This Website is for Pateints only. We do not deal with Medical Institutions or Pharmaceutical Companies
Click here to go to the treatment: http://www.cancermedicines.in/treatment.php?id=71
What is acute myeloid leukemia?
Acute myeloid leukemia (AML) goes by many names, including acute myelocytic leukemia, acute myelogenous leukemia, acute granulocytic leukemia, and acute non-lymphocytic leukemia. "Acute" means that the leukemia can progress quickly, and if not treated, would probably be fatal in a few months.
AML is a cancer that starts in cells that would normally develop into different types of blood cells. Most cases of AML develop from cells that would turn into white blood cells (other than lymphocytes), but some cases of AML develop in other types of blood-forming cells.
(Acute leukemia that develops in lymphocytes is called acute lymphocytic leukemia (ALL).
AML starts in the bone marrow (the soft inner part of the bones, where new blood cells are made), but in most cases it quickly moves into the blood. It can sometimes spread to other parts of the body including the lymph nodes, liver, spleen, central nervous system (brain and spinal cord), and testicles (in males).
Other types of cancer can start in these organs and then spread to the bone marrow. But these cancers that start elsewhere and then spread to the bone marrow are not leukemia.
Normal bone marrow, blood, and lymphoid tissue
In order to understand the different types of leukemia, it helps to have some basic knowledge about the blood and lymph systems.
Bone marrow is the soft inner part of some bones such as the skull, shoulder blades, ribs, pelvis, and backbones. The bone marrow is made up of a small number of blood stem cells, more mature blood-forming cells, fat cells, and supporting tissues that help cells grow.
Blood stem cells go through a series of changes to make new blood cells. During this process, the cells develop into either lymphocytes (a kind of white blood cell) or other blood-forming cells. The other blood-forming cells can develop into 1 of the 3 main types of blood cell components:
Red blood cells
White blood cells (other than lymphocytes)
Red blood cells
Red blood cells carry oxygen from the lungs to all other tissues in the body, and take carbon dioxide back to the lungs to be removed. Anemia (having too few red blood cells in the body) typically causes a person to feel tired, weak, and short of breath because the body tissues are not getting enough oxygen.
Platelets are actually cell fragments made by a type of bone marrow cell called the megakaryocyte. Platelets are important in plugging up holes in blood vessels caused by cuts or bruises. A shortage of platelets is called thrombocytopenia. A person with thrombocytopenia may bleed and bruise easily.
White blood cells
White blood cells help the body fight infections. Lymphocytes are one type of white blood cell. The other types of white blood cells are granulocytes (neutrophils, basophils, and eosinophils) and monocytes.
Lymphocytes: These are the main cells that make up lymphoid tissue, a major part of the immune system. Lymphoid tissue is found in lymph nodes, the thymus gland, the spleen, the tonsils and adenoids, and is scattered throughout the digestive and respiratory systems and the bone marrow.
Lymphocytes develop from cells called lymphoblasts to become mature, infection-fighting cells. The 2 main types of lymphocytes are known as B lymphocytes (B cells) and T lymphocytes (T cells).
B lymphocytes protect the body from invading germs by developing (maturing) into plasma cells, which make proteins called antibodies. The antibodies attach to the germs (bacteria, viruses, and fungi), which helps other white blood cells to recognize and destroy them.
T lymphocytes can recognize cells infected by viruses and directly destroy these cells.
Granulocytes: These are white blood cells that have granules in them, which are spots that can be seen under the microscope. These granules contain enzymes and other substances that can destroy germs, such as bacteria. The 3 types of granulocytes -- neutrophils, basophils, and eosinophils -- are distinguished by the size and color of their granules. Granulocytes develop from blood-forming cells called myeloblasts to become mature, infection-fighting cells.
Monocytes: These white blood cells, which are related to granulocytes, also are important in protecting the body against bacteria. They start in the bone marrow as blood-forming monoblasts and develop into mature monocytes. After circulating in the bloodstream for about a day, monocytes enter body tissues to become macrophages, which can destroy some germs by surrounding and digesting them. Macrophages also help lymphocytes to recognize germs and start making antibodies to fight them.
Any of the blood-forming or lymphoid cells from the bone marrow can turn into a leukemia cell. Once this change takes place, the leukemia cells fail to go through their normal process of maturing. Leukemia cells may reproduce quickly, but in most cases the problem is that they don't die when they should. They survive and build up in the bone marrow. Over time, these cells spill into the bloodstream and spread to other organs, where they can keep other cells in the body from functioning normally.
Types of leukemia
Not all leukemias are the same. Leukemias are divided into 4 main types. Knowing the specific type of leukemia helps doctors better predict each patient's prognosis (outlook) and select the best treatment.
