Leukemia--Acute Lymphocytic (ADULTS)

What is cancer?

The body is made up of hundreds of millions of living cells. Normal body cells grow, divide, and die in an orderly fashion. During the early years of a person's life, normal cells divide faster to allow the person to grow. After the person becomes an adult, most cells divide only to replace worn-out or dying cells or to repair injuries.

Cancer begins when cells in a part of the body start to grow out of control. There are many kinds of cancer, but they all start because of out-of-control growth of abnormal cells.

Cancer cell growth is different from normal cell growth. Instead of dying, cancer cells continue to grow and form new, abnormal cells. Cancer cells can also invade (grow into) other tissues, something that normal cells cannot do. Growing out of control and invading other tissues are what makes a cell a cancer cell.

Cells become cancer cells because of damage to DNA. DNA is in every cell and directs all its actions. In a normal cell, when DNA gets damaged the cell either repairs the damage or the cell dies. In cancer cells, the damaged DNA is not repaired, but the cell doesn’t die like it should. Instead, this cell goes on making new cells that the body does not need. These new cells will all have the same damaged DNA as the first cell does.

People can inherit damaged DNA, but most DNA damage is caused by mistakes that happen while the normal cell is reproducing or by something in our environment. Sometimes the cause of the DNA damage is something obvious, like cigarette smoking. But often no clear cause is found.

In most cases the cancer cells form a tumor. Some cancers, like leukemia, rarely form tumors. Instead, these cancer cells involve the blood and blood-forming organs and circulate through other tissues where they grow.

Cancer cells often travel to other parts of the body, where they begin to grow and form new tumors that replace normal tissue. This process is called metastasis. It happens when the cancer cells get into the bloodstream or lymph vessels of our body.

No matter where a cancer may spread, it is always named for the place where it started. For example, breast cancer that has spread to the liver is still called breast cancer, not liver cancer. Likewise, prostate cancer that has spread to the bone is metastatic prostate cancer, not bone cancer.

Different types of cancer can behave very differently. For example, lung cancer and breast cancer are very different diseases. They grow at different rates and respond to different treatments. That is why people with cancer need treatment that is aimed at their particular kind of cancer.

Not all tumors are cancerous. Tumors that aren't cancer are called benign. Benign tumors can cause problems – they can grow very large and press on healthy organs and tissues. But they cannot grow into (invade) other tissues. Because they can’t invade, they also can’t spread to other parts of the body (metastasize). These tumors are almost never life threatening.

What is acute lymphocytic leukemia?

Acute lymphocytic leukemia (ALL), also called acute lymphoblastic leukemia, is a cancer that starts from white blood cells called lymphocytes in the bone marrow (the soft inner part of the bones, where new blood cells are made).

In most cases, the leukemia invades the blood fairly quickly. It can then 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 that start in these organs and then spread to the bone marrow are not leukemia.

The term "acute" means that the leukemia can progress quickly, and if not treated, would probably be fatal in a few months. "Lymphocytic" or "lymphoblastic" means it develops from cells that were destined to become certain cells called lymphocytes or lymphoblasts. This is different from acute myeloid leukemia (AML), which develops in other blood cell types found in the bone marrow. For more information on AML, see our document, Leukemia--Acute Myeloid.

Other types of cancer that start in lymphocytes are known as lymphomas (non-Hodgkin lymphoma or Hodgkin disease). The main difference between these types of cancers is that ALL starts in the bone marrow and may spread to other places, while lymphomas start in lymph nodes or other organs and then may spread to the bone marrow. Sometimes cancerous lymphocytes are found in both the bone marrow and lymph nodes when the cancer is first diagnosed, which can make it hard to tell if the cancer is a leukemia or a lymphoma. If more than 25% of the bone marrow is replaced by cancerous lymphocytes, the disease is usually considered to be a leukemia. The size of lymph nodes is also important. The bigger they are, the more likely the disease is a lymphoma. For more information on lymphomas, see our documents, Non-Hodgkin Lymphoma and Hodgkin Disease.

Normal bone marrow, blood, and lymphoid tissue

In order to understand the different types of leukemia, it helps to know about the blood and lymph systems.

Bone marrow

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. These 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)
• Platelets

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

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 B lymphocytes (B cells) and T lymphocytes (T cells).

• B lymphocytes: 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 called granulocytes to recognize and destroy them.
• T lymphocytes: 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. Neutrophils are the most common type of granulocyte and are essential in fighting infection from bacteria.

Monocytes

These white blood cells, which are related to granulocytes, also help protect 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 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 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).

Acute leukemia: 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.

Chronic leukemia: 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.

Myeloid leukemia: 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).

Lymphocytic leukemia: 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. In lymphocytic leukemias the cancer cells tend to build up in the bone marrow, while in lymphomas lymph nodes or other organs tend to be more affected.

Leukemias can be divided into 4 main types based on whether they are acute or chronic, and whether they are myeloid or lymphocytic. The 4 main types are:

• Acute myeloid (or myelogenous) leukemia (AML)
• Chronic myeloid (or myelogenous) leukemia (CML)
• Acute lymphocytic (or lymphoblastic) leukemia (ALL)
• Chronic lymphocytic leukemia (CLL)

ALL is the most common of the 4 major types of leukemia among children, but it is actually the least common type among adults.

The rest of this document focuses on acute lymphocytic leukemia (ALL) in adults. For information on ALL in children, please see our document, Childhood Leukemias. Chronic leukemias and acute myeloid leukemia of adults are discussed in other American Cancer Society documents.

What are the key statistics about acute lymphocytic leukemia?

The American Cancer Society's estimates for leukemia in the United States for 2010 are:

• About 43,050 new cases of leukemia (all kinds) and 21,840 deaths from leukemia (all kinds)
• About 5,330 new cases of acute lymphocytic leukemia (ALL), of which about 1 out of 3 will be in adults
• About 1,420 deaths from ALL, about 3 out of 4 which will be in adults

The risk for developing ALL is highest in children between 2 and 4 years of age. The risk then declines slowly until the mid-20s, and begins to rise again slowly after age 50.

The average person's lifetime risk of getting ALL is about 1/10 of 1% (about 1 in 1,000). The risk is slightly higher in men than in women, and higher in whites than in African Americans.

Some information on treatment success rates for adult ALL can be found in the section, "How is acute lymphocytic leukemia treated?"

What are the risk factors for acute lymphocytic 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 only a few known risk factors for acute lymphocytic leukemia (ALL).

Radiation exposure

Exposure to high levels of radiation is a risk factor for both types of acute leukemia (ALL and acute myeloid leukemia, or 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, is not well-defined. Exposure of a fetus to radiation within the first months of development 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 chemical exposures

The risk of ALL may be increased by exposure to certain chemotherapy drugs and certain chemicals, including benzene. 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. Chemical exposure is more strongly linked to an increased risk of AML than to ALL.

Certain viral infections

Infection with the human T-cell lymphoma/leukemia virus-1 (HTLV-1) can cause a rare type of T-cell acute lymphocytic leukemia. Most cases occur in Japan and the Caribbean area. This disease is not common in the United States.

Epstein-Barr virus (EBV) most often causes infectious mononucleosis ("mono") in the United States. In Africa, the virus has been linked to Burkitt lymphoma, as well as to a form of acute lymphocytic leukemia.

Inherited syndromes

Acute lymphocytic leukemia does not appear to be an inherited disease. It does not seem to run in families, so a person's risk is not increased if a family member has the disease. But there are some inherited syndromes with genetic changes that seem to raise the risk of ALL. These include:

• Down syndrome
• Klinefelter syndrome
• Fanconi anemia
• Bloom syndrome
• Ataxia-telangiectasia
• Neurofibromatosis

Race/ethnicity

ALL is more common in whites than in African Americans, but the reasons for this are not clear.

Gender

ALL is slightly more common in males than in females. The reason for this is unknown.

Having an identical twin with ALL

This risk is largely confined to the first year of life. As mentioned earlier, most cases of ALL 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.

Uncertain, unproven or controversial risk factors

Other factors that have been studied for a possible link to ALL include:

• Exposure to electromagnetic fields (such as living near power lines)
• Workplace exposure to diesel, gasoline, pesticides, and certain other chemicals
• Smoking
• Exposure to hair dyes

So far, none of these factors has been linked conclusively to ALL. Research in these areas continues

Do we know what causes acute lymphocytic leukemia?

Some people with acute lymphocytic leukemia (ALL) have one or more of the known risk factors (see the section, "What are the risk factors for acute lymphocytic leukemia?"), 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 called tumor 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.

Translocations are the most common type of DNA abnormality that can lead to leukemia. Human DNA is packaged in 23 pairs of chromosomes. A translocation means that DNA from one chromosome breaks off and becomes attached to a different chromosome. The point at which the break occurs can affect genes -- for example, it can turn on oncogenes or turn off genes that would normally help a cell to mature.

