21st Century Adult Cancer Sourcebook: Adult Acute Myeloid Leukemia (AML), ANLL, Myelogenous or Myeloblastic Leukemia - Clinical Data for Patients, Families, and Physicians
Edition 1.0 - September 2011
National Cancer Institute
Smashwords Edition
Copyright 2011 Progressive Management
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PART ONE
Chapter 1A: AML Patient Information
Chapter 2A: AML Health Professional Information
Chapter 3A: AML Drug Information
Chapter 4A: AML-related Topics
Chapter 5A: AML-related Clinical Trials
PART TWO
Chapter 1B: Levels of Evidence for Adult and Pediatric Cancer Treatment Studies (NCI)
Chapter 2B: Glossary of Clinical Trial Terms
Chapter 3B: Clinical Trials Background Information
Chapter 4B: Cancer Clinical Trials -The Basic Workbook
Chapter 5B: Cancer Clinical Trials - The In-Depth Program
Chapter 6B: Clinical Trials at NIH
Chapter 7B: How To Find A Cancer Treatment Trial: A Ten Step Guide
Chapter 8B: Taking Part in Cancer Treatment Research Studies
Chapter 9B: Cancer Clinical Trials
Chapter 10B: Access to Investigational Drugs
Chapter 12B: Taking Time: Support for People with Cancer
Chapter 13B: Facing Forward - Life After Cancer Treatment
Chapter 14B: Chemotherapy and You
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PART ONE
Chapter 1A: AML Patient Information
Adult Acute Myeloid Leukemia Treatment
Last Modified: 09/01/2011
Patient Version
General Information About Adult Acute Myeloid Leukemia
Key Points for This Section
Adult acute myeloid leukemia (AML) is a type of cancer in which the bone marrow makes abnormal myeloblasts (a type of white blood cell), red blood cells, or platelets.
There are different subtypes of AML.
Smoking, previous chemotherapy treatment, and exposure to radiation may affect the risk of developing adult AML.
Possible signs of adult AML include fever, feeling tired, and easy bruising or bleeding.
Tests that examine the blood and bone marrow are used to detect (find) and diagnose adult AML.
Certain factors affect prognosis (chance of recovery) and treatment options.
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Adult acute myeloid leukemia (AML) is a type of cancer in which the bone marrow makes abnormal myeloblasts (a type of white blood cell), red blood cells, or platelets.
Adult acute myeloid leukemia (AML) is a cancer of the blood and bone marrow. This type of cancer usually gets worse quickly if it is not treated. It is the most common type of acute leukemia in adults. AML is also called acute myelogenous leukemia, acute myeloblastic leukemia, acute granulocytic leukemia, and acute nonlymphocytic leukemia.
Normally, the bone marrow makes blood stem cells (immature cells) that develop into mature blood cells over time. A blood stem cell may become a myeloid stem cell or a lymphoid stem cell. The lymphoid stem cell develops into a white blood cell. The myeloid stem cell develops into one of three types of mature blood cells:
Red blood cells that carry oxygen and other materials to all tissues of the body.
White blood cells that fight infection and disease.
Platelets that help prevent bleeding by causing blood clots to form.
Blood cell development. A blood stem cell goes through several steps to become a red blood cell, platelet, or white blood cell.
In AML, the myeloid stem cells usually develop into a type of immature white blood cell called myeloblasts (or myeloid blasts). The myeloblasts in AML are abnormal and do not become healthy white blood cells. Sometimes in AML, too many stem cells develop into abnormal red blood cells or platelets. These abnormal white blood cells, red blood cells, or platelets are also called leukemia cells or blasts. Leukemia cells can build up in the bone marrow and blood so there is less room for healthy white blood cells, red blood cells, and platelets. When this happens, infection, anemia, or easy bleeding may occur. The leukemia cells can spread outside the blood to other parts of the body, including the central nervous system (brain and spinal cord), skin, and gums.
There are different subtypes of AML.
Most AML subtypes are based on how mature (developed) the cancer cells are at the time of diagnosis and how different they are from normal cells.
Acute promyelocytic leukemia (APL) is a subtype of AML that occurs when parts of two genes stick together. APL usually occurs in middle-aged adults. Symptoms of APL may include both bleeding and forming blood clots.
Smoking, previous chemotherapy treatment, and exposure to radiation may affect the risk of developing adult AML.
Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. People who think they may be at risk should discuss this with their doctor. Possible risk factors for AML include the following:
Being male.
Smoking, especially after age 60.
Having had treatment with chemotherapy or radiation therapy in the past.
Having had treatment for childhood acute lymphoblastic leukemia (ALL) in the past.
Being exposed to atomic bomb radiation or the chemical benzene.
Having a history of a blood disorder such as myelodysplastic syndrome.
Possible signs of adult AML include fever, feeling tired, and easy bruising or bleeding.
The early signs of AML may be like those caused by the flu or other common diseases. A doctor should be consulted if any of the following problems occur:
Fever.
Shortness of breath.
Easy bruising or bleeding.
Petechiae (flat, pinpoint spots under the skin caused by bleeding).
Weakness or feeling tired.
Weight loss or loss of appetite.
Tests that examine the blood and bone marrow are used to detect (find) and diagnose adult AML.
The following tests and procedures may be used:
Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
Complete blood count (CBC): A procedure in which a sample of blood is drawn and checked for the following:
The number of red blood cells, white blood cells, and platelets.
The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.
The portion of the sample made up of red blood cells.
Complete blood count (CBC). Blood is collected by inserting a needle into a vein and allowing the blood to flow into a tube. The blood sample is sent to the laboratory and the red blood cells, white blood cells, and platelets are counted. The CBC is used to test for, diagnose, and monitor many different conditions.
