately 10,500 people a year in the United States. The incidence of AML rises dramatically in people over 55 years of age (median age of onset is 64 years). AML is also more common in white males than in any other population group.
AML is a malignancy (or cancer) of blood-forming tissues of the bone marrow, characterized by an increase in immature WBCs. Normally, the bone marrow makes cells called "blasts" that mature into several different types of blood cells. AML prevents the blasts from properly developing. Found in the blood and bone marrow, these mutated, leukemic blast cells multiply rapidly and crowd out normal blood cells. People with AML become increasingly susceptible to bleeding and infection as the normal blood cells decrease in number and lose their ability to effectively defend the body against microorganisms. The onset of AML is usually quite sudden.
What causes AML?
Although the specific cause of AML is still not known, scientists believe that genetic, environmental, or immunology factors or viruses may be involved. However, please keep in mind that even if a virus is involved, AML is not contagious. There is no evidence to suggest an increased occurrence of the disease among people such as friends, family, and caregivers who have close contact with leukemia patients. It is thought that rare genetic abnormalities may play a role in AML. In some families, people born with chromosome damage, such as Down's syndrome, may carry genes that could increase their chances of developing AML.
Environmental factors such as high-dose radiation and exposure to toxic chemicals including benzene — commonly used in a variety of industrial applications — have been linked to AML. Some researchers believe that the increased incidence of AML in men may be related to occupational exposures.
People with immune-system deficiencies appear to be at greater risk for AML because of their body's inability to resist foreign organisms. There is also evidence that patients previously treated for cancer with certain chemotherapy agents and radiation therapy stand a higher chance of getting secondary leukemia (leukemia that arises after therapy for another type of cancer), most commonly AML. The distinction is important because secondary AML, seen more often in elderly patients, is less responsive to chemotherapy. Newly diagnosed patients not previously treated for cancer have what is called de novo AML and usually experience a more favorable response to chemotherapy than patients with secondary AML.
Some chemotherapy agents linked to secondary leukemias:
- Procarbazine
- Chlorambucil
- Etoposide
- Mechlorethamine
- Teniposide
- Cyclophosphamide
What are the signs and symptoms of AML?
The following are the most common signs and symptoms associated with AML. However, each individual may experience symptoms differently. These may include:
- Easy bruising
- Nonspecific fatigue or weakness
- Fever
- Petechiae (pinpoint-size, purplish-red spots)
- Bleeding gums
- Slow healing or prolonged bleeding of cuts
- Weight loss
Please keep in mind that some people with AML do not notice any symptoms at all. Their AML may be discovered during a blood test or other diagnostic evaluation.
Diagnosing AML
The symptoms of AML sometimes resemble other blood disorders and medical problems. This is why your doctor will conduct a series of diagnostic tests. A suspicion of AML may arise due to an abnormal complete blood count (CBC). The CBC may reveal low levels of platelets or hemoglobin, a protein carried by red blood cells, and an increase in the number of WBCs. It is important to understand that patients with new onset leukemia who have normal or elevated WBC counts may still be at high risk for infection. This can occur because the patient's WBCs are abnormal and thus unable to fight off infections.
If the CBC results look suspicious, the physician will likely request a bone marrow biopsy in which a sample of bone marrow is taken from the hip bone or another large bone. Because it measures the blast count, a biopsy is the only sure way to determine whether leukemia cells are in the bone marrow. This is especially important because AML is defined by greater than 30% blasts in the bone marrow, whereas a normal blast count is less than 5%.
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Chromosome analysis — also known as cytogenetics — of the bone marrow provides valuable information and is used to identify the subtype of AML. For example, a diagnosis of acute promyelocytic leukemia (APL) is subtype M3 and is treated differently than the other AML subtypes.
Your doctor will likely conduct various other tests to assess general health — for example, heart, liver, and kidney function. These assessments are important to ensure that a patient is not particularly prone to side effects from the planned treatment regimen.
Expectations for recovery
The prognosis for recovery from AML varies from patient to patient. Characteristics such as age and general health are key factors as are the features of the disease itself, such as AML subtype. You should know, however, that significant progress has been made in the fight against AML. Though primary causes of concern continue to be chemotherapy-related toxicities and life-threatening infections, many of today's AML patients can anticipate a positive outcome. Current statistics provide reasons for hope. For example, the 5-year survival rate in 1970 was less than 15%. Today, the average is as high as 60% with some AML subtypes. Up to 80% of patients diagnosed with AML can expect a complete remission. This means that there is no evidence of the disease and the patient returns to good health with normal blood and marrow cells. Oncology centers across the country report increasing numbers of patients who are in complete remission at least 5 years after diagnosis of their disease.
How is AML treated?
It is important to understand that AML requires a more aggressive treatment regimen than other types of cancers. AML patients need to be treated right away and will begin their regimen within hours or days of diagnosis. Most patients with AML will receive chemotherapy while in the hospital. Chemotherapy treatments for other types of cancers are often provided on an outpatient basis; however, AML treatment requires extended hospitalization due to the use of strong drugs that severely suppress the immune system. Hospitalization also provides patients with access to a total-care approach, integrating a network of disciplines that include a hematologist/oncologist; nursing, pharmacy, and laboratory services; and other supportive staff. The goals of treatment are to attain a complete remission and, with further treatment, to eradicate the disease and achieve a cure.