The most common translocation in ALL in adults is known as the Philadelphia chromosome, which is a swapping of DNA (translocation) between chromosomes 9 and 22, abbreviated as t(9;22). It occurs in about 25% to 30% of adult ALL cases. Other, less common translocations are those between chromosomes 4 and 11, abbreviated as t(4;11), or 8 and 14, abbreviated as t(8;14).

Other chromosome changes such as deletions (the loss of part of a chromosome) and inversions (the rearrangement of the DNA within part of a chromosome) can also affect the development of ALL, although they are less common. In many cases of ALL, the gene changes that lead to the leukemia are not known.

Doctors are trying to figure out why these changes occur and how each of them might lead to leukemia. Not all cases of ALL 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.

Some people with certain types of cancer have inherited DNA mutations from a parent. These changes increase their risk for the disease. But ALL is very rarely caused by one of these inherited mutations.

Usually DNA mutations related to ALL occur during the 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 lymphocytic leukemia be prevented?

Many types of cancer can be prevented by lifestyle changes to avoid certain risk factors, but there is no known way to prevent most cases of leukemia at this time. Most acute lymphocytic leukemia patients have no known risk factors, so there is no way to prevent these leukemias from developing.

Can acute lymphocytic 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 lymphocytic leukemia (ALL) early. The best way to find leukemia early is to report any possible signs or symptoms of leukemia (see the section, "How is acute lymphocytic leukemia diagnosed?") to the doctor right away.

Some people are known to be at increased risk of developing ALL because of an inherited disorder such as Down syndrome. Most doctors recommend that these people have careful, regular medical checkups. The development of leukemia in people with these syndromes, although greater than in the general population, is still very rare.

How is acute lymphocytic leukemia diagnosed?

Certain signs and symptoms might suggest that a person may have acute lymphocytic leukemia (ALL), but tests are needed to confirm the diagnosis.

Signs and symptoms of acute lymphocytic leukemia

Acute lymphocytic leukemia (ALL) can cause many different signs and symptoms. Most of these occur in all kinds of ALL, but some are more common with certain subtypes.

Generalized symptoms

Patients with ALL often have several non-specific symptoms. These can include weight loss, fever, night sweats, fatigue, and loss of appetite. Of course, these are not just symptoms of ALL and are more often caused by something other than leukemia.

Problems caused by low blood cell counts

Most signs and symptoms of ALL 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, dizzy, cold, lightheaded, or short 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 ALL 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 ALL.
• A shortage of blood platelets (thrombocytopenia) can lead to excess bruising, bleeding, frequent or severe nosebleeds, and bleeding gums.

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.

Enlarged lymph nodes

Acute lymphocytic leukemia may spread to lymph nodes. If the affected nodes are close to the surface of the body (on the sides of the neck, in the groin, in underarm areas, above the collarbone, etc.), they may be noticed as lumps under the skin. Lymph nodes inside the chest or abdomen may also swell, but these can be detected only by imaging tests such as computed tomography (CT) or magnetic resonance imaging (MRI) scans.

Spread to other organs

Less often, ALL may spread to other organs. If it spreads to the brain and spinal cord (central nervous system, or CNS) it can cause headaches, weakness, seizures, vomiting, trouble with balance, facial numbness, or blurred vision. ALL may also spread to the chest cavity, where it can cause fluid buildup and trouble breathing. On rare occasions it may spread to the skin, eyes, testicles, kidneys, or other organs.

Bone or joint pain

Some patients have bone pain or joint pain caused by the buildup of leukemia cells near the surface of the bone or inside the joint.

Enlarged thymus gland

The T-cell subtype of ALL often affects the thymus, which is a small gland in the middle of the chest located behind the sternum (breastbone) and in front of the trachea (windpipe). An enlarged thymus can press on the trachea, causing coughing or trouble breathing.

The superior vena cava (SVC), a large vein that carries blood from the head and arms back to the heart, passes next to the thymus. Growth of the thymus due to excess leukemia cells may press on the SVC, causing the blood to "back up" in the veins. This is known as SVC syndrome. It can cause swelling in the face, neck, arms, and upper chest (sometimes with a bluish-red color). It can also cause headaches, dizziness, and a change in consciousness if it affects the brain. The SVC syndrome can be life-threatening, and needs to be treated right away.

Medical history and physical exam

If any signs and symptoms suggest the possibility of leukemia, the doctor will want to get 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 probably focus on any enlarged lymph nodes, areas of bleeding or bruising, or possible signs of infection. The eyes, mouth, and skin will be looked at carefully, and a thorough nervous system exam will be done. The abdomen will be felt for signs of an enlarged spleen or liver.

If there is reason to think the problems might be caused by abnormal numbers of blood cells (anemia, infections, bleeding or bruising, etc.), the doctor will likely 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 lymphocytic 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 your blood and bone marrow to be sure of the diagnosis. Other tissue and cell samples may also be taken to help guide treatment.

Blood samples

Blood samples for tests for ALL are generally taken from a vein in the arm.

Bone marrow samples

Bone marrow samples are obtained from a bone marrow aspiration and biopsy -- two tests that are usually done at the same time. The samples are usually taken from the back of the pelvic (hip) bone, although in some cases they may be taken from the sternum (breastbone) or other bones.

In bone marrow aspiration, you lie on a table (either on your side or on your belly). After cleaning the skin over the hip, the doctor numbs the skin and the surface of the bone with local anesthetic, which 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. The biopsy may also briefly cause some 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 done again later to tell if the leukemia is responding to treatment.

Spinal fluid

The cerebrospinal fluid (CSF) is the liquid that surrounds the brain and spinal cord. ALL 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). A lumbar puncture can also be used to put chemotherapy drugs into the CSF to try to prevent or treat the spread of leukemia to the spinal cord and brain.

For this test, the patient may be lying on their side or sitting 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.

Lymph node tissue

Removing a lymph node or part of a lymph node is often an important procedure when diagnosing lymphomas, but is only rarely needed with leukemias.

In this procedure, known as a lymph node biopsy, a surgeon cuts through the skin to remove all or part of a lymph node. If the node is near the skin surface, this is a simple operation that can often be done with local anesthesia, but if the node is inside the chest or abdomen, general anesthesia (where the patient is asleep) is used. When the entire lymph node is removed, it is called an excisional lymph node biopsy. If only part of the lymph node is removed, it is called an incisional lymph node biopsy.

Lab tests used to diagnose and classify acute lymphocytic leukemia

One or more of the following lab tests may be done on the samples to diagnose ALL, to determine what subtype of ALL it is, and/or to help determine how advanced the disease is.

Blood cell counts and blood cell exam (peripheral blood smear)

These tests look at the numbers of the different types of blood cells and at how they look under the microscope. Changes in the numbers and the appearance of these cells often help diagnose leukemia.

Most patients with ALL have too many immature white cells in their blood, and not enough red blood cells or platelets. Many of the white blood cells will be lymphoblasts (blasts), which are immature lymphocytes not normally found in the bloodstream. These immature cells do not function like normal, mature white blood cells. Even though these findings may suggest leukemia, the disease usually is not diagnosed without looking at a sample of bone marrow cells.

Blood chemistry and coagulation tests

Blood chemistry tests measure the amounts of certain chemicals in the blood, but they are not used to diagnose leukemia. In patients already known to have ALL, these tests can help detect liver or kidney problems caused by spreading leukemia cells or the side effects of certain chemotherapy drugs. These tests also help determine if treatment is needed to correct low or high blood levels of certain minerals.

Blood coagulation tests may also be done to make sure the blood is clotting properly.

Routine microscopic exams

Any samples taken (blood, bone marrow, lymph node tissue, 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 appear mature (look like normal blood cells), or immature (lacking features of normal blood cells). The most immature cells are called lymphoblasts (or "blasts" for short).

Determining what percentage of cells in the bone marrow are blasts is particularly important. A diagnosis of ALL generally requires that at least 20% to 30% of the cells in the bone marrow are blasts. Under normal circumstances, blasts are never more than 5% of bone marrow cells.

Sometimes just counting and looking at the cells does not provide a definite diagnosis, and other lab tests are needed.

Cytochemistry

In cytochemistry tests, cells are exposed to chemical stains (dyes) that react only with 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 ALL from acute myeloid leukemia (AML). 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, lymph nodes, 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 versions of 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. Different types of lymphocytes have different antigens on their surface. These antigens also change as each cell matures. Each patient's leukemia cells all have the same antigens because they are all derived from the same cell. Lab testing for antigens is a very sensitive way to diagnose ALL. Because cells from different subtypes of ALL have different sets of antigens, this is sometimes helpful in ALL classification, although it is not needed in most cases.

Cytogenetics

For this test, chromosomes (long strands of DNA) are looked at under a microscope to detect any changes. Normal human cells contain 23 pairs of chromosomes, each of which is a certain size and stains a certain way. In some cases of leukemia, 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. Recognizing these changes can help identify certain types of ALL and may be important in determining the outlook for the patient.

Most of the chromosome changes in adult ALL are translocations. The most common one is a translocation between chromosomes 9 and 22, which results in a shortened chromosome 22 (called the Philadelphia chromosome). About 25% to 30% of adults with ALL have this abnormality in their leukemia cells.

