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ACUTE MYELOGENOUS LEUKEMIA

Introduction
Acute myelogenous leukemia (AML) is a cancer of the blood and bone marrow the spongy tissue inside bones where blood cells are made. It's called acute leukemia because it progresses rapidly and affects immature blood cells, rather than mature ones. It's called myelogenous (MI-uh-loj-uh-nus) leukemia because it affects a group of white blood cells called the myeloid cells, which normally develop into the various types of mature blood cells, such as red blood cells, white blood cells and platelets. This type of leukemia is also known as acute myeloid leukemia, acute myeloblastic leukemia, acute granulocytic leukemia and acute nonlymphocytic leukemia. Normally, your bone marrow produces immature cells (stem cells) in a controlled way, and they mature and specialize into the various types of blood cells as needed. In people with acute myelogenous leukemia, the bone marrow produces immature cells that usually develop into a type of abnormal white blood cell. These abnormal cells aren't able to mature and perform their usual functions. Even worse, they multiply rapidly and can crowd out healthy cells, leaving a person with acute myelogenous leukemia vulnerable to infection, anemia or easy bleeding. Leukemia cells can also spread outside the blood to other parts of your body. Acute myelogenous leukemia is the most common form of leukemia. It worsens quickly if not treated, but it initially responds well to treatment. Unfortunately, many people with acute myelogenous leukemia experience a relapse. Much research is focused on decreasing the risk of relapse and improving the long-term outcomes for people with acute myelogenous leukemia.

Signs and symptoms


General signs and symptoms of the early stages of acute myelogenous leukemia may mimic those of the flu or other common diseases. These include:
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Fever Weight loss Bone pain Lethargy and fatigue

More specific signs and symptoms of acute myelogenous leukemia are caused by a lack of properly functioning blood cells, resulting from overcrowding by leukemia cells. A range of problems can occur, depending on the type of blood cell affected:

Red blood cells. These cells carry oxygen from your lungs to all parts of your body. A shortage of red blood cells (anemia) can cause shortness of breath, fatigue and pale skin. White blood cells. These infection fighters help your body ward off germs. A shortage of white blood cells (leukopenia) or of a particular type of white blood cells called neutrophils (neutropenia) can result in frequent infections. Blood platelets. These cells help prevent and control bleeding by prompting your blood to clot. A shortage of blood platelets (thrombocytopenia) can result in easy bleeding and bruising, including frequent or severe nosebleeds, bleeding from your gums, or tiny red marks caused by bleeding into your skin (petechiae).

AML can also cause bleeding gums, abnormal menstrual periods, and enlargement of your spleen or liver. If it involves your lymph nodes, it can cause them to swell. If it spreads outside your blood to your central nervous system or other organs, it can cause headache, weakness, seizures, vomiting, dizziness and blurred vision.

Causes
The cause of acute myelogenous leukemia is damage to the DNA of developing cells in your bone marrow. Under normal circumstances, your DNA is like a set of instructions for your cells, telling them how and when to grow and divide. Certain genes on your DNA called oncogenes promote cell division. Other genes, called tumor suppressor genes, slow down cell division and cause cells to die at the appropriate times.
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Acute myelogenous leukemia can occur when damage to DNA turns on oncogenes or turns off tumor suppressor genes. When this happens, blood cell production goes awry. The bone marrow produces immature cells that develop into leukemic white blood cells called myeloblasts. These abnormal cells are unable to function properly, and they can build up and crowd out healthy cells. The DNA mutations that cause leukemia are usually acquired rather than inherited but researchers and doctors don't always understand exactly how. In some cases, damage to DNA is the result of exposure to cancer-causing chemicals, including previous chemotherapy for other cancers. There's also a chance of AML progressing from other blood diseases and chronic leukemias, such as chronic myelogenous leukemia, myelodysplasia or other disorders in which the bone marrow produces too much of certain types of blood cells (myeloproliferative disorders).

Risk factors
The risk of acute myelogenous leukemia increases with age. It's most prevalent in people in their 60s and older. The disorder is also more common in males than in females. Other possible risk factors include:

Cancer therapy. People who've had certain types of chemotherapy and radiation therapy or treatment for childhood acute lymphocytic leukemia (ALL) may have a greater risk of developing AML. Exposure to radiation and certain chemicals. People exposed to very high levels of radiation, such as survivors of an atomic bomb blast or a nuclear reactor accident, have an increased risk of developing AML. Exposure to certain chemicals, such as benzene which is found in unleaded gasoline and used by the chemical industry also is linked to greater risk of AML. Smoking. AML is linked to cigarette smoke, which contains benzene and other known cancer-causing chemicals. Smokers older than 60 face twice the risk of AML that nonsmokers do. Other blood disorders. People who've had another blood disorder, such as myelodysplasia, polycythemia
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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.

However, many people with AML have no known risk factors whatsoever, and many people who have risk factors never develop cancer.

When to seek medical advice


Acute myelogenous leukemia worsens quickly if not treated. See your doctor if you have any signs or symptoms of AML, so you can act quickly to destroy the cancer before it spreads or causes serious problems.

