Leukemia & Lymphoma Society - Acute Myeloid Leukemia

About 12,810 Americans were expected to be diagnosed with acute myelogenous leukemia (AML) last year. The chance of getting AML increases with age. However, children and adults of any age can develop AML. About one in five children with leukemia has AML. The goal of treatment for AML is to bring about a remission or to cure the disease.

The number of patients with AML who enter remission, stay in remission for years or are cured has increased significantly over the past 30 years.

Causes and Risk Factors

AML starts with a change to a single cell in the bone marrow. With AML, the leukemic cells are often referred to as blast cells.

Medical researchers are working to understand the cell changes that lead to AML.

Down syndrome and other uncommon genetic disorders such as Fanconi anemia and Shwachman-Diamond syndrome and others are associated with an increased risk of AML.

Most people who have these risk factors do not get AML - and most people with AML do not have these risk factors.

You cannot catch AML from someone else. Very rarely, more cases of AML than would be expected are diagnosed within the same family. It is thought that children in these families inherit a gene that makes them more susceptible to developing AML. Research to improve the understanding of familial cancers and effective medical management of them is underway.

Signs and Symptoms

Some of the signs and symptoms for AML are common to many illnesses. Some changes that a person with AML may have are:

The best advice for any person troubled by any of these symptoms is to see a healthcare provider.

Diagnosis

Blood and Bone Marrow Tests

Blood and bone marrow tests are done to diagnose AML. A bone marrow aspiration and a bone marrow biopsy are two of the tests that are done. A bone marrow aspiration shows the cell-type and certain abnormalities by looking at proteins on the cell's surface. It can be used for cytogenetic analysis and other tests.

Cytogenetic analysis is a lab test to examine the chromosomes of the leukemic blast cells. Some changes to chromosomes give doctors

information about how to treat their AML patients.

A bone marrow biopsy shows chromosome and gene abnormalities and how much disease is in the marrow. Both tests are also done to see if treatment is destroying leukemic blast cells. The doctor uses information from these tests to decide if leukemia is present, the type of treatment the patient needs and the best treatment for the patient.

The doctor will also consider the patient's age, the general health of the patient, and the presence of certain changes to chromosomes to determine the best treatment for the patient.

Subtypes of AML

There are different types of AML. These are called subtypes. Most patients diagnosed with AML have one of eight different subtypes:

Designation	Cell Subtype
M0	Myeloblastic, on special analysis
M1	Myeloblastic, without maturation
M2	Myeloblastic, with maturation
M3	Promyeloctic
M4	Myelomonocytic
M5	Monocytic
M6	Erythroleukemia
M7	Megakaryocytic

Doctors look at the AML cells in a patient's marrow or blood to identify the patient's subtype of AML. Treatment for AML may vary by subtype. For example, acute promyelocytic leukemia (APL) and acute monocytic leukemia are subtypes of AML that need different treatment than other subtypes of AML.

Treatment

Patients with AML need to start chemotherapy right away. It is important to get medical care in a center where doctors are experienced in treating AML patients.

There are two parts of AML treatment, called induction therapy and consolidation therapy. The aim of induction therapy is to kill as many AML cells as possible and get blood cell counts back to normal over time. When the aim of induction therapy is achieved it is called a remission. A patient in remission feels better over time and leukemia cells can't be seen in his or her blood or marrow.

Induction therapy is done in the hospital. Patients are often in the hospital for three to four weeks. Some patients may need to be in the hospital longer.

Many different drugs are used to kill leukemic cells. Each drug type works in a different way to kill the cells. Combining drug types can strengthen the effects of the drugs. New drug combinations are being studied. Two or more chemotherapies are usually used together to treat AML. Some drugs are given by mouth. Most chemotherapies are given through a catheter placed into a vein, usually in the patient's upper chest.

The first round of chemotherapy usually does not get rid of all the AML cells. Most patients will need more treatment. Usually the same drugs are used for more rounds of treatment to complete induction therapy.

More treatment is usually needed even after a patient with AML is in remission. This second part of treatment is called consolidation therapy. It is needed because some AML cells remain that are not found by common blood or marrow tests. Consolidation therapy is also done in the hospital. As with induction therarpy, patients may be in the hospital for three to four weeks, or sometimes longer. Consolidation therapy may include chemotherapy with or without an allogeneic stem cell transplant or autologous stem cell transplant.