Information about this and other translocations may be useful in predicting response to treatment. For this reason, most doctors will test all patients with ALL for genetic changes in the leukemia cells.

Cytogenetic testing 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 viewed under the microscope.

Not all chromosome changes can be seen under a microscope. Other lab tests can often help find these changes.

Fluorescent in situ hybridization (FISH)

This is another type of chromosome test. It uses special fluorescent dyes that only attach to specific parts of particular chromosomes. FISH can find most 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.

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 try to find small numbers of leukemia cells that may not be visible under a microscope.

Imaging tests

Imaging tests use x-rays, sound waves, magnetic fields, or radioactive particles to produce pictures of the inside of the body. Because leukemia does not usually form visible tumors, imaging tests are of limited value. Imaging tests might be done in people with ALL, but they are done more often to look for infections or other problems, rather than for the leukemia itself. In some cases they 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.

X-rays

Routine chest x-rays may be done if the doctor suspects a lung infection. They may also be done to look for enlarged lymph nodes in the chest.

Computed tomography (CT) scan

The CT scan is a type of x-ray test 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 ALL, but it may be done if your doctor suspects leukemia cells are growing in an organ, like your spleen.

Instead of taking one picture, as does 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. The IV injection of contrast dye can cause a feeling of flushing or warmth in the face or elsewhere. Some people are allergic and get hives or, rarely, more serious 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 lay 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 stay 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 biopsy sample is then removed to be looked at under a microscope.

Sometimes a test is done that combines 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. This contrast material is different than the one used for CT scans.

MRI scans are very helpful in looking at the brain and spinal cord.

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

Ultrasound uses sound waves and their echoes to produce a picture of internal organs or masses. For this test, a small, microphone-like instrument called a transducer is placed on the skin (which is first lubricated with gel). The transducer 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 ultrasounds, 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 ALL, but they may be useful if a patient has bone pain that might be due to either an infection or cancer in the bones.

For these tests, the doctor or nurse 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 lymphocytic 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 lymphocytic leukemia (ALL), on the other hand, does not usually form tumor masses. It generally affects all of the bone marrow in the body and, in many cases, may have spread to other organs, such as the liver, spleen, and lymph nodes. Therefore the outlook for the patient with ALL depends on other information, such as the subtype of ALL (determined by lab tests), the age of the patient, and other lab test results.

Different systems have been used to classify ALL into subtypes.

The French-American-British (FAB) classification

In the 1970s, a group of French, American, and British (FAB) leukemia experts divided ALL into 3 subtypes. The FAB system was based only on the way the leukemia cells looked under the microscope after routine staining.

French-American-British (FAB) Classification of ALL

FAB Subtype	Approximate % of Adult ALL Patients	Immunologic Type	Comments
L1	30%	T cell or pre-B cell
L2	65%	T cell or pre-B cell
L3	5%	B cell	Poor prognosis with standard therapy. Also called Burkitt leukemia.

This system has largely been replaced, as newer lab tests now allow doctors to classify ALL more accurately.

Classification based on immunophenotype

More recently, doctors have found that cytogenetic tests, flow cytometry, and other lab tests provide more detailed information about the subtype of ALL and the patient's prognosis. These tests help divide ALL into groups based on the immunophenotype of the leukemia, which takes into account the type of lymphocyte (B cell or T cell) the leukemia cells come from and on how mature these cells are. These groups have largely replaced the FAB classification. The subtypes of ALL are now named as follows:

B-cell ALL

• Early pre-B ALL (also called pro-B ALL) -- about 10% of cases
• Common ALL - about 50% of cases
• Pre-B ALL - about 10% of cases
• Mature B-cell ALL (Burkitt leukemia) -- about 4% of cases

T-cell ALL

• Pre-T ALL - about 5% to 10% of cases
• Mature T-cell ALL - about 15% to 20% of cases

The subtypes of ALL carry slightly different outlooks, but other factors (like gene changes in the leukemia cells) may also have an impact. Some of these prognostic factors are listed in the next section.

Mixed lineage acute leukemias

In recent years, newer lab tests have shown that a small number of ALL cases actually have both lymphocytic and myeloid features. Sometimes the leukemia cells have both myeloid and lymphocytic traits in the same cells. In other cases, a leukemia patient may have some cells with myeloid features and others with lymphocytic features. These types of leukemias may be called mixed lineage leukemia, ALL with myeloid markers (My+ ALL), AML with lymphoid markers, or biphenotypic acute leukemia (BAL).

Most studies suggest these leukemias tend to have a poorer outlook than standard subtypes of ALL or AML. There is no standard treatment for these leukemias. Intensive treatment (such as stem cell transplant) is often used when possible, as they have a high risk of recurrence after treatment.

Prognostic factors

As leukemia treatment has improved over the years, research has focused on why some patients have a better chance for cure than others. 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 get more or less treatment. These prognostic factors include the patient's age, white blood cell count, ALL subtype, cytogenetic test results, and response to chemotherapy.

Age: Younger patients tend to have a better prognosis than older patients. There is no set cutoff for this, but generally those younger than 50 do better than those in their 50s, while people in their 50s do better than those in their 60s or older.

• Initial white blood cell count: People with a lower WBC count (less than 30,000 for B-cell ALL and less than 100,000 for T-cell ALL) at the time of diagnosis tend to have a better prognosis.
• ALL subtype: In general, T-cell ALL has a better prognosis, while mature B-cell ALL (Burkitt leukemia) has a poorer prognosis. Other subtypes of B-cell ALL fall somewhere in between. It's important to note that this doesn't apply to all cases. For instance, some subtypes of T-cell ALL have a better outlook than others.
• Chromosome abnormalities: The presence of Philadelphia chromosome (a translocation between chromosomes 9 and 22), which is found in 25% to 30% of ALL cases, predicts a poorer prognosis. The same is true of a translocation between chromosomes 4 and 11, which is found in about 5% of cases. An extra chromosome 8 or a missing chromosome 7 also predicts a poorer outlook.
• Response to chemotherapy: Patients who achieve a complete remission (no evidence of leukemia remaining) within 4 to 5 weeks of starting treatment tend to have a better prognosis than those in whom this takes longer. Patients who don't achieve a complete remission at all have a poorer outlook. The prognostic value of minimal residual disease (described below) is still being studied.

Status of acute lymphocytic leukemia after treatment

How well a leukemia responds to treatment 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 lab tests, such as PCR.

Minimal residual disease (MRD) is a term used after treatment when leukemia cells can't be found in the bone marrow using standard lab 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. Patients with MRD after treatment are more likely to have their leukemia relapse (come back after treatment) and overall have a poorer outlook. Doctors are looking to see if these patients may benefit from further or more intensive treatment.

Active disease means that either there is evidence that the leukemia is still present during treatment or that the disease has relapsed (come back) after treatment. For a patient to be in relapse, they must have more than 5% blast cells present in the bone marrow.

How is acute lymphocytic leukemia treated?

General information

This section starts with general comments about types of treatments used for acute lymphocytic leukemia (ALL). This is followed by a discussion of the typical treatment approach for ALL in adults.

Adult acute lymphocytic leukemia (ALL) is not a single disease. It is really a group of related diseases, and patients with different subtypes of ALL vary in their outlook and response to treatment. Treatment options for each patient are based on the leukemia subtype as well as certain prognostic features (described in "How is acute lymphocytic leukemia classified?").

Several types of treatment may be used in people with ALL. The main treatment for ALL is chemotherapy. Surgery and radiation therapy may be used in special circumstances.

Chemotherapy

Chemotherapy (chemo) is the use of drugs to treat cancer. Most often, these drugs are injected into a vein, into a muscle, under the skin, or taken by mouth. entering the bloodstream to reach cancer cells all over the body. This makes chemo useful for cancers such as leukemia that has spread throughout the body. Most chemo doesn't reach the area around the brain and spinal cord well. That's why it may need to be injected into the cerebrospinal fluid (CSF) to kill cancer cells in that area.

Doctors give chemotherapy in cycles, with each period of treatment followed by a rest period to allow the body time to recover. Because of its potential side effects, chemotherapy is sometimes not recommended for patients in poor health, but advanced age by itself is not a barrier to getting chemotherapy.

Chemotherapy for ALL uses a combination of several anti-cancer drugs given over a long period of time (usually about 2 years). The most commonly used drugs include:

• Vincristine (Oncovin®)
• Daunorubicin (daunomycin or Cerubidine®) or doxorubicin (Adriamycin®)

Cytarabine (cytosine arabinoside, ara-C, or Cytosar®)

• L-asparaginase (Elspar®) or PEG-L-asparaginase (pegaspargase or Oncaspar®)
• Etoposide (VP-16)
• Teniposide (Vumon®)
• 6-mercaptopurine (6-MP or Purinethol®)
• Methotrexate (mtx)
• Cyclophosphamide (Cytoxan®)
• Prednisone (numerous brand names)
• Dexamethasone (Decadron®, others)

Possible side effects

Chemotherapy drugs work by attacking cells that are dividing quickly, which is why they work against cancer cells. But other cells in the body, such as those in the bone marrow, the lining of the mouth and intestines, and the hair follicles, also divide quickly. These cells are also likely to be affected by chemotherapy, which can lead to side effects.