Induction chemotherapy
The first phase of treatment that AML patients undergo is called induction chemotherapy. The primary goal of induction chemotherapy is to kill the leukemic blasts that take over the bone marrow and crowd out normal stem cells. This restores the bone marrow to normal function, allowing it to produce healthy cells. Induction chemotherapy involves the use of several drugs in combination (usually cytarabine, daunorubicin, idarubicin, or mitoxantrone) administered over a period of 7 days. While chemotherapy destroys many normal stem cells in the bone marrow, those that do survive now have ample space to resume normal and active development.
Complete remission is defined as less than 5% blasts in the bone marrow and no blasts circulating in the blood. In addition, platelets and normal white cells must show evidence of recovery. Many patients experience a complete remission with this type of treatment regimen.
On day 10, or approximately 4 days after the conclusion of induction chemotherapy, another bone marrow biopsy may be performed. If the blasts are more than 5%, a second course of induction chemotherapy may be given.
Consolidation therapy
Once complete remission is achieved, consolidation therapy is usually given to prevent relapse and to eradicate any residual or remaining leukemic cells from the blood and bone marrow. This is necessary in order to achieve a permanent cure. Without consolidation therapy, complete remission lasts only about 4 to 8 months.
Consolidation therapy consists of further chemotherapy and/or stem cell transplantation (from bone marrow or blood). A stem cell transplant is used to introduce healthy blood-producing cells into the patient's marrow to restore the immune system and allow normal blood cell production.
Treatment for patients who relapse
Although most patients with AML will achieve a remission, some will experience a relapse — a return of the disease. Relapse often occurs because the leukemia cells have become resistant to drug treatment. However, bone marrow transplantation is a treatment option shown to prolong survival in many patients who have experienced a relapse. A bone marrow transplantion may occasionally be recommended as part of the standard consolidation therapy in some subtypes of AML. Bone marrow cells may be obtained from a compatible donor (allogeneic transplant) or cells previously collected from the patient can be used (autologous transplant).
Considerations for elderly patients
As mentioned previously, age is an important factor in determining the success of AML treatment. In patients who are over the age of 60 when diagnosed with AML, it is more difficult to achieve a remission and relapse is more common. One reason is the difficulty of giving full-dose chemotherapy to older patients. Patients in this age group often have other medical problems, such as central nervous system conditions and impaired kidney or liver function. As a result, they may not be able to withstand the required doses of treatment.
AML treatment and the risk of infection
When chemotherapy is used to target and destroy fast-growing cancerous cells, it can also kill healthy cells, including the WBCs that protect your body against infection. WBCs are very important because they are continually on the lookout for signs of infection. When an invading organism does appear, the WBCs have a variety of ways by which they can attack. Below is a list that explains the types and functions of several WBCs.
Patients undergoing chemotherapy frequently experience neutropenia, a condition that occurs when the number of neutrophils is abnormally low. Neutropenia can significantly increase your risk of infection. In fact, 40% of AML patients over the age of 60 experience serious infections following induction chemotherapy.
When functioning normally, here is how several WBCs protect your body against infection.
- Neutrophils are the most abundant type of WBCs, and are the first to rush to the site of an infection and attack foreign antigens
- Monocytes mature into macrophages that act as scavengers to rid your body of worn-out cells and other debris. Macrophages also secrete a wide range of powerful chemicals that work to "activate" other immune system cells
- Dendritic cells are the least abundant, but most potent, type of WBC. They act as observers and messengers who go to the site of infection, collect pertinent information, and "coach" the immune system on how to react to infection
- T cells direct and regulate your body's immune responses or attack cells that are infected or cancerous
- B cells produce antibodies, which are proteins that bind to antigens and mark them for destruction
The high rate of infection is the primary reason your healthcare team will closely monitor your immune system, using blood tests that measure the levels of various cell types. As part of this process, they will monitor your absolute neutrophil count (ANC), an important marker that can indicate your risk of infection. Your ANC refers to the number of neutrophils in your blood. The normal ANC range is 3000-5000 cells per mm3.
Neutrophils are monitored because they are the most abundant type of WBC. Since neutrophils are the first to rush to the site of an infection and attack foreign organisms, neutropenia is an indication that your body may be unable to successfully defend itself against infection. An increased risk of infection occurs once the number of neutrophils drops below 1000 cells per mm3 and especially below 500 cells per mm3. Following chemotherapy, your healthcare team will try to keep your ANC around 1500 cells per mm3 to ensure that your immune system can adequately protect you.1
Absolute Neutrophil Count (ANC)
Monocytes/macrophages and dendritic cells are other important WBCs that play critical roles in preventing infection from bacteria, viruses, and fungi.
Treatments to help boost the immune system and fight infection
Antibiotics are used to treat an infection once it occurs and are sometimes given to prevent infections. In addition, there are other types of drugs available that can help your immune system recover more quickly from chemotherapy, thereby reducing the risk of infection. One of these drugs is LEUKINE® (sargramostim), which is frequently prescribed to help raise your ANC above the critical level of 1500 cells.
LEUKINE is approved for use following induction chemotherapy in older adults with AML, after bone marrow transplantation, before and/or after peripheral blood stem cell transplantation, and for bone marrow transplantation failure or engraftment delay.2 Some doctors may choose to prescribe LEUKINE for other uses as well.
Because LEUKINE increases your body's production of three types of WBCs (neutrophils, monocytes/macrophages, and dendritic cells), it may help activate your body's natural defenses against multiple types of infectious organisms, such as bacteria, viruses, and fungi. If your doctor decides you need an added measure of protection, he or she may prescribe LEUKINE. Click here to learn more about LEUKINE.
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