Peripheral blood smear: A procedure in which a sample of blood is checked for the presence of blast cells, number and kinds of white blood cells, the number of platelets, and changes in the shape of blood cells.
Bone marrow aspiration and biopsy: The removal of bone marrow, blood, and a small piece of bone by inserting a hollow needle into the hipbone or breastbone. A pathologist views the bone marrow, blood, and bone under a microscope to look for signs of cancer.
Bone marrow aspiration and biopsy. After a small area of skin is numbed, a Jamshidi needle (a long, hollow needle) is inserted into the patient’s hip bone. Samples of blood, bone, and bone marrow are removed for examination under a microscope.
Cytogenetic analysis: A laboratory test in which the cells in a sample of blood or bone marrow are viewed under a microscope to look for certain changes in the chromosomes. Other tests, such as fluorescence in situ hybridization (FISH), may also be done to look for certain changes in the chromosomes.
Immunophenotyping: A process used to identify cells, based on the types of antigens or markers on the surface of the cell. This process is used to diagnose the subtype of AML by comparing the cancer cells to normal cells of the immune system. For example, a cytochemistry study may test the cells in a sample of tissue using chemicals (dyes) to look for certain changes in the sample. A chemical may cause a color change in one type of leukemia cell but not in another type of leukemia cell.
Reverse transcription – polymerase chain reaction test (RT–PCR): A laboratory test in which cells in a sample of tissue are studied using chemicals to look for certain changes in the structure or function of genes. This test is used to diagnose certain types of AML including acute promyelocytic leukemia (APL).
Certain factors affect prognosis (chance of recovery) and treatment options.
The prognosis (chance of recovery) and treatment options depend on:
The age of the patient.
The subtype of AML.
Whether the patient received chemotherapy in the past to treat a different cancer.
Whether there is a history of a blood disorder such as myelodysplastic syndrome.
Whether the cancer has spread to the central nervous system.
Whether the cancer has been treated before or recurred (come back).
It is important that acute leukemia be treated right away.
Glossary Terms
abnormal (ab-NOR-mul) Not normal. An abnormal lesion or growth may be cancer, premalignant (likely to become cancer), or benign (not cancer).
acute leukemia (uh-KYOOT loo-KEE-mee-uh) A rapidly progressing cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of white blood cells to be produced and enter the blood stream.
acute lymphoblastic leukemia (uh-KYOOT LIM-foh-BLAS-tik loo-KEE-mee-uh) An aggressive (fast-growing) type of leukemia (blood cancer) in which too many lymphoblasts (immature white blood cells) are found in the blood and bone marrow. Also called acute lymphocytic leukemia and ALL.
acute myeloid leukemia (uh-KYOOT MY-eh-loyd loo-KEE-mee-uh) An aggressive (fast-growing) disease in which too many myeloblasts (immature white blood cells that are not lymphoblasts) are found in the bone marrow and blood. Also called acute myeloblastic leukemia, acute myelogenous leukemia, acute nonlymphocytic leukemia, AML, and ANLL.
acute promyelocytic leukemia (uh-KYOOT PRO-MY-eh-loh-SIH-tik loo-KEE-mee-uh) An aggressive (fast-growing) type of acute myeloid leukemia in which there are too many immature blood-forming cells in the blood and bone marrow. It is usually marked by an exchange of parts of chromosomes 15 and 17. Also called APL and promyelocytic leukemia.
anemia (uh-NEE-mee-uh) A condition in which the number of red blood cells is below normal.
antigen (AN-tih-jen) Any substance that causes the body to make a specific immune response.
benzene (BEN-zeen) A chemical that is used widely by the chemical industry, and is also found in tobacco smoke, vehicle emissions, and gasoline fumes. Exposure to benzene may increase the risk of developing leukemia.
blast (blast) An immature blood cell.
blood (blud) A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.
blood clot (blud klot) A mass of blood that forms when blood platelets, proteins, and cells stick together. When a blood clot is attached to the wall of a blood vessel, it is called a thrombus. When it moves through the bloodstream and blocks the flow of blood in another part of the body, it is called an embolus.
bone marrow (bone MAYR-oh) The soft, sponge-like tissue in the center of most bones. It produces white blood cells, red blood cells, and platelets.
bone marrow aspiration (bone MAYR-oh AS-pih-RAY-shun) A procedure in which a small sample of bone marrow is removed, usually from the hip bone, breastbone, or thigh bone. A small area of skin and the surface of the bone underneath are numbed with an anesthetic. Then, a special wide needle is pushed into the bone. A sample of liquid bone marrow is removed with a syringe attached to the needle. The bone marrow is sent to a laboratory to be looked at under a microscope. This procedure may be done at the same time as a bone marrow biopsy.
bone marrow biopsy (bone MAYR-oh BY-op-see) A procedure in which a small sample of bone with bone marrow inside it is removed, usually from the hip bone. A small area of skin and the surface of the bone underneath are numbed with an anesthetic. Then, a special, wide needle is pushed into the bone and rotated to remove a sample of bone with the bone marrow inside it. The sample is sent to a laboratory to be looked at under a microscope. This procedure may be done at the same time as a bone marrow aspiration.
cancer (KAN-ser) A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.
cell (sel) The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.
central nervous system (SEN-trul NER-vus SIS-tem) The brain and spinal cord. Also called CNS.
chemical (KEH-mih-kul) A substance made up of elements, such as hydrogen or sodium.
chemotherapy (KEE-moh-THAYR-uh-pee) Treatment with drugs that kill cancer cells.
chromosome (KROH-muh-some) Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes.
complete blood count (kum-PLEET blud kownt) A test to check the number of red blood cells, white blood cells, and platelets in a sample of blood. Also called blood cell count and CBC.
cytogenetics (SY-toh-jeh-NEH-tix) The study of chromosomes and chromosomal abnormalities.