The side effects of chemotherapy depend on the type and dose of drugs given and the length of time they are taken. Common side effects may include:

• Hair loss
• Mouth sores
• Loss of appetite
• Nausea and vomiting
• Low blood counts

Chemotherapy often affects the bone marrow, leading to low blood counts. This can lead to:

• Increased risk of infections (due to low white blood cell counts)
• Easy bruising or bleeding (due to low blood platelets)
• Fatigue (due to low red blood cells)

These side effects are usually short-term and go away once treatment is finished. There are often ways to lessen these side effects. For example, drugs can be given to help prevent or reduce nausea and vomiting. Be sure to ask your doctor or nurse about medicines to help reduce side effects, and let him or her know when you do have side effects so they can be managed effectively.

Drugs known as growth factors (G-CSF and GM-CSF, for example) are sometimes given to increase the white blood cell counts during chemotherapy to reduce the chance for serious infection. Because they may hasten the recovery of the white blood cell count and do not seem to cause any harm, they are often used during chemotherapy in patients with ALL.

If your white blood cell counts are very low during treatment, you can help reduce your risk of infection by carefully avoiding exposure to germs. During this time, your doctor may tell you to:

• Wash your hands often.
• Avoid fresh, uncooked fruits and vegetables and other foods that might carry germs.
• Avoid fresh flowers and plants because they may carry mold.
• Make sure other people wash their hands when they come in contact with you.
• Avoid large crowds and people who are sick (wearing a surgical mask offers protection in these situations).

Antibiotics may be given before there are signs of infection or at the earliest sign that an infection may be developing. Drugs that help prevent viral and fungal infections may also be given.

Many of the side effects of chemotherapy are caused by low white blood cell counts. Some people find it helpful to keep track of their counts. If you are interested in this, ask your doctor or nurse about your blood cell counts and what these numbers mean.

If your platelet counts are low, you may be given drugs or platelet transfusions to help protect against bleeding. Likewise, shortness of breath and extreme fatigue caused by low red blood cell counts may be treated with drugs or with red blood cell transfusions.

Some possible side effects are specific to certain drugs. For example, cytarabine (ara-C) can cause certain problems, especially when used at high doses. These can include dryness in the eyes and effects on certain parts of the brain, which can lead to coordination and balance problems.

Other organs that could be directly damaged by chemotherapy drugs include the kidneys, liver, testicles, ovaries, brain, heart, and lungs. Doctors and nurses carefully monitor treatment to reduce the risk of these side effects as much as possible.

If serious side effects occur, the chemotherapy may have to be reduced or stopped, at least for a short time. Careful monitoring and adjustment of drug doses are important because some side effects can be permanent.

One of the most serious side effects of ALL therapy is an increased risk of getting acute myelogenous leukemia (AML) at a later time. This occurs in about 5% of patients after they have received chemotherapy drugs called epipodophyllotoxins (etoposide, teniposide) or alkylating agents (cyclophosphamide, chlorambucil). Less often, people cured of leukemia may later develop non-Hodgkin lymphoma or other cancers. Of course, the risk of getting these second cancers must be balanced against the obvious benefit of treating a life-threatening disease such as leukemia with chemotherapy.

Tumor lysis syndrome is another possible side effect of chemotherapy. It can be seen in patients who had large numbers of leukemia cells in the body before treatment. When chemotherapy kills these cells, they break open and release their contents into the bloodstream. This can overwhelm the kidneys, which aren't able to get rid of all of these substances at once. Excess amounts of certain minerals may also affect the heart and nervous system. This can be prevented by giving extra fluids during treatment and by giving certain drugs, such as bicarbonate, allopurinol, and rasburicase, which help the body get rid of these substances. .

Targeted therapy

In recent years, new drugs that target specific parts of cancer cells have been developed. These drugs work differently than standard chemotherapy drugs. They often have different (and less severe) side effects. These drugs are often referred to as targeted therapy. Some of these drugs can be useful in certain cases of ALL.

For instance, drugs such as imatinib (Gleevec®), dasatinib (Sprycel®), and nilotinib (Tasigna®) specifically attack cells that have the Philadelphia chromosome (a shortened chromosome 22 that results from a translocation with chromosome 9). Both of these drugs are approved by the Food and Drug Administration to treat Philadelphia chromosome positive ALL, although dasatinib is only approved for use after imatinib stops working.

About 25% to 30% of adult patients with ALL have leukemia cells with this abnormal chromosome. Studies are now being done to find out if these drugs can be combined with chemotherapy to get better outcomes. Early reports have found that they may help more patients achieve a remission after treatment and may help keep the leukemia from coming back, but larger studies are needed to confirm this.

These drugs are taken daily as pills. Possible side effects include diarrhea, nausea, muscle pain, fatigue, and skin rashes. These are generally mild. A common side effect is swelling around the eyes or in the hands or feet. Some studies suggest this fluid buildup may rarely be due to the drugs' effects on the heart. Other possible side effects include lower red blood cell and platelet counts at the start of treatment. All of these side effects get worse at higher than usual doses of the drug.

Surgery

Surgery has a very limited role in the treatment of ALL. Because leukemia cells spread widely throughout the bone marrow and to many other organs, it is not possible to cure this type of cancer by surgery. Aside from a possible lymph node biopsy, surgery rarely has any role even in the diagnosis, since a bone marrow aspirate and biopsy can usually diagnose leukemia.

Often before chemotherapy is about to start, surgery is needed to insert a small plastic tube, called a central venous catheter or venous access device (VAD), into a large vein. The end of the tube is just under the skin or sticks out in the chest area or upper arm. The VAD is left in place during treatment to give intravenous (IV) drugs such as chemotherapy and to take blood samples. This lowers the number of needle sticks needed during treatment. It is very important to learn how to care for the device to keep it from getting infected.

Radiation therapy

Radiation therapy uses high-energy radiation to kill cancer cells. It is not usually part of the main treatment for people with ALL, but it is used in certain situations.

External beam radiation therapy, in which a machine delivers a beam of radiation to a specific part of the body, is the type of radiation used most often for ALL. Before your treatment starts, the radiation team will take careful measurements to determine the correct angles for aiming the radiation beams and the proper dose of radiation. Radiation therapy is much like getting an x-ray, but the radiation is more intense. The procedure itself is painless. Each treatment lasts only a few minutes, although the setup time -- getting you into place for treatment -- usually takes longer.

There are a few instances in which radiation therapy may be used to help treat leukemia:

• Radiation is sometimes used to treat leukemia that has spread to the brain and spinal fluid or to the testicles.
• Radiation to the whole body is often an important part of treatment before a bone marrow or peripheral blood stem cell transplant (see the section, "Bone marrow or peripheral blood stem cell transplant").
• Radiation is used (rarely) to help shrink a tumor if it is pressing on the trachea (windpipe) and causing breathing problems. But chemotherapy is often used instead, as it may work more quickly.
• Radiation can also be used to reduce pain in an area of bone that is invaded by leukemia, if chemotherapy hasn't helped.

The possible side effects of radiation therapy depend on where the radiation is aimed. Sunburn-like skin changes in the treated area are possible. Radiation to the abdomen can sometimes cause nausea, vomiting, or diarrhea. For radiation that includes large parts of the body, the effects may include fatigue and an increased risk of infection.

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Bone marrow or peripheral blood stem cell transplant

The usual doses of chemotherapy drugs can cause serious side effects to quickly dividing tissues such as the bone marrow. Unfortunately, in many cases standard doses of chemotherapy aren't able to cure ALL. Even though higher doses of these drugs might be more effective, they are not given because they could severely damage the bone marrow, which is where new blood cells are formed. This could lead to life-threatening infections, bleeding, and other problems due to low blood cell counts.

A stem cell transplant (SCT) allows doctors to use higher doses of chemotherapy and, sometimes, radiation therapy. After treatment is finished, the patient receives a transplant of blood-forming stem cells to restore the bone marrow.

Blood-forming stem cells used for a transplant are obtained either from the blood (for a peripheral blood stem cell transplant, or PBSCT) or from the bone marrow (for a bone marrow transplant, or BMT). Bone marrow transplants were more common in the past, but they have largely been replaced by PBSCT.

Types of transplants

There are 2 main types of stem cell transplants: allogeneic and autologous. They differ in the source of the blood-forming stem cells.

Allogeneic stem cell transplant

In an allogeneic transplant, the stem cells come from someone else -- usually a donor whose tissue type is almost identical to the patient's. Tissue type is based on certain substances on the surface of cells in the body. These substances can cause the immune system to react against the cells. Therefore, the closer a tissue "match" is between the donor and the recipient, the better the chance the transplanted cells will "take" and begin making new blood cells.