Acute leukemia versus chronic leukemia
The first factor in classifying a patient's leukemia is whether most of the abnormal cells are mature (look like normal white blood cells) or immature (look more like stem cells).
In acute leukemia, the bone marrow cells cannot mature properly. Immature leukemia cells continue to reproduce and build up. Without treatment, most patients with acute leukemia would live only a few months. Some types of acute leukemia respond well to treatment, and many patients can be cured. Other types of acute leukemia have a less favorable outlook.
In chronic leukemia, the cells can mature partly but not completely. These cells may look fairly normal but they are not. They generally do not fight infection as well as do normal white blood cells. And they survive longer, build up, and crowd out normal cells. Chronic leukemias tend to progress over a longer period of time, and most patients can live for many years. But chronic leukemias are generally harder to cure than acute leukemias.
Myeloid leukemia versus lymphocytic leukemia
The second factor in classifying leukemia is the type of bone marrow cells that are affected.
Leukemias that start in early forms of myeloid cells -- white blood cells (other than lymphocytes), red blood cells, or platelet-making cells (megakaryocytes) -- are myeloid leukemias (also known as myelocytic, myelogenous, or non-lymphocytic leukemias).
If the cancer starts in early forms of lymphocytes, it is called lymphocytic leukemia (also known as lymphoid or lymphoblastic leukemia). Lymphomas are also cancers that start in lymphocytes. But whereas lymphocytic leukemias develop from cells in the bone marrow, lymphomas develop from cells in lymph nodes or other organs.
By considering whether leukemias are acute or chronic and whether they are myeloid or lymphocytic, they can be divided into 4 main types:
Acute myeloid (or myelogenous) leukemia (AML)
Chronic myeloid (or myelogenous) leukemia (CML)
Acute lymphocytic (or lymphoblastic) leukemia (ALL)
Chronic lymphocytic leukemia (CLL)
What are the risk factors for acute myeloid leukemia?
A risk factor is something that affects your chance of getting a disease, such as cancer. For example, exposing skin to strong sunlight is a risk factor for skin cancer. Smoking is a risk factor for a number of cancers.
But risk factors don't tell us everything. Having a risk factor, or even several risk factors, does not mean that you definitely will get the disease. And many people who get the disease may not have had any known risk factors. Even if a person has a risk factor and develops cancer, it is often very hard to know how much that risk factor may have contributed to the cancer.
There are a few known risk factors for acute myeloid leukemia (AML).
Smoking: The only proven lifestyle-related risk factor for AML is smoking. Many people know that smoking is linked to cancers of the lungs, mouth, throat, and larynx (voice box), but few realize that it can also affect cells that don't come into direct contact with smoke. Cancer-causing substances in tobacco smoke are absorbed by the lungs and spread through the bloodstream to many parts of the body.
Certain chemical exposures: The risk of AML may be increased by exposure to certain chemicals. Long-term exposure to high levels of benzene is a risk factor for AML. Benzene is a solvent used in the rubber industry, oil refineries, chemical plants, shoe manufacturing, and gasoline related industries, and is also present in cigarette smoke, and some glues, cleaning products, detergents, art supplies, and paint strippers.
Some studies have linked heavy workplace formaldehyde exposure to AML risk, but this link was not seen in other studies.
Patients with other cancers who are treated with certain chemotherapy drugs are more likely to develop AML. Some of the drugs linked with these secondary (treatment-related) leukemias include mechlorethamine, procarbazine, chlorambucil, melphalan, etoposide, teniposide and cyclophosphamide. Combining these drugs with radiation therapy further increases the risk.
Most secondary cases of AML occur within 10 years after treatment of Hodgkin disease, non-Hodgkin lymphoma, or childhood acute lymphocytic leukemia (ALL). Secondary leukemias also sometimes occur after treatment of breast, ovarian, or other cancers.
Radiation exposure: High-dose radiation exposure (such as being a survivor of an atomic bomb blast or nuclear reactor accident) increases the risk of developing AML. Japanese atomic bomb survivors had a greatly increased risk of developing acute leukemia, usually within 6 to 8 years after exposure.
The possible risks of leukemia from exposure to lower levels of radiation, such as from radiation therapy, x-rays, or CT scans, are not well-defined. If a fetus is exposed to radiation within the first months of development, it may carry an increased risk of leukemia, but the extent of the risk is not clear. If there is an increased risk it is likely to be small, but to be safe, most doctors try to limit a person's exposure to radiation as much as possible.
Certain blood disorders: Patients with certain blood disorders seem to be at increased risk for getting AML. These include chronicmyeloproliferative disorders such as polycythemia vera, essential thrombocytopenia, and idiopathic myelofibrosis. Chronic myelogenous leukemia (CML) is another type of myeloproliferative disorder, and some patients with CML later develop a form of AML. The risk of developing AML is increased further if treatment for these disorders includes some types of chemotherapy or radiation.