diagnosis (DY-ug-NOH-sis) The process of identifying a disease, such as cancer, from its signs and symptoms.
disorder (dis-OR-der) In medicine, a disturbance of normal functioning of the mind or body. Disorders may be caused by genetic factors, disease, or trauma.
fluorescence in situ hybridization (floor-EH-sents in SY-too HY-brih-dih-ZAY-hun) A laboratory technique used to look at genes or chromosomes in cells and tissues. Pieces of DNA that contain a fluorescent dye are made in the laboratory and added to cells or tissues on a glass slide. When these pieces of DNA bind to specific genes or areas of chromosomes on the slide, they light up when viewed under a microscope with a special light. Also called FISH.
gene (jeen) The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein.
hemoglobin (HEE-moh-GLOH-bin) The substance inside red blood cells that binds to oxygen in the lungs and carries it to the tissues.
immune system (ih-MYOON SIS-tem) The complex group of organs and cells that defends the body against infections and other diseases.
immunophenotyping (IH-myoo-noh-FEE-noh-ty-ping) A process used to identify cells, based on the types of antigens or markers on the surface of the cell. This process is used to diagnose specific types of leukemia and lymphoma by comparing the cancer cells to normal cells of the immune system.
infection (in-FEK-shun) Invasion and multiplication of germs in the body. Infections can occur in any part of the body and can spread throughout the body. The germs may be bacteria, viruses, yeast, or fungi. They can cause a fever and other problems, depending on where the infection occurs. When the body’s natural defense system is strong, it can often fight the germs and prevent infection. Some cancer treatments can weaken the natural defense system.
laboratory test (LA-bruh-tor-ee...) A medical procedure that involves testing a sample of blood, urine, or other substance from the body. Tests can help determine a diagnosis, plan treatment, check to see if treatment is working, or monitor the disease over time.
leukemia (loo-KEE-mee-uh) Cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of blood cells to be produced and enter the bloodstream.
lymphoid (LIM-foyd) Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop.
marker (MAR-ker) A diagnostic indication that disease may develop.
myelodysplastic syndromes (MY-eh-loh-dis-PLAS-tik SIN-dromz) A group of diseases in which the bone marrow does not make enough healthy blood cells. Also called preleukemia and smoldering leukemia.
myeloid (MY-eh-loyd) Having to do with or resembling the bone marrow. May also refer to certain types of hematopoietic (blood-forming) cells found in the bone marrow. Sometimes used as a synonym for myelogenous; for example, acute myeloid leukemia and acute myelogenous leukemia are the same disease.
oxygen (OK-sih-jen) A colorless, odorless gas. It is needed for animal and plant life. Oxygen that is breathed in enters the blood from the lungs and travels to the tissues.
pathologist (puh-THAH-loh-jist) A doctor who identifies diseases by studying cells and tissues under a microscope.
peripheral blood smear (peh-RIH-feh-rul blud smeer) A procedure in which a sample of blood is viewed under a microscope to count different circulating blood cells (red blood cells, white blood cells, platelets, etc.) and see whether the cells look normal.
petechiae (peh-TEE-kee-ee) Pinpoint, unraised, round red spots under the skin caused by bleeding.
physical examination (FIH-zih-kul eg-ZA-mih-NAY-shun) An exam of the body to check for general signs of disease.
platelet (PLATE-let) A tiny piece of a cell found in the blood that breaks off from a large cell found in the bone marrow. Platelets help wounds heal and prevent bleeding by forming blood clots. Also called thrombocyte.
polymerase chain reaction (puh-LIM-eh-rays chayn ree-AK-shun) A laboratory method used to make many copies of a specific DNA sequence. Also called PCR.
prognosis (prog-NO-sis) The likely outcome or course of a disease; the chance of recovery or recurrence.
protein (PROH-teen) A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.
radiation (RAY-dee-AY-shun) Energy released in the form of particle or electromagnetic waves. Common sources of radiation include radon gas, cosmic rays from outer space, medical x-rays, and energy given off by a radioisotope (unstable form of a chemical element that releases radiation as it breaks down and becomes more stable).
radiation therapy (RAY-dee-AY-shun THAYR-uh-pee) The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called irradiation and radiotherapy.
red blood cell (red blud sel) A cell that carries oxygen to all parts of the body. Also called erythrocyte and RBC.
reverse transcription (ree-VERS tran-SKRIP-shun) In biology, the process in cells by which an enzyme makes a copy of DNA from RNA. The enzyme that makes the DNA copy is called reverse transcriptase and is found in retroviruses, such as the human immunodeficiency virus (HIV). Reverse transcription can also be carried out in the laboratory.
risk factor (... FAK-ter) Something that increases the chance of developing a disease. Some examples of risk factors for cancer are age, a family history of certain cancers, use of tobacco products, being exposed to radiation or certain chemicals, infection with certain viruses or bacteria, and certain genetic changes.
spinal cord (SPY-nul kord) A column of nerve tissue that runs from the base of the skull down the back. It is surrounded by three protective membranes, and is enclosed within the vertebrae (back bones). The spinal cord and the brain make up the central nervous system, and spinal cord nerves carry most messages between the brain and the rest of the body.
stem cell (stem sel) A cell from which other types of cells develop. For example, blood cells develop from blood-forming stem cells.
symptom (SIMP-tum) An indication that a person has a condition or disease. Some examples of symptoms are headache, fever, fatigue, nausea, vomiting, and pain.
tissue (TIH-shoo) A group or layer of cells that work together to perform a specific function.
white blood cell (hwite blud sel) A type of immune cell. Most white blood cells are made in the bone marrow and are found in the blood and lymph tissue. White blood cells help the body fight infections and other diseases. Granulocytes, monocytes, and lymphocytes are white blood cells. Also called leukocyte and WBC.