The donor may be a brother or sister if they are a good match. Less often, a matched unrelated donor (MUD) may be found. The stem cells from an unrelated donor come from volunteers whose tissue type has been stored in a central registry and matched with the patient’s tissue type. Sometimes umbilical cord stem cells are used. These stem cells come from blood drained from the umbilical cord and placenta after a baby is born and the umbilical cord is cut.

An allogeneic stem cell transplant may be more effective than an autologous transplant because of the "graft versus leukemia" effect. When the donor immune cells are infused into the body, they may recognize any remaining leukemia cells as being foreign to them and will attack them. This effect doesn't happen with autologous stem cell transplants.

An allogeneic transplant is the preferred type of transplant for ALL when it is available, but its use is limited because of the need for a matched donor. Its use is also limited by its side effects, which are often too severe for most people over 55 to 60 years old.

Non-myeloablative transplant: Many people over the age of 55 will not be able to tolerate a standard allogeneic transplant that uses high doses of chemotherapy. Some, however, may be able to have a non-myeloablative transplant (also known as a mini-transplant or reduced-intensity transplant), where they receive lower doses of chemotherapy and radiation that do not completely destroy the cells in their bone marrow. Then they receive the allogeneic (donor) stem cells. These cells enter the body and establish a new immune system, which sees the leukemia cells as foreign and attacks them (a "graft-versus-leukemia" effect).

Doctors have learned that if they use smaller doses of certain chemotherapy drugs and lower doses of total body radiation, an allogeneic transplant can still sometimes work with much less toxicity. In fact, a patient can receive a non-myeloablative transplant as an outpatient. The major complication is graft-versus-host disease (this is discussed in detail later in this section).

This is not a standard treatment for ALL, and studies are under way to determine how useful it may be.

Autologous stem cell transplant

In an autologous transplant, a patient's own stem cells are removed from his or her bone marrow or peripheral blood. They are frozen and stored while the person gets treatment (high-dose chemotherapy and/or radiation). A process called purging may be used to try to remove any leukemia cells in the samples. The stem cells are then reinfused into the patient's blood after treatment.

Autologous transplants are sometimes used for people with ALL who are in remission after initial treatment. Some doctors feel that it is better than standard consolidation chemotherapy (see "Typical treatment of acute lymphocytic leukemia"), but not all doctors agree with this.

One problem with autologous transplants is that it is hard to separate normal stem cells from leukemia cells in the bone marrow or blood samples. Even after purging (treating the stem cells in the lab to try to kill or remove any remaining leukemia cells), there is the risk of returning some leukemia cells with the stem cell transplant.

The transplant procedure

Blood-forming stem cells from the bone marrow or peripheral blood are collected, frozen, and stored. The patient receives high-dose chemotherapy and sometimes also radiation treatment to the entire body. (Radiation shields are used to protect the lungs, heart, and kidneys from damage during radiation therapy.)

The treatments are meant to destroy any cancer cells in the body. They also kill the normal cells of the bone marrow and the immune system. After these treatments, the frozen stem cells are thawed and given as a blood transfusion. The stem cells settle into the patient's bone marrow over the next several days and start to grow and make new blood cells.

In an allogeneic SCT, the person getting the transplant may be given drugs to keep the new immune system in check. For the next few weeks the patient gets regular blood tests and supportive therapies as needed, which might include antibiotics, red blood cell or platelet transfusions, other medicines, and help with nutrition.

Usually within a couple of weeks after the stem cells have been infused, they begin making new white blood cells. This is followed by new platelet production and, several weeks later, new red blood cell production.

Patients usually stay in the hospital in protective isolation (guarding against exposure to germs) until their white blood cell count rises above 500. They may be able to leave the hospital when their white blood cell count is near 1,000. The patient is then seen in an outpatient clinic almost every day for several weeks. Because platelet counts take longer to return to a safe level, patients may get platelet transfusions as an outpatient.

Practical points

Bone marrow or peripheral blood SCT is a complex treatment. If the doctors think a patient may benefit from a transplant, it should be done at a hospital where the staff has experience with the procedure and with managing the recovery phase. Some bone marrow transplant programs may not have experience in certain types of transplants, especially transplants from unrelated or mismatched donors.

SCT is very expensive (more than $100,000) and often requires a lengthy hospital stay. Because some insurance companies may view it as an experimental treatment, they may not pay for the procedure. It is important to find out what your insurer will cover before deciding on a transplant to get an idea of what you might have to pay.

Possible side effects

Side effects from SCT are generally divided into early and long-term effects.

The early complications and side effects are basically the same as those caused by any other type of high-dose chemotherapy (see the "Chemotherapy" section of this document), and are due to damage to the bone marrow and other quickly dividing tissues of the body. They can include low blood cell counts (with fatigue and an increased risk of infection and bleeding), nausea, vomiting, loss of appetite, mouth sores, and hair loss.

One of the most common and serious short-term effects is the increased risk for infection from bacteria, viruses, or fungi. Antibiotics are often given to try to prevent infections. Other side effects, like low red blood cell and platelet counts, may require blood product transfusions or other treatments.

A rare but serious side effect of stem cell transplant is called veno-occlusive disease of the liver (VOD). In this disease, the high doses of chemo given for transplant cause liver damage. Symptoms include weight gain (from fluid retention), liver enlargement, and jaundice (yellowing of the skin and eyes). When severe, it can lead to liver failure, kidney failure, and even death. Another name for this is sinuosoidal obstruction syndrome.

Some complications and side effects can persist for a long time or may not occur until months or years after the transplant. These include:

• Graft-versus-host disease (GVHD), which can occur in allogeneic (donor) transplants.

Damage to the lungs, causing shortness of breath

• Damage to the ovaries in women, causing infertility and loss of menstrual periods
• Damage to the thyroid gland that causes problems with metabolism
• Cataracts (damage to the lens of the eye that can affect vision)
• Bone damage called aseptic necrosis (where the bone dies because of poor blood supply). If damage is severe, the patient will need to have part of the bone and the joint replaced.

Graft-versus-host disease is the most serious complication of allogeneic (donor) stem cell transplants. This happens when the donor immune system cells attack the patient's normal cells and tissues. The areas most often affected include the skin, liver, and digestive tract, but other areas may be affected as well. GVHD is often described as either acute or chronic, based on how soon after the transplant it begins. In severe cases, GVHD can be life-threatening. Drugs that weaken the immune system are given as a part of the transplant to try to prevent GVHD.

The most common symptoms are severe skin rashes and severe diarrhea. If the liver is affected, the damage can lead to jaundice (yellowing of the skin and eyes) or even liver failure. GVHD can also cause lung damage, leading to problems breathing. The patient may feel weak, become tired easily, and have muscle aches. Sometimes GVHD becomes chronic and disabling and, if it is severe enough, can be life-threatening. Drugs that affect the immune system may be given to try to control it.

On the positive side, graft-versus-host disease can lead to "graft-versus-leukemia" activity. Any leukemia cells remaining after the chemotherapy and radiation therapy may be killed by the immune reaction of the donor cells.

For more information on stem cell transplants, see our document, Bone Marrow & Peripheral Blood Stem Cell Transplants.

Clinical trials

You may have had to make a lot of decisions since you've been told you have cancer. One of the most important decisions you will make is choosing which treatment is best for you. You may have heard about clinical trials being done for your type of cancer. Or maybe someone on your health care team has mentioned a clinical trial to you.

Clinical trials are carefully controlled research studies that are done with patients who volunteer for them. They are done to get a closer look at promising new treatments or procedures.

If you would like to take part in a clinical trial, you should start by asking your doctor if your clinic or hospital conducts clinical trials. You can also call our clinical trials matching service for a list of clinical trials that meet your medical needs. You can reach this service at 1-800-303-5691 or on our Web site at http://clinicaltrials.cancer.org. You can also get a list of current clinical trials by calling the National Cancer Institute's Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) or by visiting the NCI clinical trials Web site at www.cancer.gov/clinicaltrials.

There are requirements you must meet to take part in any clinical trial. If you do qualify for a clinical trial, it is up to you whether or not to enter (enroll in) it.

Clinical trials are one way to get state-of-the art cancer treatment. They are the only way for doctors to learn better methods to treat cancer. Still, they are not right for everyone.

You can get a lot more information on clinical trials in our document called Clinical Trials: What You Need to Know. You can read it on our Web site or call our toll-free number and have it sent to you.

Complementary and alternative therapies

When you have cancer you are likely to hear about ways to treat your cancer or relieve symptoms that your doctor hasn't mentioned. Everyone from friends and family to Internet groups and Web sites offer ideas for what might help you. These methods can include vitamins, herbs, and special diets, or other methods such as acupuncture or massage, to name a few.

What exactly are complementary and alternative therapies?

Not everyone uses these terms the same way, and they are used to refer to many different methods, so it can be confusing. We use complementary to refer to treatments that are used along with your regular medical care. Alternative treatments are used instead of a doctor's medical treatment.