Some patients who have a myelodysplastic syndrome (a pre-leukemic condition) may develop AML. These conditions cause defects in blood cell formation, and over a period of years may evolve into leukemia. Patients who have a myelodysplastic syndrome and develop AML typically have a poor prognosis.
Congenital syndromes (present at birth): For the most part, acute myeloid leukemia does not appear to be an inherited disease. It is rare for it to run in families, so a person's risk is not usually increased if a family member has the disease. But there are some congenital syndromes with genetic changes that seem to raise the risk of AML. These include:
Having an identical twin with AML: This risk is largely confined to the first year of life. As mentioned above, most cases of AML are not thought to have a strong genetic link. Many doctors feel the increased risk among identical twins may be due to leukemia cells being passed from one fetus to the other while still in the womb.
Gender: AML is more common in males than in females, but the reasons for this are not clear.
Uncertain, unproven or controversial risk factors
Other factors that have been studied for a possible link to AML include:
Exposure to electromagnetic fields (such as living near power lines)
Workplace exposure to diesel, gasoline, and certain other chemicals and solvents
Exposure to herbicides or pesticides
Do we know what causes acute myeloid leukemia?
Some people with acute myeloid leukemia (AML) have one or more known risk factors, but most do not. The cause of their cancer remains unknown at this time. Even when a person has one or more risk factors, there is no way to tell whether it actually caused the cancer.
During the past few years, scientists have made great progress in understanding how certain changes in DNA can cause normal bone marrow cells to become leukemia cells. Normal human cells grow and function based mainly on the information contained in each cell's chromosomes. Chromosomes are long molecules of DNA in each cell. DNA is the chemical that makes up our genes -- the instructions for how our cells function. We resemble our parents because they are the source of our DNA. But our genes affect more than the way we look.
Some genes contain instructions for controlling when our cells grow and divide. Certain genes that promote cell division are called oncogenes. Others that slow down cell division or cause cells to die at the right time are calledtumor suppressor genes.
Each time a cell prepares to divide into 2 new cells, it must make a new copy of the DNA in its chromosomes. This process is not perfect, and errors can occur that may affect genes within the DNA. Cancers can be caused by DNA mutations (changes) that turn on oncogenes or turn off tumor suppressor genes. For instance, changes in certain genes such as FLT3, c-KIT, and RAS are commonly found in AML cells.
Mutations in a single gene are found in many cases of AML, but larger changes in one or more chromosomes are also common. Even though these changes involve larger pieces of DNA, their effects are still likely due to changes in just one or a few genes. Several types of chromosome changes may be found in AML cells:
Translocations are the most common type of DNA change that can lead to leukemia. A translocation means that a part of one chromosome breaks off and becomes attached to a different chromosome. The point at which the break occurs can affect nearby genes -- for example, it can turn on oncogenes or turn off genes that would normally help a cell to mature.
Deletions occur when part of a chromosome is lost. This may result in the cell losing a gene that helped keep its growth in check (a tumor suppressor gene).
Inversions occur when part of a chromosome gets turned around, so it is now in reverse order. This can result in the loss of a gene (or genes) because the cell can no longer read its instructions (much like trying to read a book backwards).
Addition means that there is an extra chromosome or part of a chromosome. This can lead to too many copies of certain genes within the cell. This can be a problem if one or more of these genes are oncogenes.
Doctors are trying to figure out why these changes occur and how each of them might lead to leukemia. Not all cases of AML have the same chromosome changes. Some changes are more common than others, and some seem to have more of an effect on a person's prognosis (outlook) than others. For instance, they may affect how quickly the leukemia cells grow, or how likely they are to respond to treatment.
Some people with certain types of cancer have inherited DNA mutations from a parent. These changes increase their risk for the disease. But AML is very rarely caused by one of these inherited mutations.
Most DNA mutations related to AML occur during a person's lifetime, rather than having been inherited before birth. They may result from exposure to radiation or cancer-causing chemicals, but in most cases the reason they occur is not known.
Can acute myeloid leukemia be prevented?
It's not known what causes most cases of acute myeloid leukemia (AML). Since most leukemia patients have no known risk factors, at the present time there is no way to prevent it from developing.
Smoking is by far the most significant controllable risk factor for AML, and quitting offers the greatest chance to reduce a person's risk of AML. Of course, non-smokers are also much less likely than smokers to develop many other cancers, as well as heart disease, stroke, and some other diseases.
Treating some other cancers with chemotherapy and radiation may cause secondary (post-treatment) leukemias. Doctors are trying to figure out how to treat these cancers without raising the risk of developing secondary leukemia. But for now, the obvious benefits of treating life-threatening cancers with chemotherapy and radiation therapy must be balanced against the small chance of getting leukemia years later.