Screening and diagnosis


CLICK TO ENLARGE Bone marrow test

If you have signs or symptoms of leukemia, you'll need to have your blood and bone marrow cells examined to determine if you have leukemia and, if so, what kind. There are four main types of leukemia and many subtypes. You may undergo the following diagnostic tests:

Blood tests. Most people with acute myelogenous leukemia have too many white blood cells, not enough red blood cells and not enough platelets. The presence of blast cells immature cells usually found in the bone marrow but not normally circulating in the blood is another indicator of acute myelogenous leukemia. Bone marrow test. A blood test can suggest leukemia, but it usually takes a bone marrow test to confirm the diagnosis. If your doctor suspects leukemia, you may be referred to a doctor who specializes in cancer (oncologist) or a doctor who specializes in blood and blood-forming tissues (hematologist). This specialist can use a needle to remove a sample of your bone marrow to
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look for leukemia cells. Usually, the sample is taken from your hipbone (posterior iliac crest). Spinal tap (lumbar puncture). In some cases, it may be necessary to remove some of the fluid around your spinal cord to check for leukemia cells. Your doctor can collect this fluid by inserting a small needle into the spinal canal in your lower back.

A doctor who specializes in diagnosing cancer and other tissue abnormalities typically examines blood, bone and fluid samples under a microscope. He or she can classify blood cells into specific types based on their size, shape and other features. This helps establish the type and subtype of leukemia. If you have AML, you may need further tests to determine the extent of the cancer and classify it into one of the eight subtypes of AML. In AML, the subtypes are based on how mature the cancer cells are at the time of diagnosis and how different they are from normal cells. The subtype is important because it helps dictate the best course of treatment.

Treatment
Treatment of acute myelogenous leukemia depends on your age and the subtype of the disease. 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. A common course of therapy involves two chemotherapy drugs cytarabine
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(Cytosar-U), followed by an anthracycline drug, such as daunorubicin (Cerubidine) or idarubicin (Idamycin). A third medication, thioguanine, is sometimes used. If you have AML, you'll probably stay in the hospital during the treatment cycle because the chemotherapy destroys many normal blood cells in the process of killing leukemia cells. This chemotherapy can cause anemia, infection and bleeding. If the first cycle of treatment doesn't cause remission, you may need it repeated one or two more times. Other drug combinations also may be used, depending on your specific situation. Chemotherapy can also be used for consolidation therapy. This phase may include a combination of different medications that mimic the induction, but usually includes high doses of cytarabine by itself for one to three cycles. Your doctor may also prescribe medications that boost white cell production to reduce the risk of infection. These medications are called granulocyte colony stimulating factors (Neupogen, Leukine).

Other drug therapy. Arsenic trioxide 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. Biological therapy. Also known as immunotherapy, biological therapy uses substances that bolster your immune system's response to cancer. Monoclonal antibodies are one form of biological therapy. These antibodies are produced in a laboratory, but they mimic protein products found in your immune system (antibodies) that attack foreign substances (antigens) on leukemic cells. Gemtuzumab ozogamicin (Mylotarg) is a monoclonal antibody linked to a chemical toxin that attaches to AML cells. It's used to treat older people with AML who don't respond to initial treatment or who relapse after successful initial treatment. Researchers are testing its effectiveness in younger people with AML. Bone marrow transplant. This is another option for consolidation therapy for people at high risk of relapse or
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for treating relapse when it occurs. This procedure allows someone with leukemia to re-establish healthy stem cells by replacing their leukemic bone marrow with leukemiafree marrow. If you choose this treatment, you'll receive very high doses of chemotherapy or radiation therapy to destroy your leukemia-producing bone marrow. This marrow is then replaced by bone marrow from a compatible donor (allogeneic transplant). In some cases, you may also be able to use your own bone marrow for transplant (autologous transplant). This is possible if you go into remission and then save healthy bone marrow for a future transplant. Stem cell transplant. Stem cell transplant is also used for consolidation therapy. It's similar to bone marrow transplant except the stem cells are collected from circulating blood (peripheral blood), rather than from the bone marrow, thanks to a medication that causes larger numbers of stem cells to be released from the bone marrow. The cells used for transplant can be your own healthy cells, or they can be collected from a compatible donor. This procedure is used more frequently than bone marrow transplant because of shortened recovery times and possible decreased risk of leukemia recurrence.

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

Coping skills
Over the past several decades, doctors have made good progress in treating people with acute myelogenous leukemia, and research continues. But that doesn't necessarily make the diagnosis any less scary. Acute myelogenous leukemia is an aggressive form of cancer that typically demands quick decision making. That leaves people with a brand-new diagnosis scrambling to make hasty choices about a disease that they can barely pronounce let alone understand. Here are some tips for coping:

Get down to particulars. The term "leukemia" can be confusing because it refers to a batch of cancers that aren't all that similar except for the fact that they affect
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the bone marrow and blood. You can waste a lot of time researching information that doesn't apply to your kind of leukemia. To avoid that, ask your doctor to write down as much information about your specific disease as possible. Then narrow your search for information accordingly. Write down questions you want to ask your doctor before each appointment, and look for information in your local library and on the Internet. Good sources include the National Cancer Institute, the American Cancer Society and The Leukemia & Lymphoma Society.

Lean on family and friends. It can be tough to talk about your diagnosis, and you'll likely get a range of reactions when you share the news. But talking about your diagnosis can be helpful. So can the outpouring of practical help that often results. Take care of yourself. It's easy to get caught up in the sterile system of tests, treatments and procedures. But it's important to take care of yourself, not just the cancer. Try to make time for yoga, gardening, cooking or other favorite diversions.