Complementary methods: Most complementary treatment methods are not offered as cures for cancer. Mainly, they are used to help you feel better. Some methods that are used along with regular treatment are meditation to reduce stress, acupuncture to help relieve pain, or peppermint tea to relieve nausea. Some complementary methods are known to help, while others have not been tested. Some have been proven not be helpful, and a few have even been found harmful.

Alternative treatments: Alternative treatments may be offered as cancer cures. These treatments have not been proven safe and effective in clinical trials. Some of these methods may pose danger, or have life-threatening side effects. But the biggest danger in most cases is that you may lose the chance to be helped by standard medical treatment. Delays or interruptions in your medical treatments may give the cancer more time to grow and make it less likely that treatment will help.

Finding out more

It is easy to see why people with cancer think about alternative methods. You want to do all you can to fight the cancer, and the idea of a treatment with no side effects sounds great. Sometimes medical treatments like chemotherapy can be hard to take, or they may no longer be working. But the truth is that most of these alternative methods have not been tested and proven to work in treating cancer.

As you consider your options, here are 3 important steps you can take:

• Look for "red flags" that suggest fraud. Does the method promise to cure all or most cancers? Are you told not to have regular medical treatments? Is the treatment a "secret" that requires you to visit certain providers or travel to another country?
• Talk to your doctor or nurse about any method you are thinking about using.
• Contact us at 1-800-227-2345 to learn more about complementary and alternative methods in general and to find out about the specific methods you are looking at.

The choice is yours

Decisions about how to treat or manage your cancer are always yours to make. If you want to use a non-standard treatment, learn all you can about the method and talk to your doctor about it. With good information and the support of your health care team, you may be able to safely use the methods that can help you while avoiding those that could be harmful.

Typical treatment of acute lymphocytic leukemia

The main treatment for ALL in adults involves the long-term use of chemotherapy. In the last several years, doctors have begun to use more intensive chemotherapy regimens, which has led to more responses to treatment. But these regimens are also more likely to cause side effects, such as low white blood cell counts. Patients may need to take other drugs to help prevent or treat these side effects.

Treatment typically takes place in 3 phases:

• Induction (or remission induction)
• Consolidation (intensification)
• Maintenance

The total treatment usually takes about 2 years, with the maintenance phase taking up most of this time. Treatment may be more or less intense, depending on the subtype of ALL and other prognostic factors.

An important part of treatment of ALL is central nervous system (CNS) prophylaxis -- treatment that is meant to ensure the leukemia does not spread to (or remain in) the brain or spinal cord. This is described in more detail below.

Induction

The initial phase of chemotherapy usually lasts for a month or so. Different combinations may be used, but they typically include the following drugs:

• Vincristine
• Dexamethasone or prednisone
• Doxorubicin (Adriamycin) or daunorubicin

Based on the patient's prognostic factors, some regimens may also include cyclophosphamide, L-asparaginase, etoposide, and/or high doses of methotrexate or cytarabine (ara-C) as part of the induction phase. For ALL patients who have the Philadelphia chromosome, targeted drugs such as imatinib (Gleevec) are often included as well.

Treatment to keep the leukemia cells from spreading to the CNS is often started at this time. This is known as CNS prophylaxis. This may include one or more of the following:

• Chemotherapy injected directly into the spinal fluid (called intrathecal chemotherapy). The drug used most often is methotrexate, but sometimes cytarabine or a steroid such as prednisone may be used as well.
• High-dose IV methotrexate
• Radiation therapy to the brain and spinal cord

Induction chemotherapy can often have serious side effects, including life-threatening infections. For this reason, close monitoring and supportive care with other drugs such as antibiotics is important.

Consolidation (intensification)

If the patient goes into remission, the next phase often consists of fairly short course of chemotherapy, using many of the same drugs that were used for induction therapy. This typically lasts for a few months. Usually the drugs are given in high doses so that the treatment is still fairly intense. CNS prophylaxis may be continued at this time.

Some patients who go into remission are still at high risk for relapse, such as those who have certain subtypes of ALL or other poor prognostic factors. Doctors may suggest an allogeneic stem cell transplant (SCT) at this time, especially for those who have a brother or sister who would be a good donor match. An autologous SCT may be another option. The possible risks and benefits of stem cell transplants need to be weighed carefully, as it's still not clear how helpful they are. Patients considering this procedure may best be served by having it done in the context of a clinical trial at a center that has done a lot of SCT procedures.

Maintenance

After consolidation, the patient is generally put on a maintenance chemotherapy program of methotrexate and 6-mercaptopurine (6-MP). In some cases, this may be combined with other drugs such as vincristine and prednisone. For ALL patients who have the Philadelphia chromosome, the targeted drug imatinib is often included as well. Maintenance usually lasts for about 2 years. CNS prophylaxis may be continued at this time.

Some doctors feel that maintenance therapy may not be needed for some leukemias such as T-cell ALL and mature B-cell ALL (Burkitt leukemia).

Response rates to treatment

In general, about 80% to 90% of adults will have complete remissions after these treatments. That means leukemia cells can no longer be seen in their bone marrow. Unfortunately, about half of these patients relapse, so the overall cure rate is around 30% to 40%. Again, these rates vary depending on the subtype of ALL and other prognostic factors. For example, long-term remission rates tend to be lower in older patients and those whose ALL cells contain the Philadelphia chromosome.

What if the leukemia doesn't respond or comes back after treatment?

If the leukemia is refractory -- that is, if it doesn't go away with the first treatment (which happens in about 10% to 20% of cases) -- then newer or more intensive doses of drugs may be tried, although they are less likely to work. A stem cell transplant may be tried if the leukemia can be put into at least partial remission. Clinical trials of new treatment approaches may also be considered.

If leukemia comes back (recurs) after initial treatment, it will most often do so in the bone marrow and blood. Occasionally, the brain or spinal fluid will be the first place it recurs.

In these cases, it is sometimes possible to put the leukemia into remission again with more chemotherapy, although this remission is not likely to last. ALL patients with the Philadelphia chromosome who were taking imatinib (Gleevec) are often switched to dasatinib (Sprycel) or nilotinib (Tasigna). For patients with T cell leukemia, the drug nelarabine (Arranon®) may be helpful.

If a second remission can be achieved, most doctors will advise some type of stem cell transplant if possible.

If the leukemia doesn't go away or keeps coming back, eventually chemotherapy treatment will not be very helpful. If a stem cell transplant is not an option, a patient may want to consider taking part in a clinical trial of newer treatments.

Those who want to continue treatment to fight the leukemia as long as they can need to weigh the possible limited benefit of a new treatment against the possible downsides, including continued doctor visits and treatment side effects. Everyone has his or her own way of looking at this. In many cases, the doctor can estimate the response rate for the treatment being considered. Some people are tempted to try more chemotherapy, for example, even when their doctors say that the odds of benefit are less than 1%. In this situation, it is important to think about and understand your reasons for choosing this plan.

Palliative treatment

If a clinical trial is not an option, it is important at this time to focus on relieving the symptoms of the leukemia. This is known as palliative treatment. For example, the doctor may advise less intensive chemotherapy to try to slow the leukemia growth instead of trying to cure it.

As the leukemia grows in the bone marrow it may cause pain. It is important that you be as comfortable as possible. Treatments that may be helpful include radiation and appropriate pain-relieving medicines. If medicines such as aspirin and ibuprofen don't help with the pain, stronger opioid medicines such as morphine are likely to be helpful.

Other common symptoms from leukemia are low blood counts and fatigue. Medicines or blood transfusions may be needed to help correct these problems. Nausea and loss of appetite can be treated with medicines and high-calorie food supplements. Infections that occur may be treated with antibiotics.

More treatment information

For more details on treatment options -- including some that may not be addressed in this document -- the National Cancer Institute (NCI) is a good source of information.

The NCI provides treatment guidelines via its telephone information center (1-800-4-CANCER) and its Web site (www.cancer.gov). Detailed guidelines intended for use by cancer care professionals are also available on www.cancer.gov.

What should you ask your doctor about acute lymphocytic leukemia?

It is important to have frank, honest, open discussions with your doctor. You should feel free to ask any question that's on your mind, no matter how small it might seem. Here are some questions you might want to ask. Nurses, social workers, and other members of the treatment team may also be able to answer many of your questions.

• What kind of acute lymphocytic leukemia (ALL) do I have?
• Are there any specific factors that might affect my prognosis?
• Are there other tests that need to be done before we can decide on treatment?
• How much experience do you have treating this type of leukemia?
• Should I get a second opinion?
• What treatment choices do I have?
• Should we consider a stem cell transplant? When?
• Which treatment do you recommend, and why?
• What are the risks and side effects to the treatments that you recommend?
• What should I do to be ready for treatment?
• How long will treatment last? What will it involve? Where will it be done?
• How will treatment affect my daily activities?
• What is the outlook for my survival?
• What would we do if the treatment doesn't work or if the leukemia recurs?
• What type of follow-up will I need after treatment?

Be sure to write down any questions you have that are not on this list. For instance, you might want specific information about recovery times so that you can plan your work schedule. Or you may want to ask about clinical trials for which you may qualify. Taking another person and/or a tape recorder to the appointment can be helpful.