Avoiding known cancer-causing chemicals, such as benzene, can lower the risk of getting AML. But most experts agree that exposure to workplace and environmental chemicals accounts for only a small portion of leukemia cases.
Can acute myeloid leukemia be found early?
For many types of cancers, diagnosis at the earliest possible stage makes treatment much more effective. The American Cancer Society recommends screening tests for early diagnosis of certain cancers in people without any symptoms.
But at this time, there are no special tests recommended to detect acute myeloid leukemia (AML) early. The best way to find leukemia early is to report any possible symptoms of leukemia to the doctor right away.
Some people are known to be at increased risk of AML because of certain blood disorders (such as myelodysplastic syndrome) or inherited disorders (such as Down syndrome), or because they were treated with certain chemotherapy drugs or radiation. Most doctors recommend that these people receive careful, regular medical checkups. They do not usually develop leukemia, but they and their doctors should be familiar with possible symptoms of AML.
How is acute myeloid leukemia diagnosed?
Certain signs and symptoms might suggest that a person may have acute myeloid leukemia (AML), but tests are needed to confirm the diagnosis.
Signs and symptoms of acute myeloid leukemia
Acute myeloid leukemia (AML) can cause many different signs and symptoms. Some occur more commonly with certain subtypes.
Patients with AML often have several non-specific (generalized) symptoms. These can include weight loss, fatigue, fever, night sweats, and loss of appetite. Of course, these are not specific to AML, and more often are caused by something other than leukemia.
Problems caused by low blood cells
Most signs and symptoms of AML result from a shortage of normal blood cells, which happens when the leukemia cells crowd out the normal blood-making cells in the bone marrow. As a result, people do not have enough normal red blood cells, white blood cells, and blood platelets. These shortages show up on blood tests, but they can also cause symptoms.
Anemia is a shortage of red blood cells. It can cause a person to feel tired, weak, cold, dizzy, or lightheaded, and can cause headaches and shortness of breath.
A shortage of normal white blood cells (leukopenia) increases the risk of infections. A common term you may hear is neutropenia, which refers specifically to low levels of neutrophils (a type of granulocyte). Patients with AML may have high white blood cell counts due to excess numbers of leukemia cells, but these cells do not protect against infection the way normal white blood cells do. Fevers and recurring infections are some of the most common symptoms of AML.
A shortage of blood platelets (thrombocytopenia) can lead to excess bruising, bleeding, frequent or severe nosebleeds, and bleeding gums.
Symptoms caused by high numbers of leukemia cells
The cancer cells in AML (blasts) are bigger than normal white blood cells and have more trouble going through tiny blood vessels. If the blast count gets very high, these cells clog up blood vessels and make it hard for normal red blood cells (and oxygen) to get to tissues. This is called leukostasis. Some of the symptoms are like what is seen with a stroke, and include headache, weakness in one side of the body, slurred speech, confusion, and sleepiness. When blood vessels in the lung are affected, patients have problems with shortness of breath. Blood vessels in the eye can be affected as well, leading to blurry vision or even loss of vision. Leukostasis is rare, but it is a medical emergency that needs to be treated right away.
Bleeding and clotting
Patients with a certain type of AML called acute promyelocytic leukemia (APL) may come in with problems with bleeding and clotting. They may have a nose bleed that won’t stop, or a cut that won’t stop oozing. They may also have calf swelling from a blood clot called a deep venous thrombosis (DVT) or chest pain and shortness of breath from a blood clot in the lung (called a pulmonary embolism or PE).
Bone or joint pain
Some patients have bone pain or joint pain caused by the buildup of leukemia cells in these areas.
Swelling in the abdomen
Leukemia cells may collect in the liver and spleen, causing them to enlarge. This may be noticed as a fullness or swelling of the belly. The lower ribs usually cover these organs, but when they are enlarged the doctor can feel them.
Spread to the skin
If leukemia cells spread to the skin, they can cause lumps or spots that may look like common rashes. A tumor-like collection of AML cells under the skin or other parts of the body is called a chloroma or granulocytic sarcoma.
Spread to the gums
Certain types of AML may spread to the gums, causing swelling, pain, and bleeding.
Spread to other organs
Sometimes, leukemia cells may spread to other organs. Spread to central nervous system (brain and spinal cord) can cause headaches, weakness, seizures, vomiting, trouble with balance, facial numbness, or blurred vision. On rare occasions AML may spread to the eyes, testicles, kidneys, or other organs.
Enlarged lymph nodes
In rare cases, AML may spread to lymph nodes. Affected nodes in the neck, groin, underarm areas, or above the collarbone may be felt as lumps under the skin.