Follow-Up Visits
Patients who are in remission still need to see the doctor regularly for exams and blood tests. Bone marrow tests may be needed too. The doctor may recommend longer waits between follow-up visits if a patient continues to be disease-free.

Refractory Leukemia and Relapsed Leukemia
Some patients still have AML cells in their marrow after treatment. This is called refractory AML. With refractory AML, drugs that were not used to treat the patient's AML in the first part of treatment may be given. Allogeneic stem cell transplantation also may be used for certain patients.

For patients who relapse, the same or different drugs may be given, or stem cell transplantation may be used.

Treatment in Children

There are about 4,220 new cases of childhood leukemia expected to be diagnosed in 2008 in the United States (for children 0-19 years of age). Induction therapy for children with AML starts with two or three drugs. Stronger treatment is needed after a child with AML is in remission. This is called intensive consolidation therapy. It is given because usually some AML cells remain after induction therapy. These AML cells do not show up in standard blood or marrow tests. Consolidation therapy in children includes a number of chemotherapies.

About four out of five children with AML go into remission. About half of children with AML have no signs of disease after five years. Most of these children are considered cured.

Allogeneic stem cell transplants may be used in children who are not doing well or who relapse after high-dose chemotherapy. Doctors will discuss the benefits and risks with parents and older children.

Long-Term and Late Effects of Treatment for Children
Transplant and other treatment can cause long-term or late effects involving a child's growth, hormones, heart and other parts of the body. Treatment for leukemia can also cause problems with learning skills. But special education methods can help these children learn. It is important to identify problems early. Talk to the doctor about when your child's learning skills should be assessed.

Treatment in Older Adults

At least half of patients are over 65 years old when their disease is diagnosed. Some healthy older patients can be treated with the same doses of chemotherapy as younger adults. Sometimes older patients have other medical problems, such as heart disease, kidney or lung disease, or diabetes. The doctor takes these other medical conditions into account to decide which drugs and dosages to use. The doctor will also consider the patient's type of AML, his or her physical ability to handle the treatment and feelings about the treatment approach.

Treating Special AML Subtypes

Acute Promyelocytic Leukemia Treatment
Acute promyelocytic leukemia is the most curable form of AML. People with acute promyelocytic leukemia are treated with a substance that comes from vitamin A called all-trans retinoic acid (ATRA). This treatment is given along with chemotherapy. It is often successful in bringing this type of leukemia into remission. Another treatment for acute promyelocytic leukemia is arsenic trioxide (ATO). It may be given to patients whose leukemia has returned or cannot be brought under control with chemotherapy and ATRA.

Acute Monocytic Leukemia Treatment
In one type of AML, called acute monocytic leukemia, the leukemia cells are more likely to invade the lining of the spinal canal or brain. The patient gets chemotherapy directly into the spinal canal to treat these hard-to-reach cells. A needle is placed into the spinal canal during a procedure called a spinal tap. Spinal fluid is removed and chemotherapy is injected into the spinal canal. Sometimes radiation therapy may be used to treat a large mass of leukemia cells in the spine or brain.

Allogeneic Stem Cell Transplantation

Chemotherapy used to treat AML also kills the healthy stem cells in the marrow. Allogeneic stem cell transplant is used to treat some AML patients.

When the donor cells attack the AML cells it is called graft versus leukemia or GVL. GVL is also called graft versus cancer.

Allogeneic stem cell transplant can be a high-risk procedure. For this reason, it may not be a good treatment for some AML patients. The decision to do a transplant depends on the patient's age and overall health, the chances that chemotherapy alone will cure his or her AML, and the patient's understanding of the benefits and risks of the transplant. Doctors will discuss these with patients and parents of young children with AML.

AML patients who have an allogeneic stem cell transplant are usually between the ages of 1 and 50 and are in remission. In addition, the patient needs to have a matched donor.

Doctors are studying a type of stem cell transplant called a nonmyeloablative stem cell transplant. This treatment may be helpful for older patients.

Autologous Stem Cell Transplantation

Patients who do not have a matched donor for a stem cell transplant may be given very high doses of chemotherapy and an autologous stem cell transplant instead. The goal of an autologous stem cell transplant is to restore the body's ability to make normal blood cells after high-dose chemotherapy.