What happens after treatment for acute lymphocytic leukemia?

Completing treatment can be both stressful and exciting. You will be relieved to finish treatment, yet it is hard not to worry about the leukemia coming back. This is a very common concern among those who have had cancer.

It may take a while before your fears lessen. But it may help to know that many cancer survivors have learned to live with this uncertainty and are living full lives. Our document, Living With Uncertainty: The Fear of Cancer Recurrence, gives more detailed information on this.

Follow-up care

Treatment for acute lymphocytic leukemia lasts for years. Even after treatment ends, your doctors will still want to watch you closely. It is very important to go to all of your follow-up appointments. During these visits, your doctors will ask questions about any problems you may have and may do exams and lab tests or x-rays and scans to look for signs of leukemia or treatment side effects. Almost any cancer treatment can have side effects. Some may last for a few weeks to months, but others can last the rest of your life. This is the time for you to talk to your cancer care team about any changes or problems you notice and any questions or concerns you have.

If a relapse occurs, it is usually while the patient is being treated or shortly after they have finished chemotherapy. If this happens, treatment would be as described in the section, "What if the leukemia doesn't respond or comes back after treatment?" It is unusual for ALL to return if there are still no signs of the disease within 5 years after treatment.

It is important to keep health insurance. Tests and doctor visits cost a lot, and even though no one wants to think of their cancer coming back, this could happen.

Should your cancer come back, our document, When Your Cancer Comes Back: Cancer Recurrence can give you information on how to manage and cope with this phase of your treatment.

Seeing a new doctor

At some point after your cancer diagnosis and treatment, you may find yourself seeing a new doctor who does not know anything about your medical history. It is important that you be able to give your new doctor the details of your diagnosis and treatment. Make sure you have this information handy:

A copy of your pathology report(s) from any biopsies or surgeries

• If you had surgery, a copy of your operative report(s)
• If you were hospitalized, a copy of the discharge summary that doctors must prepare when patients are sent home
• If you had radiation therapy, a copy of your treatment summary

If you had chemotherapy or other medicines like targeted therapy), a list of your drugs, drug doses, and when you took them

The doctor may want copies of this information for his records, but always keep copies for yourself.

Lifestyle changes

You can't change the fact that you have had cancer. What you can change is how you live the rest of your life -- making choices to help you stay healthy and feel as well as you can. This can be a time to look at your life in new ways. Maybe you are thinking about how to improve your health over the long term. Some people even start during cancer treatment.

Making healthier choices

For many people, a diagnosis of cancer helps them focus on their health in ways they may not have thought much about in the past. Are there things you could do that might make you healthier? Maybe you could try to eat better or get more exercise. Maybe you could cut down on the alcohol, or give up tobacco. Even things like keeping your stress level under control may help. Now is a good time to think about making changes that can have positive effects for the rest of your life. You will feel better and you will also be healthier.

You can start by working on those things that worry you most. Get help with those that are harder for you. For instance, if you are thinking about quitting smoking and need help, call the American Cancer Society at 1-800-227-2345 for information and support.

Eating better

Eating right can be hard for anyone, but it can get even tougher during and after cancer treatment. Treatment may change your sense of taste. Nausea can be a problem. You may not feel like eating and lose weight when you don't want to. Or you may have gained weight that you can't seem to lose. All of these things can be very frustrating.

If treatment caused weight changes or eating or taste problems, do the best you can and keep in mind that these problems usually get better over time. You may find it helps to eat small portions every 2 to 3 hours until you feel better. You may also want to ask your cancer team about seeing a dietitian, an expert in nutrition who can give you ideas on how to deal with these treatment side effects.

One of the best things you can do after cancer treatment is put healthy eating habits into place. You may be surprised at the long-term benefits of some simple changes, like increasing the variety of healthy foods you eat. Try to eat 5 or more servings of vegetables and fruits each day. Choose whole grain foods instead of those made with white flour and sugars. Try to limit meats that are high in fat. Cut back on processed meats like hot dogs, bologna, and bacon. Better yet, don't eat any of these, if you can. If you drink alcohol, limit yourself to 1 or 2 drinks a day at the most.

Rest, fatigue, work, and exercise

Extreme tiredness, called fatigue, is very common in people treated for cancer. This is not a normal tiredness, but a "bone-weary" exhaustion that doesn't get better with rest. For some people, fatigue lasts a long time after treatment, and can make it hard for them to exercise and do other things they want to do. But exercise can help reduce fatigue. Studies have shown that patients who follow an exercise program tailored to their personal needs feel better physically and emotionally and can cope better, too.

If you were sick and not very active during treatment, it is normal for your fitness, endurance, and muscle strength to decline. Any plan for physical activity should fit your own situation. An older person who has never exercised will not be able to take on the same amount of exercise as a 20-year-old who plays tennis twice a week. If you haven't exercised in a few years, you will have to start slowly -- maybe just by taking short walks.

Talk with your health care team before starting anything. Get their opinion about your exercise plans. Then, try to find an exercise buddy so you're not doing it alone. Having family or friends involved when starting a new exercise program can give you that extra boost of support to keep you going when the push just isn't there.

If you are very tired, you will need to balance activity with rest. It is OK to rest when you need to. Sometimes it's really hard for people to allow themselves to rest when they are used to working all day or taking care of a household, but this is not the time to push yourself too hard. Listen to your body and rest when you need to. (For more information on dealing with fatigue, please see Fatigue in People With Cancer and Anemia in People With Cancer.)

Keep in mind exercise can improve your physical and emotional health.

• It improves your cardiovascular (heart and circulation) fitness.
• Along with a good diet, it will help you get to and stay at a healthy weight.
• It makes your muscles stronger.
• It reduces fatigue and helps you have more energy.
• It can help lower anxiety and depression.
• It makes you feel happier.
• It helps you feel better about yourself.

And long term, we know that exercise plays a role in helping to lower the risk of some cancers. In the American Cancer Society guidelines on physical activity for cancer prevention, we recommend that adults take part in at least 30 minutes of moderate to vigorous physical activity, above usual activities, on 5 or more days of the week; 45 to 60 minutes of intentional physical activity are even better

.

How about your emotional health?

When treatment ends, you may find yourself overcome with many different emotions. This happens to a lot of people. You may have been going through so much during treatment that you could only focus on getting through each day. Now it may feel like a lot of other issues are catching up with you.

You may find yourself thinking about death and dying. Or maybe you're more aware of the effect the cancer has on your family, friends, and career. You may take a new look at your relationship with those around you. Unexpected issues may also cause concern. For instance, as you feel better and have fewer doctor visits, you will see your health care team less often and have more time on your hands. These changes can make some people anxious.

Almost everyone who has been through cancer can benefit from getting some type of support. You need people you can turn to for strength and comfort. Support can come in many forms: family, friends, cancer support groups, church or spiritual groups, online support communities, or one-on-one counselors. What's best for you depends on your situation and personality. Some people feel safe in peer-support groups or education groups. Others would rather talk in an informal setting, such as church. Others may feel more at ease talking one-on-one with a trusted friend or counselor. Whatever your source of strength or comfort, make sure you have a place to go with your concerns.

The cancer journey can feel very lonely. It is not necessary or good for you to try to deal with everything on your own. And your friends and family may feel shut out if you do not include them. Let them in, and let in anyone else who you feel may help. If you aren’t sure who can help, call your American Cancer Society at 1-800-227-2345 and we can put you in touch with a group or resource that may work for you.

If treatment stops working

If the leukemia keeps growing or comes back after one kind of treatment, it is possible that another treatment plan might still cure the cancer, or at least treat it enough to help you live longer and feel better. But when a person has tried many different treatments and the leukemia doesn't go away, the leukemia tends to become resistant to all treatment. If this happens, it's important to weigh the possible limited benefits of a new treatment against the possible downsides. Everyone has their own way of looking at this.

This is likely to be the hardest part of your battle with cancer -- when you have been through many medical treatments and nothing's working anymore. Your doctor may offer you new options, but at some point you may need to consider that treatment is not likely to improve your health or change your outcome or survival.

If you want to continue to get treatment for as long as you can, you need to think about the odds of treatment having any benefit and how this compares to the possible risks and side effects. In many cases, your doctor can estimate how likely it is the leukemia will respond to treatment you are considering. For instance, the doctor may say that more chemo or radiation might have about a 1% chance of working. Some people are still tempted to try this. But it is important to think about and understand your reasons for choosing this plan.

No matter what you decide to do, you need to feel as good as you can. Make sure you are asking for and getting treatment for any symptoms you might have, such as nausea or pain. This type of treatment is called palliative care.

Palliative care helps relieve symptoms, but is not expected to cure the disease. It can be given along with cancer treatment, or can even be cancer treatment. The difference is its purpose - the main purpose of palliative care is to improve the quality of your life, or help you feel as good as you can for as long as you can. Sometimes this means using drugs to help with symptoms like pain or nausea. Often, in leukemia, palliative care includes transfusions of red blood cells to help you feel stronger. Sometimes, though, the treatments used to control symptoms are the same as those used to treat cancer. For instance, radiation might be used to help relieve bone pain caused by cancer that has spread to the bones. Or chemo might be used to help shrink a tumor and keep it from blocking the bowels. But this is not the same as treatment to try to cure the cancer.