Although the symptoms and signs above may be caused by AML, they can also be caused by other conditions. Still, if you have any of these problems, it's important to see your doctor right away so the cause can be found and treated, if needed.
Medical history and physical exam
If signs or symptoms suggest the possibility of leukemia, the doctor will want to obtain a thorough medical history, including how long symptoms have been present and whether or not there is any history of exposure to risk factors.
During the physical exam, the doctor will likely pay close attention to the eyes, mouth, skin, lymph nodes, liver and spleen, and the nervous system, and will look for areas of bleeding or bruising, or possible signs of infection.
If there is reason to think there might be problems caused by abnormal blood cells (anemia, infections, bleeding or bruising, etc.), your doctor will test your blood counts. If the results suggest leukemia may be the cause, the doctor may refer you to a cancer doctor, who may run one or more of the tests described below.
Types of samples used to test for acute myeloid leukemia
If signs and symptoms and/or the results of the physical exam suggest you may have leukemia, the doctor will need to check samples of cells from the blood and bone marrow to be sure of the diagnosis. Other tissue and cell samples may also be taken in order to help guide treatment.
Blood samples for tests for AML are generally taken from a vein in the arm.
Bone marrow samples
Bone marrow samples are obtained from 2 tests that are usually done at the same time:
Bone marrow aspiration
Bone marrow biopsy
The samples are usually taken from the back of the pelvic (hip) bone. but sometimes other bones are used instead. If only an aspiration is to be done, it may be taken from the sternum (breast bone).
In bone marrow aspiration, you lie on a table (either on your side or on your belly). The doctor will clean the skin over the hip and then numb the area and the surface of the bone with a local anesthetic. This may cause a brief stinging or burning sensation. A thin, hollow needle is then inserted into the bone and a syringe is used to suck out a small amount of liquid bone marrow (about 1 teaspoon). Even with the anesthetic, most patients still have some brief pain when the marrow is removed.
A bone marrow biopsy is usually done just after the aspiration. A small piece of bone and marrow (about 1/16 inch in diameter and 1/2 inch long) is removed with a slightly larger needle that is twisted as it is pushed down into the bone. This causes a pressure feeling, and rarely may also cause some brief pain. Once the biopsy is done, pressure will be applied to the site to help prevent bleeding.
These bone marrow tests are used to help diagnose leukemia. They may also be repeated later to tell if the leukemia is responding to treatment.
The cerebrospinal fluid (CSF) is the liquid that surrounds the brain and spinal cord. Leukemia can spread to the area around the brain and spinal cord. To check for this spread, doctors remove a sample of CSF for testing. The procedure used to remove a sample of this fluid is called a lumbar puncture (spinal tap).
For this test, the patient may lie on his side or sit up. The doctor first numbs an area in the lower part of the back over the spine. A small, hollow needle is then placed between the bones of the spine to withdraw some of the fluid.
A lumbar puncture is not often used to test for AML, unless the patient is having symptoms that could be caused by the spread of leukemia cells into the central nervous system (CNS).
A lumbar puncture is sometimes used to deliver chemotherapy drugs into the CSF to prevent or treat the spread of leukemia to the spinal cord and brain.
Lab tests used to diagnose and classify acute myeloid leukemia
One or more of the following lab tests may be done on the samples to diagnose AML and/or to determine the specific subtype of AML.
Complete blood count and peripheral blood smear
The complete blood count (CBC) is a test that measures the different cells in the blood, such as the red blood cells, the white blood cells, and the platelets. This test is often done along with a differential (or diff) which looks at the numbers of the different types of white blood cells. For the peripheral blood smear, a sample of blood is looked at under the microscope. These tests look at how the different types of cells in the blood appear under the microscope and how many of them there are. Changes in the numbers and the appearance of these cells often help diagnose leukemia.
Most patients with AML have too many immature white cells in their blood, and not enough red blood cells or platelets. Many of the white blood cells may be myeloblasts ("blasts"), which are immature blood-forming cells that are not normally found in the bloodstream. These immature cells do not function like normal, mature white blood cells. These findings may suggest leukemia, but the disease usually is not diagnosed without looking at a sample of bone marrow cells.
Blood chemistry and coagulation tests
These tests measure the amounts of certain chemicals and the ability of the blood to clot. These tests are not used to diagnose leukemia, but they can help detect liver or kidney problems, abnormal levels of certain minerals in the blood, or problems with the clotting ability of the blood.
Routine microscopic exams
Samples of blood, bone marrow, or CSF are looked at under a microscope by a pathologist (a doctor specializing in lab tests) and may be reviewed by the patient's hematologist/oncologist (a doctor specializing in cancer and blood diseases).
The doctors will look at the size, shape, and other traits of the white blood cells in the samples to classify them into specific types.