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Stages of Adult Acute Myeloid Leukemia
Key Points for This Section
Once adult acute myeloid leukemia (AML) has been diagnosed, tests are done to find out if the cancer has spread to other parts of the body.
There are three ways that cancer spreads in the body.
There is no standard staging system for adult AML.
Once adult acute myeloid leukemia (AML) has been diagnosed, tests are done to find out if the cancer has spread to other parts of the body.
The extent or spread of cancer is usually described as stages. In adult acute myeloid leukemia (AML), the subtype of AML and whether the leukemia has spread outside the blood and bone marrow are used instead of the stage to plan treatment. The following tests and procedures may be used to determine if the leukemia has spread:
Lumbar puncture: A procedure used to collect cerebrospinal fluid from the spinal column. This is done by placing a needle into the spinal column. This procedure is also called an LP or spinal tap.
Lumbar puncture. A patient lies in a curled position on a table. After a small area on the lower back is numbed, a spinal needle (a long, thin needle) is inserted into the lower part of the spinal column to remove cerebrospinal fluid (CSF, shown in blue). The fluid may be sent to a laboratory for testing.
CT scan (CAT scan): A procedure that makes a series of detailed pictures of the abdomen, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
There are three ways that cancer spreads in the body.
When cancer cells spread outside the blood, a solid tumor may form. This process is called metastasis. The three ways that cancer cells spread in the body are:
Through the blood. Cancer cells travel through the blood, invade solid tissues in the body, such as the brain or heart, and form a solid tumor.
Through the lymph system. Cancer cells invade the lymph system, travel through the lymph vessels, and form a solid tumor in other parts of the body.
Through solid tissue. Cancer cells that have formed a solid tumor spread to tissues in the surrounding area.
The new (metastatic) tumor is the same type of cancer as the primary cancer. For example, if leukemia cells spread to the brain, the cancer cells in the brain are actually leukemia cells. The disease is metastatic leukemia, not brain cancer.
There is no standard staging system for adult AML.
The disease is described as untreated, in remission, or recurrent.
Untreated adult AML
In untreated adult AML, the disease is newly diagnosed. It has not been treated except to relieve symptoms such as fever, bleeding, or pain, and the following are true:
The complete blood count is abnormal.
At least 20% of the cells in the bone marrow are blasts (leukemia cells).
There are signs or symptoms of leukemia.
Adult AML in remission
In adult AML in remission, the disease has been treated and the following are true:
The complete blood count is normal.
Less than 5% of the cells in the bone marrow are blasts (leukemia cells).
There are no signs or symptoms of leukemia in the brain and spinal cord or elsewhere in the body.
Recurrent Adult AML
Recurrent AML is cancer that has recurred (come back) after it has been treated. The AML may come back in the blood or bone marrow.
Glossary Terms
abnormal (ab-NOR-mul) Not normal. An abnormal lesion or growth may be cancer, premalignant (likely to become cancer), or benign (not cancer).
acute myeloid leukemia (uh-KYOOT MY-eh-loyd loo-KEE-mee-uh) An aggressive (fast-growing) disease in which too many myeloblasts (immature white blood cells that are not lymphoblasts) are found in the bone marrow and blood. Also called acute myeloblastic leukemia, acute myelogenous leukemia, acute nonlymphocytic leukemia, AML, and ANLL.
AML - An aggressive (fast-growing) disease in which too many myeloblasts (immature white blood cells that are not lymphoblasts) are found in the bone marrow and blood. Also called acute myeloblastic leukemia, acute myelogenous leukemia, acute myeloid leukemia, acute nonlymphocytic leukemia, and ANLL.
blast (blast) An immature blood cell.
blood (blud) A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.
bone marrow (bone MAYR-oh) The soft, sponge-like tissue in the center of most bones. It produces white blood cells, red blood cells, and platelets.
cell (sel) The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.
cerebrospinal fluid (seh-REE-broh-SPY-nul FLOO-id) The fluid that flows in and around the hollow spaces of the brain and spinal cord, and between two of the meninges (the thin layers of tissue that cover and protect the brain and spinal cord). Cerebrospinal fluid is made by tissue called the choroid plexus in the ventricles (hollow spaces) in the brain. Also called CSF.
complete blood count (kum-PLEET blud kownt) A test to check the number of red blood cells, white blood cells, and platelets in a sample of blood. Also called blood cell count and CBC.
contrast material (KON-trast muh-TEER-ee-ul) A dye or other substance that helps show abnormal areas inside the body. It is given by injection into a vein, by enema, or by mouth. Contrast material may be used with x-rays, CT scans, MRI, or other imaging tests.
CT scan (… skan) A series of detailed pictures of areas inside the body taken from different angles. The pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography scan, computerized axial tomography scan, and computerized tomography.
diagnosis (DY-ug-NOH-sis) The process of identifying a disease, such as cancer, from its signs and symptoms.
fever (FEE-ver) An increase in body temperature above normal (98.6 degrees F), usually caused by disease.
injection (in-JEK-shun) Use of a syringe and needle to push fluids or drugs into the body; often called a "shot."
leukemia (loo-KEE-mee-uh) Cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of blood cells to be produced and enter the bloodstream.
lumbar puncture (LUM-bar PUNK-cher) A procedure in which a thin needle called a spinal needle is put into the lower part of the spinal column to collect cerebrospinal fluid or to give drugs. Also called spinal tap.
lymph vessel (limf ...) A thin tube that carries lymph (lymphatic fluid) and white blood cells through the lymphatic system. Also called lymphatic vessel.
lymphatic system (lim-FA-tik SIS-tem) The tissues and organs that produce, store, and carry white blood cells that fight infections and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes, and lymphatic vessels (a network of thin tubes that carry lymph and white blood cells). Lymphatic vessels branch, like blood vessels, into all the tissues of the body.