At some point, you may benefit from hospice care. This is special care that treats the person rather than the disease; it focuses on quality rather than length of life. Most of the time, it is given at home. Your cancer may be causing problems that need to be managed, and hospice focuses on your comfort. You should know that while getting hospice care often means the end of treatments such as chemo and radiation, it doesn't mean you can't have treatment for the problems caused by your cancer or other health conditions. In hospice the focus of your care is on living life as fully as possible and feeling as well as you can at this difficult time. You can learn more about hospice in our document called Hospice Care.

Staying hopeful is important, too. Your hope for a cure may not be as bright, but there is still hope for good times with family and friends -- times that are filled with happiness and meaning. Pausing at this time in your cancer treatment gives you a chance to refocus on the most important things in your life. Now is the time to do some things you've always wanted to do and to stop doing the things you no longer want to do. Though the cancer may be beyond your control, there are still choices you can make.

What's new in acute lymphocytic leukemia research and treatment?

Researchers are now studying the causes, diagnosis, supportive care, and treatment of leukemia at many medical centers, university hospitals, and other institutions.

Genetics of leukemia

Scientists are making great progress in understanding how changes in a person's DNA can cause normal bone marrow cells to develop into leukemia cells. A greater understanding of the genes (regions of the DNA) involved in certain translocations that often occur in acute lymphocytic leukemia (ALL) is providing insight into why these cells become abnormal. Doctors are now looking to learn how to use these changes to help them determine a person's outlook and whether they should receive more or less intensive treatment.

As this information unfolds, it may also be used in developing newer targeted therapies against ALL. Drugs such as imatinib (Gleevec) and dasatinib (Sprycel) are examples of such treatments. They are now used in treating ALL patients who have the Philadelphia chromosome.

Gene expression profiling

This new lab technique is being studied to help identify and classify different cancers. Instead of looking at single genes, this test uses a special technology to look at the patterns of many different genes in the cancer cells at the same time. This may add to the information that comes from the current lab tests. This information may eventually permit more personalized treatment by predicting which chemo drugs are likely to be most effective for each patient. These studies are also being used to find previously-unknown changes inside ALL cells to help guide researchers in developing new drugs.

Detecting minimal residual disease

Progress in understanding DNA changes in ALL has already provided a highly sensitive test for detecting minimal residual disease after treatment -- when so few leukemia cells are present that they cannot be found by routine bone marrow tests.

The polymerase chain reaction (PCR) test can identify ALL cells based on their gene translocations or rearrangements. This test can find one leukemia cell among a million normal cells. A PCR test can be useful in determining how completely the chemotherapy has destroyed the ALL cells.

Doctors are now trying to determine if patients with minimal residual disease will benefit from further or more intensive treatment.

Improving chemotherapy

Studies are in progress to find the most effective combination of chemotherapy drugs while limiting unwanted side effects. This is especially important in older patients, who often have a harder time tolerating current treatments.

New chemotherapy drugs are also being developed and tested. For example, clofarabine (Clolar®) is approved to treat childhood ALL and is now being studied to see if it helps adults with this disease. Many other new drugs are also being studied.

Studies are also under way to determine whether patients with certain unfavorable prognostic features benefit from more intensive chemotherapy, and whether some ALL patients with favorable prognostic factors might not need as much treatment.

The effectiveness of chemotherapy may be limited in some cases because the leukemia cells become resistant to it. Researchers are now looking at ways to prevent or reverse this resistance by using other drugs along with chemotherapy.

Stem cell transplants

Researchers continue to refine stem cell transplants to try to increase their effectiveness, reduce complications and determine which patients are likely to be helped by this treatment. Many studies are under way to try to help determine exactly when allogeneic, autologous, and mini-transplants might best be used.

In people who have already received an allogeneic transplant and who relapse, doctors are studying donor leukocyte infusion. In this technique, the patient gets an infusion of white blood cells (leukocytes) from the same donor who contributed to stem cells for the original transplant. The hope is that the cells will boost the new immune system and add to the graft-versus-leukemia effect. Early study results have been promising, but more research of this approach is needed.

Monoclonal antibodies

These are man-made versions of immune system proteins (antibodies). They can be targeted to attach only to certain molecules, such as proteins on the surface of lymphocytes. Some monoclonal antibodies, such as rituximab (Rituxan) and alemtuzumab (Campath), are already used to treat some blood disorders and are now being studied for use against ALL. Early results have been favorable, but it is still too early to know for sure. Studies of several other monoclonal antibodies to treat ALL are now under way as well.

Additional resources

More information from your American Cancer Society

We have some related information that may also be helpful to you. These materials may be ordered from our toll-free number, 1-800-227-2345.

After Diagnosis: A Guide for Patients and Families (Available in Spanish also)

Bone Marrow & Peripheral Blood Stem Cell Transplants

Caring for the Patient With Cancer at Home (Available in Spanish also)

Nutrition for the Person With Cancer: A Guide for Patients and Families (also available in Spanish)

Understanding Chemotherapy -- A Guide for Patients and Families (Available in Spanish also)

When Your Cancer Comes Back: Cancer Recurrence

The following books are available from the American Cancer Society. Call us at 1-800-227-2345 to ask about costs or to place your order.

American Cancer Society's Guide to Pain Control

Cancer in the Family: Helping Children Cope With a Parent’s Illness

Caregiving: A Step-By-Step Resource for Caring for the Person With Cancer at Home

Coming to Terms With Cancer: A Glossary of Cancer-Related Terms

Consumers Guide to Cancer Drugs

Informed Decisions, Second Edition: The Complete Book of Cancer Diagnosis, Treatment, and Recovery

National organizations and Web sites*

In addition to the American Cancer Society, other sources of patient information and support include:

Acute lymphocytic leukemia

Leukemia & Lymphoma Society
Toll-free number: 1-800-955-4572
Web site: www.lls.org

National Cancer Institute
Toll-free number: 1-800-4-CANCER (1-800-422-6237)
Web site: www.cancer.gov

Bone marrow and peripheral blood stem cell transplants

Caitlin Raymond International Registry (for unrelated bone marrow transplants)
Toll-free number: 1-800-726-2824
Web site: www.crir.org

National Bone Marrow Transplant Link (nbmtLINK)
Toll-free number: 1-800-LINK-BMT (1-800-546-5268)
Web site: www.nbmtlink.org

National Marrow Donor Program
Toll-free number: 1-800-MARROW-2 (1-800-627-7692)
Web site: www.marrow.org

No matter who you are, we can help. Contact us anytime, day or night, for information and support. Call us at 1-800-227-2345 or visit cancer.org.

References

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American Cancer Society. Cancer Facts and Figures 2010. Atlanta, Ga: American Cancer Society; 2010.

Faderl S, O'Brien S, Pui CH, Stock W, Wetzler M, Hoelzer D, Kantarjian HM. Adult acute lymphoblastic leukemia: concepts and strategies. Cancer. 2010 Mar 1;116(5):1165-76.

Fielding A. The treatment of adults with acute lymphoblastic anemia. In: Hematology 2008. American Society of Hematology Education Program Book. 2008:381-389. Accessed at http://asheducationbook.hematologylibrary.org/cgi/content/full/2008/1/457 on April 15, 2009.

Hoelzer D, Gokbuget N. Acute lymphocytic leukemia in adults. In: Hoffman R, Benz EJ, Shattil SJ, Furie B, Cohen HJ, Silberstein LE, McGlave P, eds. Hematology: Basic Principles and Practice. 4th ed. Philadelphia, Pa: Elsevier; 2005:1175-1194.

Hoelzer D, Gokbuget N. Acute lymphocytic leukemia in adults. In: Abeloff MD, Armitage JO, Niederhuber JE. Kastan MB, McKenna WG, eds. Abeloff's Clinical Oncology. 4th ed. Philadelphia, Pa: Elsevier; 2008:2191-2213.

Kebriaei P, de Lima M, Estey E. Management of acute leukemias. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. DeVita, Hellman, and Rosenberg's Cancer: Principles and Practice of Oncology. 8th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2008:2232-2265.

National Cancer Institute. Physician Data Query (PDQ). Adult Acute Lymphoblastic Leukemia Treatment. 7/8/2010. Accessed at www.cancer.gov/cancertopics/pdq/treatment/adultALL/healthprofessional on August 23, 2010.

O'Donnell MR. Acute leukemias. In: Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ, eds. Cancer Management: A Multidisciplinary Approach. 11th ed. Lawrence, KS: CMPMedica; 2008:797-826.

Pui CH, Robison LL, Look AT. Acute lymphoblastic leukemia. Lancet. 2008;371:1030-1043.

Rowe JM, Buck G, Burnett AK, et al. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood. 2005:106;3760-3767.