A key element is whether the cells look mature (like normal blood cells) or immature (lacking features of normal blood cells). The most immature cells are called myeloblasts (or "blasts" for short).
The percentage of cells in the bone marrow or blood that are blasts is particularly important. Having at least 20% blasts in the marrow or blood is generally required for a diagnosis of AML. It can also be diagnosed if the blasts have a chromosome change that occurs only in a specific type of AML, even if the blast percentage doesn't reach 20%. Sometimes the blasts look similar to normal immature cells in the bone marrow. But in normal bone marrow, the blast count is 5% or less. In order for a patient to be considered to be in remission after treatment, the blast percentage in the bone marrow must be no higher than 5%.
Sometimes just counting and looking at the cells does not provide a clear diagnosis. Additional tests may be used to confirm the diagnosis of AML.
For cytochemistry tests, cells are exposed to chemical stains (dyes) that react with only some types of leukemia cells. These stains cause color changes that can be seen under a microscope, which can help the doctor determine what types of cells are present. For instance, one stain can help distinguish AML cells from acute lymphocytic leukemia (ALL) cells. The stain causes the granules of most AML cells to appear as black spots under the microscope, but it does not cause ALL cells to change colors.
Flow cytometry and immunohistochemistry
Flow cytometry is often used to look at the cells from bone marrow and blood samples. It is very helpful in determining the exact type of leukemia.
The test looks for certain substances on the surface of cells that help identify what types of cells they are. A sample of cells is treated with special antibodies (man-made immune system proteins) that stick to the cells only if these substances are present on their surfaces. The cells are then passed in front of a laser beam. If the cells now have antibodies attached to them, the laser will cause them to give off light, which can be measured and analyzed by a computer. Groups of cells can be separated and counted by these methods.
In immunohistochemistry tests, cells from the blood or bone marrow samples are also treated with special antibodies. But instead of using a laser and computer, the sample is treated so that certain types of cells change color when seen under a microscope.
These tests are used for immunophenotyping -- classifying leukemia cells according to the substances (antigens) on their surfaces. Specific types of leukemia cells have different antigens depending on their cell of origin and how mature they are, and this information can be helpful in AML classification.
For this test, a cell's chromosomes (long strands of DNA) are looked at under a microscope. Normal human cells contain 23 pairs of chromosomes, each of which are a certain size and stain a certain way. In some cases of AML, the cells have chromosome changes that can be seen under a microscope.
For instance, 2 chromosomes may swap some of their DNA, so that part of one chromosome becomes attached to part of a different chromosome. This change, called a translocation, can usually be seen under a microscope. Other changes in chromosomes are also possible (see below). Recognizing these changes can help identify certain types of AML and may be important in determining the outlook for the patient.
This test usually takes about 2 to 3 weeks because the leukemia cells must grow in lab dishes for a couple of weeks before their chromosomes are ready to be looked at under the microscope.
The results of cytogenetic testing are written in a shorthand form that describes which chromosome changes are present.
A translocation, written as t(8;21), for example, means a part of chromosome 8 is now located on chromosome 21, and vice versa.
An inversion, written as inv(16), for example, means that part of the chromosome 16 is upside down and is now in reverse order but is still attached to the chromosome it originated from.
A deletion, written as del(7) or -7, for example, indicates part of chromosome 7 has been lost.
An addition, +8, for example, means that all or part of chromosome 8 has been duplicated, and too many copies of it are found within the cell.
Not all chromosome changes can be seen under a microscope. Other lab tests can often detect these changes.
Fluorescent in situ hybridization (FISH)
This is similar to cytogenetic testing. It uses special fluorescent dyes that only attach to specific parts of particular chromosomes. FISH can find the chromosome changes (such as translocations) that are visible under a microscope in standard cytogenetic tests, as well as some changes too small to be seen with usual cytogenetic testing.
FISH can be used to look for specific changes in chromosomes. It can be used on regular blood or bone marrow samples. It is very accurate and can usually provide results within a couple of days, which is why this test is now used in many medical centers.
Polymerase chain reaction (PCR)
This is a very sensitive DNA test that can also find some chromosome changes too small to be seen under a microscope, even if very few leukemia cells are present in a sample.
These tests may also be used after treatment to find small numbers of leukemia cells that may not be visible under a microscope.
Imaging tests for acute myeloid leukemia
Imaging tests use x-rays, sound waves, magnetic fields, or radioactive particles to create pictures of the inside of the body. Leukemia does not usually form visible tumors, so imaging tests are of limited value. There are several imaging tests that might be done in people with AML, but they are done more often to look for infections or other problems, rather than to look for the leukemia itself. In some cases imaging tests may be done to help determine the extent of the disease, if it is thought it may have spread beyond the bone marrow and blood.
Routine chest x-rays may be done if a lung infection is suspected.