metastasis (meh-TAS-tuh-sis) The spread of cancer from one part of the body to another. A tumor formed by cells that have spread is called a “metastatic tumor” or a “metastasis.” The metastatic tumor contains cells that are like those in the original (primary) tumor. The plural form of metastasis is metastases (meh-TAS-tuh-SEEZ).
metastatic (meh-tuh-STA-tik) Having to do with metastasis, which is the spread of cancer from the primary site (place where it started) to other places in the body.
organ (OR-gun) A part of the body that performs a specific function. For example, the heart is an organ.
primary tumor (PRY-mayr-ee TOO-mer) The original tumor.
recurrent cancer (ree-KER-ent KAN-ser) Cancer that has recurred (come back), usually after a period of time during which the cancer could not be detected. The cancer may come back to the same place as the original (primary) tumor or to another place in the body. Also called recurrence.
remission (reh-MIH-shun) A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although cancer still may be in the body.
solid tumor (SAH-lid TOO-mer) An abnormal mass of tissue that usually does not contain cysts or liquid areas. Solid tumors may be benign (not cancer), or malignant (cancer). Different types of solid tumors are named for the type of cells that form them. Examples of solid tumors are sarcomas, carcinomas, and lymphomas. Leukemias (cancers of the blood) generally do not form solid tumors.
spinal column (SPY-nul KAH-lum) The bones, muscles, tendons, and other tissues that reach from the base of the skull to the tailbone. The spinal column encloses the spinal cord and the fluid surrounding the spinal cord. Also called backbone, spine, and vertebral column.
spinal cord (SPY-nul kord) A column of nerve tissue that runs from the base of the skull down the back. It is surrounded by three protective membranes, and is enclosed within the vertebrae (back bones). The spinal cord and the brain make up the central nervous system, and spinal cord nerves carry most messages between the brain and the rest of the body.
stage The extent of a cancer in the body. Staging is usually based on the size of the tumor, whether lymph nodes contain cancer, and whether the cancer has spread from the original site to other parts of the body.
symptom (SIMP-tum) An indication that a person has a condition or disease. Some examples of symptoms are headache, fever, fatigue, nausea, vomiting, and pain.
tissue (TIH-shoo) A group or layer of cells that work together to perform a specific function.
vein (vayn) A blood vessel that carries blood to the heart from tissues and organs in the body.
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Treatment Option Overview
Key Points for This Section
There are different types of treatment for patients with adult acute myeloid leukemia.
The treatment of adult AML usually has 2 phases.
Four types of standard treatment are used:
Chemotherapy * Radiation therapy * Stem cell transplant * Other drug therapy
New types of treatment are being tested in clinical trials.
Targeted therapy
Patients may want to think about taking part in a clinical trial.
Patients can enter clinical trials before, during, or after starting their cancer treatment.
Follow-up tests may be needed.
There are different types of treatment for patients with adult acute myeloid leukemia.
Different types of treatment are available for patients with adult acute myeloid leukemia (AML). Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.
The treatment of adult AML usually has 2 phases.
The 2 treatment phases of adult AML are:
Remission induction therapy: This is the first phase of treatment. Its purpose is to kill the leukemia cells in the blood and bone marrow. This puts the leukemia into remission.
Post-remission therapy: This is the second phase of treatment. It begins after the leukemia is in remission. The purpose of post-remission therapy is to kill any remaining leukemia cells that may not be active but could begin to regrow and cause a relapse. This phase is also called remission continuation therapy.
Four types of standard treatment are used:
Chemotherapy
Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid (intrathecal chemotherapy), an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). Intrathecal chemotherapy may be used to treat adult AML that has spread, or may spread to the brain and spinal cord. Combination chemotherapy is treatment using more than one anticancer drug. The way the chemotherapy is given depends on the subtype of the cancer being treated and whether it has spread to the brain and spinal cord.
Intrathecal chemotherapy. Anticancer drugs are injected into the intrathecal space, which is the space that holds the cerebrospinal fluid (CSF, shown in blue). There are two different ways to do this. One way, shown in the top part of the figure, is to inject the drugs into an Ommaya reservoir (a dome-shaped container that is placed under the scalp during surgery; it holds the drugs as they flow through a small tube into the brain). The other way, shown in the bottom part of the figure, is to inject the drugs directly into the CSF in the lower part of the spinal column, after a small area on the lower back is numbed.
Radiation therapy
Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.
Stem cell transplant
Stem cell transplant is a method of giving chemotherapy and replacing blood-forming cells that are abnormal or destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient or a donor and are frozen and stored. After the chemotherapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body's blood cells.
Other drug therapy
Arsenic trioxide and all-trans retinoic acid (ATRA) are anticancer drugs that kill leukemia cells, stop the leukemia cells from dividing, or help the leukemia cells mature into white blood cells. These drugs are used in the treatment of a subtype of AML called acute promyelocytic leukemia.
New types of treatment are being tested in clinical trials.
This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI Web site.
Targeted therapy
Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells. Monoclonal antibody therapy is one type of targeted therapy being studied in the treatment of adult AML.
Monoclonal antibody therapy is a cancer treatment that uses antibodies made in the laboratory from a single type of immune system cell. These antibodies can identify substances on cancer cells or normal substances that may help cancer cells grow. The antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells.
Patients may want to think about taking part in a clinical trial.
For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.
Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.
Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.
Patients can enter clinical trials before, during, or after starting their cancer treatment.
Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.
Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.
Follow-up tests may be needed.
Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.
Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.
Treatment Options for Adult Acute Myeloid Leukemia
Untreated Adult Acute Myeloid Leukemia
Standard treatment of untreated adult acute myeloid leukemia (AML) during the remission induction phase depends on the subtype of AML and may include the following:
Combination chemotherapy.