Disease and Treatment Side Effects

However, chemotherapy and radiation therapy often affect a person's blood counts. The number of red cells may decrease (called anemia). Transfusions of red cells (blood cells that are donated and given to the patient) are usually needed to increase the red cell count. Patients usually have a drop in the number of platelets. If a patient's platelet count is very low he or she usually needs a platelet transfusion to prevent or treat bleeding. A long-lasting and big drop in white cells may lead to an infection. Such infections are usually treated with antibiotics, until the normal white cell count goes up and the infection clears up. Patients with an infection may also have coughing, sore throat, pain when urinating, or frequent loose bowel movements. Or, fever or chills may be the only signs of infection.

To lower the risk of bacterial, viral and fungal infections, patients, visitors and medical staff need to wash their hands well. Also, the patient's central line must be kept clean and patients should follow all medical advice for taking care of their teeth and gums.

Complete blood counts are usually done throughout treatment. If the red cell counts or platelet counts are too low transfusions may be necessary. Growth factors are sometimes given to increase the number of white cells if they are too low. G-CSF (Neupogen® or Neulasta®) and GM-CSF (Leukine®) are drugs that increase white cell counts. Your doctor may talk about neutropenia (a lower than normal neutrophil count) and absolute neutrophil count or ANC, which is the number of white cells that are neutrophils.

Other side effects of treatment include: mouth sores, rashes, dry mouth, diarrhea, nausea, constipation, hair loss, vomiting, or changes in the way certain foods taste. Drugs or other therapies may be helpful to prevent or treat nausea, vomiting and other side effects.

Chemotherapy may cause the amount of uric acid to increase in the blood of some AML patients. (Some patients also have a buildup of uric acid from the disease itself.) Uric acid is a chemical made in the body. A high level of uric acid can cause kidney stones. Patients with high uric acid levels may be given a drug called allopurinol (Aloprim®, Zyloprim®) by mouth. Another drug used to treat high uric acid levels is called rasburicase(Elitek®), which is given by vein.

Clinical Trials

Clinical trials are used to study new drugs, new treatments or new uses for approved drugs or treatments. Research has contributed to the growing number of patients with AML who enter remission, stay in remission for years or are cured. One of the challenges for future research is to develop treatments that help more patients.

Scientists are trying to create new drugs or find them from natural sources. They are also studying new combinations of drugs already being used. Scientists are studying ways to boost the body's natural defenses, called immunotherapy. The goal is to kill or prevent the growth of AML cells.

Scientists are studying cytokines, natural substances made by cells. Cytokines can also be made in the lab. They can be used to help restore normal blood cell counts during treatment or boost the immune system to better attack the leukemia cells.

Leukemia-specific therapy, based on a patient's specific subtype of leukemia, such as the type of chromosome changes, is being studied.

The AML cells of some patients are not as easily killed by drugs as those of other patients. This is called drug resistance. Scientists are trying to understand why some AML cells are resistant to the effects of chemotherapy. This will help them develop better treatments.

Scientists are studying the exact genetic changes that cause a normal cell to become an AML cell. This research is leading to the development of new treatments. These treatments could block the effects of cancer-causing genes (called oncogenes).

• Farnesyl transferase inhibitors, for example tipifarnib (Zarnestra®) or lonafarnib
• FLT-3 inhibitors
• Proteasome inhibitors, such as bortezomib (Velcade®)
• Multi-drug Resistance Modulators, such as cyclosporine A or PSC-833
• Antisense molecules (Genasense®, GTI-2040)
• Hypomethylating agents, such as decitabine (Dacogen®)
• Histone deacetylase inhibitors, such as depsipeptide.

Talk to the Doctor

It may be helpful to write down questions to ask your doctor. Then you can write down your doctor's answers and review them later. You may want to bring a family member or friend with you to the doctor. This person can listen, take notes and offer support. Some patients record information and listen to it at home.

Get More Information

The Leukemia & Lymphoma Society (LLS) offers ongoing education programs featuring leading leukemia specialists discussing the latest issues in the diagnosis and treatment of leukemia. Visit the Leukemia Education Series page to find out about upcoming and archived programs. These programs are offered at no charge.

Further details of treatment and supportive care and the beneficial and adverse effects of treatment may be obtained from LLS's informational booklet on acute myelogenous leukemia. Read or order online LLS's free publication Acute Myeloid Leukemia.

Understanding AML