Computed tomography (CT) scan
The CT scan is a type of x-ray that produces detailed, cross-sectional images of your body. Unlike a regular x-ray, CT scans can show the detail in soft tissues (such as internal organs).
This test can help tell if any lymph nodes or organs in your body are enlarged. It isn't usually needed to diagnose AML, but it may be done if your doctor suspects the leukemia is growing in an organ, like your spleen.
Instead of taking one picture, like a regular x-ray, a CT scanner takes many pictures as it rotates around you. A computer then combines these pictures into detailed images of the part of your body that is being studied.
Before the scan, you may be asked to drink a contrast solution and/or get an intravenous (IV) injection of a contrast dye that helps better outline abnormal areas in the body. You may need an IV line through which the contrast dye is injected. Injecting contrast dye can cause a feeling of flushing or warmth, in the face or elsewhere. Some people get hives or, rarely, more serious allergic reactions like trouble breathing and low blood pressure. Be sure to tell the doctor if you have ever had a reaction to any contrast material used for x-rays.
CT scans take longer than regular x-rays. You need to lie still on a table while they are being done. During the test, the table moves in and out of the scanner, a ring-shaped machine that completely surrounds the table. You might feel a bit confined by the ring you have to lie in when the pictures are being taken.
In some cases, a CT can be used to guide a biopsy needle precisely into a suspected abnormality, such as an abscess. For this procedure, called a CT-guided needle biopsy, you remain on the CT scanning table while a radiologist moves a biopsy needle through the skin and toward the location of the mass. CT scans are repeated until the needle is within the mass. A sample is then removed to be looked at under a microscope.
PET/CT: Some machines combine the CT scan with a PET scan (PET/CT scan). For a PET scan, glucose (a form of sugar) containing a radioactive atom is injected into the blood. Because cancer cells in the body grow rapidly, they absorb large amounts of the radioactive sugar. A special camera can then create a picture of areas of radioactivity in the body. The PET/CT scan allows the doctor to compare areas of higher radioactivity on the PET scan with the more detailed appearance of that area on the CT.
Magnetic resonance imaging (MRI) scan
Like CT scans, MRI scans provide detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. The energy from the radio waves is absorbed by the body and then released in a pattern formed by the type of body tissue and by certain diseases. A computer translates the pattern into a very detailed image of parts of the body. A contrast material called gadolinium is often injected into a vein before the scan to better see details. The contrast material usually does not cause allergic reactions.
MRI scans are very helpful in looking at the brain and spinal cord, but they are not often needed in people with AML.
MRI scans take longer than CT scans -- often up to an hour. You may have to lie inside a narrow tube, which is confining and can be distressing to some people. Newer, more open MRI machines may be another option. The MRI machine makes loud buzzing and clicking noises that you may find disturbing. Some places provide headphones or earplugs to help block this out.
Ultrasound uses sound waves and their echoes to produce a picture of internal organs or masses. Most often for this test, a small, microphone-like instrument called a transducer is placed on the skin over the area to be examined (the skin is first lubricated with gel). It emits sound waves and picks up the echoes as they bounce off the organs. The echoes are converted by a computer into an image that is displayed on a computer screen.
Ultrasound can be used to look at lymph nodes near the surface of the body or to look for enlarged organs inside your abdomen such as the kidneys, liver, and spleen.
This is an easy test to have done, and it uses no radiation. For most scans, you simply lie on a table, and a technician moves the transducer over the part of your body being looked at.
Gallium scan and bone scan
These tests are not often done for AML, but they may be useful if a patient has bone pain that might be due to either an infection or cancer involving the bones.
For these tests, the radiologist injects a slightly radioactive chemical into the bloodstream, which collects in areas of cancer or infection in the body. These areas can then be viewed with a special type of camera. The images from these scans are seen as "hot spots" in the body, but they don't provide much detail. If an area lights up on the scan, other imaging tests such as x-rays, CTs, or MRIs may be done to get a more detailed look at the area. If leukemia is a possibility, a biopsy of the area may be needed to confirm this.
How is acute myeloid leukemia classified?
Most types of cancers are assigned numbered stages to describe their extent in the body, based on the size of the tumor and how far the cancer has spread.
Acute myeloid leukemia (AML), on the other hand, does not usually form tumor masses. It generally involves all of the bone marrow in the body and, in some cases, may have spread to other organs, such as the liver and spleen. Therefore the outlook for the patient with AML depends on other information, such as the subtype of AML (determined by lab tests), the age of the patient, and other lab test results.
World Health Organization (WHO) classification of AML
The FAB classification system is useful and is still commonly used to group AML into subtypes. But it doesn't take into account many of the factors that are known to impact prognosis (outlook). The World Health Organization (WHO) has proposed a newer system that includes some of these factors to try to help better classify cases of AML based on a patient's outlook. Not all doctors use this new system.