High-dose combination chemotherapy.
Low- dose chemotherapy.
Intrathecal chemotherapy.
All-trans retinoic acid (ATRA) plus chemotherapy for the treatment of acute promyelocytic leukemia (APL).
A clinical trial of arsenic trioxide and ATRA and combination chemotherapy for the treatment of APL.
A clinical trial of arsenic trioxide and ATRA and targeted therapy for the treatment of APL.
Adult Acute Myeloid Leukemia in Remission
Standard treatment of adult AML during the remission phase depends on the subtype of AML and may include the following:
Combination chemotherapy.
High-dose chemotherapy, with or without radiation therapy, and stem cell transplant using the patient's stem cells.
High-dose chemotherapy and stem cell transplant using donor stem cells.
One of the treatments being studied in clinical trials for adult AML in remission is arsenic trioxide.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with adult acute myeloid leukemia in remission. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.
Recurrent Adult Acute Myeloid Leukemia
There is no standard treatment for recurrent adult AML. Treatment depends on the subtype of AML and may include the following:
Combination chemotherapy.
Targeted therapy with monoclonal antibodies.
Stem cell transplant.
Arsenic trioxide therapy.
* * * * * * * * * * * *
Chapter 2A: AML Health Professional Information
Adult Acute Myeloid Leukemia Treatment
General Information About Adult Acute Myeloid Leukemia
Incidence and Mortality
Note: Estimated new cases and deaths from acute myeloid leukemia (AML) in the United States in 2011:[1]
• New cases: 12,950.
• Deaths: 9,050.
Advances in the treatment of AML (also called acute myelogenous leukemia, acute nonlymphocytic leukemia, or ANLL) have resulted in substantially improved complete remission rates.[2] Treatment should be sufficiently aggressive to achieve complete remission because partial remission offers no substantial survival benefit. Approximately 60% to 70% of adults with AML can be expected to attain complete remission status following appropriate induction therapy. More than 25% of adults with AML (about 45% of those who attain complete remission) can be expected to survive 3 or more years and may be cured. Remission rates in adult AML are inversely related to age, with an expected remission rate of more than 65% for those younger than 60 years. Data suggest that once attained, duration of remission may be shorter in older patients. Increased morbidity and mortality during induction appear to be directly related to age. Other adverse prognostic factors include central nervous system involvement with leukemia, systemic infection at diagnosis, elevated white blood cell count (>100,000/mm3), treatment-induced AML, and history of myelodysplastic syndromes or another antecedent hematological disorder. Patients with leukemias that express the progenitor cell antigen CD34 and/or the P-glycoprotein (MDR1 gene product) have an inferior outcome.[3-5] AML associated with an internal tandem duplication of the FLT3 gene (FLT3/ ITD mutation) has an inferior outcome that is attributed to a higher relapse rate.[6,7]
Cytogenetic analysis provides some of the strongest prognostic information available, predicting outcome of both remission induction and postremission therapy, as seen in a trial from the Southwest Oncology Group (SWOG) and the Eastern Cooperative Oncology Group (ECOG) (E-3489).[8] Cytogenetic abnormalities that indicate a good prognosis include t(8; 21), inv(16) or t(16;16), and t(15;17). Normal cytogenetics portend average-risk AML. Patients with AML that is characterized by deletions of the long arms or monosomies of chromosomes 5 or 7; by translocations or inversions of chromosome 3, t(6; 9), t(9; 22); or by abnormalities of chromosome 11q23 have particularly poor prognoses with chemotherapy. These cytogenetic subgroups, as seen in the trial from the Medical Research Council (MRC-LEUK-AML11), predict clinical outcome in older patients with AML as well as in younger patients.[9] The fusion genes formed in t(8; 21) and inv(16) can be detected by reverse transcriptase-polymerase chain reaction (RT-PCR) or fluorescence in situ hybridization (FISH), which will indicate the presence of these genetic alterations in some patients in whom standard cytogenetics was technically inadequate. RT-PCR does not appear to identify significant numbers of patients with good risk fusion genes who have normal cytogenetics.[10]
The classification of AML has been revised by a group of pathologists and clinicians under the auspices of the World Health Organization (WHO).[11] While elements of the French-American-British classification have been retained (i.e., morphology, immunophenotype, cytogenetics and clinical features), the WHO classification incorporates more recent discoveries regarding the genetics and clinical features of AML in an attempt to define entities that are biologically homogeneous and that have prognostic and therapeutic relevance.[11-13] Each criterion has prognostic and treatment implications but, for practical purposes, antileukemic therapy is similar for all subtypes.
A long-term follow-up of 30 patients who had AML that was in remission for at least 10 years has demonstrated a 13% incidence of secondary malignancies. Of 31 long-term female survivors of AML or acute lymphoblastic leukemia younger than 40 years, 26 resumed normal menstruation following completion of therapy. Among 36 live offspring of survivors, 2 congenital problems occurred.[14]
The differentiation of AML from acute lymphocytic leukemia has important therapeutic implications. Histochemical stains and cell surface antigen determinations aid in discrimination.
References
1. American Cancer Society.: Cancer Facts and Figures 2011. Atlanta, Ga: American Cancer Society, 2011. Also available online. Last accessed July 27, 2011.
2. American Cancer Society.: Cancer Facts and Figures-1998. Atlanta, Ga: American Cancer Society,1998.
3. Myint H, Lucie NP: The prognostic significance of the CD34 antigen in acute myeloid leukaemia. Leuk Lymphoma 7 (5-6): 425-9, 1992.
4. Geller RB, Zahurak M, Hurwitz CA, et al.: Prognostic importance of immunophenotyping in adults with acute myelocytic leukaemia: the significance of the stem-cell glycoprotein CD34 (My10) Br J Haematol 76 (3): 340-7, 1990.