The WHO classification system divides AML into several broad groups:
AML with certain genetic abnormalities
AML with a translocation between chromosomes 8 and 21
AML with a translocation or inversion in chromosome 16
AML with changes in chromosome 11
APL (M3), which usually has translocation between chromosomes 15 and 17
AML with multilineage dysplasia (more than one abnormal myeloid cell type is involved)
AML related to previous chemotherapy or radiation
AML not otherwise specified (includes cases of AML that don't fall into one of the above groups; similar to the FAB classification)
Undifferentiated AML (M0)
AML with minimal maturation (M1)
AML with maturation (M2)
Acute myelomonocytic leukemia (M4)
Acute monocytic leukemia (M5)
Acute erythroid leukemia (M6)
Acute megakaryoblastic leukemia (M7)
Acute basophilic leukemia
Acute panmyelosis with fibrosis
Myeloid sarcoma (also known as granulocytic sarcoma or chloroma)
Undifferentiated or biphenotypic acute leukemias (leukemias that have both lymphocytic and myeloid features). Sometimes called ALL with myeloid markers, AML with lymphoid markers, or mixed lineage leukemias.
Leukemia treatment has improved over the years, so research has focused on why some patients have a better chance to be cured than others. The AML subtype certainly plays a role in this. Other differences among patients that affect response to treatment are called prognostic factors. They help doctors decide if people with a certain type of leukemia should receive more or less treatment.
These prognostic factors include the cytogenetic test results (showing chromosome or gene changes), the patient's age, and the white blood cell count. Other important factors include pre-existing blood disorders (such as a myelodysplastic syndrome) and a history of treatment with chemotherapy and/or radiation therapy for an earlier cancer.
Chromosome changes give one clue to prognosis. Not all patients have these abnormalities. Those listed below are the most common, but there are many others. Patients without any of these usually have an outlook that is between favorable and unfavorable.
Translocation between chromosomes 8 and 21 (seen most often in patients with M2)
Inversion of chromosome 16 (seen most often in patients with M4 eos)
Translocation between chromosomes 15 and 17 (seen most often in patients with M3)
Deletion (loss) of part of chromosome 5 or 7 (no specific AML type)
Complex changes - those involving several chromosomes (no specific AML type)
Newer tests allow doctors to find changes within specific genes on chromosomes. People who have certain gene mutations may have a better or worse outlook.
For instance, about 1 patient out of 3 with AML has a mutation in the FLT3 gene. These people tend to have a poorer outcome, but new drugs that target this abnormal gene are now being studied, which may lead to better outcomes.
On the other hand, people with changes in the NPM1 gene (and no other abnormalities) seem to have a better prognosis than people without this change.
In the coming years, doctors will use newer lab tests to learn more about the underlying genetic defects that cause AML and how they can be used to predict a patient's prognosis. These genetic defects might also form the basis for treating the leukemias.
Older patients (over 60) generally do not fare as well as younger patients. Some of this may be because they are more likely to have unfavorable chromosome abnormalities. Older patients may also have other medical conditions that can make it harder to treat them with more intense chemotherapy regimens.
White blood cell count
A high white blood cell count (>100,000) at the time of diagnosis is linked to a worse outlook.
Prior blood disorders or cancers
Having a prior blood disorder such as a myelodysplastic syndrome or having AML that develops after treatment for another cancer tends to lead to a worse prognosis, as these types of AML are often harder to treat.
Having an active systemic (blood) infection at the time of diagnosis makes a poor outcome more likely.
Leukemia cells in the central nervous system
Leukemia that has spread to the area around the brain and spinal cord can be hard to treat, since most regular chemotherapy drugs don’t penetrate that area.
Status of acute myeloid leukemia after treatment
Not surprisingly, how well a leukemia responds to treatment also has an effect on long-term prognosis.
A remission (complete remission) is usually defined as having no evidence of disease after treatment. This means the bone marrow contains fewer than 5% blast cells, the blood cell counts are within normal limits, and there are no signs or symptoms of the disease. A molecular complete remission means there is no evidence of leukemia cells in the bone marrow, even when using very sensitive tests, such as PCR.
Minimal residual disease is a term used after treatment when leukemia cells can't be found in the bone marrow using standard tests (such as looking at cells under a microscope), but more sensitive tests (such as flow cytometry or PCR) find evidence that leukemia cells remain in the bone marrow.
Active disease means that either there is evidence that the leukemia is still present during treatment or that the disease has come back after treatment (relapsed). For a patient to be in relapse, they must have more than 5% blast cells present in the bone marrow.
Click here to go to the treatment: http://www.cancermedicines.in/treatment.php?id=71