5. Campos L, Guyotat D, Archimbaud E, et al.: Clinical significance of multidrug resistance P-glycoprotein expression on acute nonlymphoblastic leukemia cells at diagnosis. Blood 79 (2): 4736, 1992.
6. Kottaridis PD, Gale RE, Frew ME, et al.: The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood 98 (6): 1752-9, 2001.
7. Yanada M, Matsuo K, Suzuki T, et al.: Prognostic significance of FLT3 internal tandem duplication and tyrosine kinase domain mutations for acute myeloid leukemia: a meta-analysis. Leukemia 19 (8): 1345-9, 2005.
8. Slovak ML, Kopecky KJ, Cassileth PA, et al.: Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood 96 (13): 4075-83, 2000.
9. Grimwade D, Walker H, Harrison G, et al.: The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial. Blood 98 (5): 1312-20, 2001.
10. Mrozek K, Prior TW, Edwards C, et al.: Comparison of cytogenetic and molecular genetic detection of t(8;21) and inv(16) in a prospective series of adults with de novo acute myeloid leukemia: a Cancer and Leukemia Group B Study. J Clin Oncol 19 (9): 2482-92, 2001.
11. Brunning RD, Matutes E, Harris NL, et al.: Acute myeloid leukaemia: introduction. In: Jaffe ES, Harris NL, Stein H, et al., eds.: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press, 2001. World Health Organization Classification of Tumours, 3, pp 77-80.
12. Bennett JM, Catovsky D, Daniel MT, et al.: Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol 33 (4): 451-8, 1976.
13. Cheson BD, Cassileth PA, Head DR, et al.: Report of the National Cancer Institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia. J Clin Oncol 8 (5): 813-9, 1990.
14. Micallef IN, Rohatiner AZ, Carter M, et al.: Long-term outcome of patients surviving for more than ten years following treatment for acute leukaemia. Br J Haematol 113 (2): 443-5, 2001.
Classification of Adult Acute Myeloid Leukemia
Acute Myeloid Leukemia (AML) With Characteristic Genetic Abnormalities
Acute Myeloid Leukemia With Mutations of FLT3, NPM1, or CMBPA
Acute Myeloid Leukemia With Multilineage Dysplasia
Acute Myeloid Leukemias and Myelodysplastic Syndromes, Therapy Related Acute Myeloid Leukemia Not Otherwise Categorized
Acute Leukemias of Ambiguous Lineage
Note: Some citations in the text of this section are followed by a level of evidence. The editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy.
The World Health Organization (WHO) classification of acute myeloid leukemia (AML) incorporates and interrelates morphology, cytogenetics, molecular genetics, and immunologic markers in an attempt to construct a classification that is universally applicable and prognostically valid.[l] In the older French-American-British (FAB) criteria, the classification of AML is solely based upon morphology as determined by the degree of differentiation along different cell lines and the extent of cell maturation.[2,3]
Under the WHO classification, the category "acute myeloid leukemia not otherwise categorized" is morphology-based and reflects the FAB classification with a few significant modifications.[2,3] The most significant difference between the WHO and FAB classifications is the WHO recommendation that the requisite blast percentage for the diagnosis of AML be at least 20% blasts in the blood or bone marrow. The FAB scheme required the blast percentage in the blood or bone marrow to be at least 30%. This threshold value for blast percentage eliminated the category "refractory anemia with excess blasts in transformation" (RAEB-t) found in the FAB classification of myelodysplastic syndromes (MDS), where RAEB-t is defined by a marrow blast percentage between 20% and 29%. In the WHO classification, RAEB-t is no longer considered a distinct clinical entity, and is instead included within the broader category "AML with multilineage dysplasia" as "AML with multilineage dysplasia following a myelodysplastic syndrome."[4]
Although this lowering of the blast threshold has been met with some criticism, several studies indicate that survival patterns for cases with 20% to 29% blasts are similar to survival patterns for cases with 30% or more blasts in the bone marrow.[5-9] The diagnosis of AML in itself does not represent a therapeutic mandate. The decision to treat should be based on other factors including patient age, previous history of MDS, clinical findings, disease progression, in addition to the blast percentage, and most importantly, patient preference.
Several groups have begun to investigate the use of gene expression profiling (GEP) using microarrays to augment current diagnostic and prognostic studies for AML. Distinct subsets can be identified using GEP that correspond to known cytogenetic and molecular abnormalities. The positive predictive value appears to be sufficiently powerful to be clinically useful only for patients with the t(8;21) and inv(16) (now referred to as core-binding factor leukemias) and acute promyelocytic leukemia with the t(15;17). GEP identified several cases of core-binding factor leukemias that were not diagnosed using conventional cytogenetics. [10-12]
In the following outline and discussion, the older FAB classifications are noted where appropriate.
• AML with characteristic genetic abnormalities.
AML with t(8; 21)(q22;q22); (AML/ETO).
AML with inv(16)(p13q22) or t(16;16)(p13; q22); (CBFP/MYH11).
Acute promyelocytic leukemia (AML with t(15;17)(q22; q12); (PML/RARa) and variants).
AML with 11q23 (MLL) abnormalities.
• AML with an FLT3 mutation (not in the WHO classification scheme).
• AML with multilineage dysplasia.
• AML and MDS, therapy related.
Alkylating agent-related AML and MDS.
Topoisomerase II inhibitor-related AML.
• AML not otherwise categorized.
Acute myeloblastic leukemia, minimally differentiated (FAB Classification M0).
Acute myeloblastic leukemia without maturation (FAB Classification M1).
Acute myeloblastic leukemia with maturation (FAB Classification M2).
Acute myelomonocytic leukemia (AMML) (FAB Classification M4).
Acute monoblastic leukemia and acute monocytic leukemia (FAB classifications M5a and M5b).
Acute erythroid leukemias (FAB classifications M6a and M6b).
Acute megakaryoblastic leukemia (FAB Classification M7).
• AML/transient myeloproliferative disorder in Down syndrome.
Acute basophilic leukemia.
Acute panmyelosis with myelofibrosis.
Myeloid sarcoma.
• Acute leukemias of ambiguous lineage.
Acute Myeloid Leukemia (AML) With Characteristic Genetic Abnormalities
This category is characterized by characteristic genetic abnormalities and frequently high rates of remission and favorable prognoses with the notable exception of those with 11q23 abnormalities.[13] The reciprocal translocations t(8; 21), inv(16) or t(16;16), t(15; 17), and translocations involving the 11q23 breakpoint are the most commonly identified genetic abnormalities. These structural chromosome rearrangements result in the formation of fusion genes that encode chimeric proteins that may contribute to the initiation or progression of leukemogenesis. Many of these translocations are detected by reverse transcriptase-polymerase chain reaction (RT-PCR) or fluorescence in situ hybridization (FISH), which has a higher sensitivity than cytogenetics. Other recurring cytogenetic abnormalities are less common and described below in AML not otherwise categorized.
Acute myeloid leukemia with t(8; 21)(q22; q22); (AML/ETO)
AML with the translocation t(8; 21)(q22; q22) (occurring most commonly in FAB classification M2) is one of the most common genetic aberrations in AML and accounts for 5% to 12% of cases of AML and 33% of karyotypically abnormal cases of acute myeloblastic leukemia with maturation.[14] Myeloid sarcomas (chloromas) may be present and may be associated with a bone marrow blast percentage of less than 20%.
Common morphologic features include the following:
• Large blasts with abundant basophilic cytoplasm, often containing numerous azurophilic granules.
• A few blasts in some cases show very large granules (pseudo Chediak-Higashi granules).
• Auer rods, which may be detected in mature neutrophils.
• Smaller blasts, predominantly in the peripheral blood.
• Promyelocytes, myelocytes, and mature neutrophils with variable dysplasia in the bone marrow.
• Abnormal nuclear segmentation (pseudo Pelger-Huet nuclei) and/or cytoplasmic staining abnormalities.
• Increased eosinophil precursors.
• Reduced or absent monocytes.
• Normal erythroblasts and megakaryocytes.
AML with maturation (FAB classification M2) is the most common morphologic type correlating with t(8; 21). Rarely, AML with this translocation presents with a bone marrow blast percentage less than 20%.[13]
The translocation t(8; 21)(q22; q22) involves the AML1 gene, also known as RUNX1, which encodes core binding factor-alpha (CBF-alpha), and the ETO (eight-twenty-one) gene.[13,15] The AML1/ETO fusion transcript is consistently detected in patients with t(8; 21) AML. This type of AML is usually associated with a good response to chemotherapy and a high complete remission rate with long-term survival when treated with high-dose cytarabine in the postremission phase as in the Cancer and Leukemia Group B (CLB-9022 and CLB-8525) trials.[16-19] Additional chromosome abnormalities are common, e.g., loss of a sex chromosome and del(9)(q22). Expression of the neural cell adhesion molecule CD56 appears to be an adverse prognostic indicator.[20,21]
Acute myeloid leukemia with inv(16)(p13; q22) or t(16; 16)(p13; q22); (CBFfi/MYHH)
AML with inv(16)(p13; q22) or t(16; 16)(p13; q22) is found in approximately 10% to 12% of all cases of AML, predominantly in younger patients.[13,22] Morphologically, this type of AML is associated with acute myelomonocytic leukemia (FAB classification M4) with abnormal eosinophils (AMML Eo). Myeloid sarcomas may be present at initial diagnosis or at relapse.
Common morphologic features include the following:
• Monocytic and granulocytic differentiation.
• A characteristically abnormal eosinophil component with immature purple-violet eosinophil granules that may obscure cell morphology if present in great numbers.
• Auer rods in myeloblasts.
• Decreased neutrophils in bone marrow.
Most cases with this genetic abnormality have been identified as AMML Eo, but occasional cases have been reported to lack eosinophilia. As is found in rare cases of AML with t(8; 21), the bone marrow blast percentage in this AML is occasionally less than 20%.
Both inv(16)(p13; q22) and t(16; 16)(p13; q22) result in the fusion of the core-binding factor-beta (CBFP) gene at 16q22 to the smooth muscle myosin heavy chain (MYH11) gene at 16p13, thereby forming the fusion gene CBF&/MYH11 .[14] The use of FISH and RT-PCR methods may be necessary to document this fusion gene because its presence cannot be reliably documented by traditional cytogenetics banding techniques.[23] Patients with this type of AML may achieve higher complete remission rates when treated with high-dose cytarabine in the postremission phase.[16,17,19]
Acute promyelocytic leukemia [AML with t(15; 17)(q22; q12); (PML/RARa) and variants] (FAB Classification M3)
Acute promyelocytic leukemia (APL) AML with t(15; 17)(q22; q12) is an AML in which promyelocytes predominate. APL exists as two types, hypergranular or typical APL and microgranular (hypogranular) APL. APL comprises 5% to 8% of cases of AML and occurs predominately in adults in midlife.[13] Both typical and microgranular APL are commonly associated with disseminated intravascular coagulation (DIC). [24,25] In microgranular APL, unlike typical APL, the leukocyte count is very high with a rapid doubling time. [13]
Common morphologic features of typical APL include the following:
• Kidney-shaped or bilobed nuclei.
• Cytoplasm densely packed with large granules (bright pink, red, or purple in Romanowsky stains).