Childhood Acute Lymphoblastic Leukemia Treatment (PDQ�)

General Information About Childhood Acute Lymphoblastic Leukemia

Childhood acute lymphoblastic leukemia (ALL) is a type of cancer in which the bone marrow makes too many immature lymphocytes (a type of white blood cell).

Childhood acute lymphoblastic leukemia (also called acute lymphocytic leukemia or ALL) is a cancer of the blood and bone marrow. This type of cancer usually gets worse quickly if it is not treated. It is the most common type of cancer in children.

Normally, the bone marrow makes blood stem cells (immature cells) that develop into mature blood cells over time. A blood stem cell may become a myeloid stem cell or a lymphoid stem cell.

The myeloid stem cell develops into one of three types of mature blood cells:

• Red blood cells that carry oxygen and other materials to all tissues of the body.

• Platelets that help prevent bleeding by causing blood clots to form.

• Granulocytes (white blood cells) that fight infection and disease.

The lymphoid stem cell develops into a lymphoblast cell and then into one of three types of lymphocytes (white blood cells):

• B lymphocytes that make antibodies to help fight infection.

• T lymphocytes that help B lymphocytes make the antibodies that help fight infection.

• Natural killer cells that attack cancer cells and viruses.

In ALL, too many stem cells develop into lymphoblasts and do not mature to become lymphocytes. These lymphoblasts are called leukemia cells. The leukemia cells do not work like normal lymphocytes and are not able to fight infection very well. Also, as the number of leukemia cells increases in the blood and bone marrow, there is less room for healthy white blood cells, red blood cells, and platelets. This may lead to infection, anemia, and easy bleeding.

This summary is about acute lymphoblastic leukemia. See the following PDQ summaries for information on other types of leukemia:

• Adult Acute Lymphoblastic Leukemia Treatment.

• Chronic Lymphocytic Leukemia Treatment.

• Adult Acute Myeloid Leukemia Treatment.

• Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies Treatment.

• Chronic Myelogenous Leukemia Treatment.

• Hairy Cell Leukemia Treatment.

There are subgroups of childhood ALL.

There are different subgroups of ALL based on the following:

• Whether the type of blood cell that is affected looks more like a B lymphocyte or a T lymphocyte.

• The age of the child at diagnosis. For example, whether the child is younger than one year, one year to 10 years old, or older than 10 years (teenager).

• Whether there are certain changes in the chromosomes. Philadelphia chromosome-positive ALL is one type of chromosome change that may occur.

See the Childhood Acute Lymphoblastic Leukemia Subgroups section for more information.

Family history and exposure to radiation may affect the risk of developing childhood ALL.

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn?t mean that you will not get cancer. People who think they may be at risk should discuss this with their doctor. Possible risk factors for ALL include the following:

• Having a brother or sister with leukemia.

• Being white or Hispanic.

• Living in the United States.

• Being exposed to x-rays before birth.

• Being exposed to radiation.

• Past treatment with chemotherapy or other drugs that weaken the immune system.

• Having certain changes in genes or geneticdisorders, such as Down syndrome.

Possible signs of childhood ALL include fever and bruising.

These and other symptoms may be caused by childhood ALL. Other conditions may cause the same symptoms. A doctor should be consulted if any of the following problems occur:

• Fever.

• Easy bruising or bleeding.

• Petechiae (flat, pinpoint, dark-red spots under the skin caused by bleeding).

• Bone or joint pain.

• Painless lumps in the neck, underarm, stomach, or groin.

• Pain or feeling of fullness below the ribs.

• Weakness, feeling tired, or looking pale.

• Loss of appetite.

Tests that examine the blood and bone marrow are used to detect (find) and diagnose childhood ALL.

The following tests and procedures may be used:

• Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient's health habits and past illnesses and treatments will also be taken.

• Complete blood count (CBC) with differential: A procedure in which a sample of blood is drawn and checked for the following:

  • The number of red blood cells and platelets.

  • The number and type of white blood cells.

  • The amount of hemoglobin (the protein that carries oxygen) in the red blood cells.

  • The portion of the sample made up of red blood cells.

  

• Bone marrow aspiration and biopsy: The removal of bone marrow, blood, and a small piece of bone by inserting a hollow needle into the hipbone or breastbone. A pathologist views the bone marrow, blood, and bone under a microscope to look for signs of cancer.

• Cytogenetic analysis: A laboratory test in which the cells in a sample of blood or bone marrow are viewed under a microscope to look for certain changes in the chromosomes in the lymphocytes. For example, in Philadelphia chromosome-positive ALL, part of one chromosome is moved to another chromosome. This is called the ?Philadelphia chromosome.? Other tests, such as fluorescence in situ hybridization (FISH), may also be done to look for certain changes in the chromosomes.

• Immunophenotyping: A test in which the cells in a sample of blood or bone marrow are looked at under a microscope to find out if malignant lymphocytes (cancer) began from the B lymphocytes or the T lymphocytes.

• Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it.

• Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.

Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) and treatment options may depend on:

• Age at diagnosis and race.

• How quickly and how low the leukemia cell count drops after initial treatment.

• Whether the leukemia cells began from B lymphocytes or T lymphocytes.

• Whether there are certain changes in the chromosomes of lymphocytes.

• Whether the leukemia has spread to the brain and spinal cord.

• Whether the child has Down syndrome.

If leukemia recurs (comes back) after initial treatment, the prognosis and treatment options may depend on:

• How long it is between the end of initial treatment and when the leukemia recurs.

• Whether the leukemia recurs in the bone marrow or outside the bone marrow.

Stages of Childhood Acute Lymphoblastic Leukemia

Once childhood ALL has been diagnosed, tests are done to find out if the cancer has spread to the central nervous system (brain and spinal cord), testicles, or to other parts of the body.

The extent or spread of cancer is usually described as stages. For childhood acute lymphoblastic leukemia (ALL), risk groups are used instead of stages. The following tests and procedures may be used to determine the risk group:

• Lumbar puncture: A procedure used to collect cerebrospinal fluid from the spinal column. This is done by placing a needle into the spinal column. This procedure is also called an LP or spinal tap.

• Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body. The chest x-ray is done to see if leukemiacells are forming a mass in the middle of the chest.

• Testicularbiopsy: The removal of cells or tissues from the testicles so they can be viewed under a microscope by a pathologist to check for signs of cancer. This procedure is done only if there seems to be anything unusual about the testicles during the physical exam.

There are three ways that cancer spreads in the body.

When cancer cells spread outside the blood, a solid tumor may form. This process is called metastasis. The three ways that cancer cells spread in the body are:

• Through the blood. Cancer cells travel through the blood, invade solid tissues in the body, such as the brain or heart, and form a solid tumor.

• Through the lymph system. Cancer cells invade the lymph system, travel through the lymph vessels, and form a solid tumor in other parts of the body.

• Through solid tissue. Cancer cells that have formed a solid tumor spread to tissues in the surrounding area.

The new (metastatic) tumor is the same type of cancer as the primary cancer. For example, if leukemia cells spread to the brain, the cancer cells in the brain are actually leukemia cells. The disease is metastatic leukemia, not brain cancer.

In childhood ALL, risk groups are used instead of stages.

Because ALL is a disease of the blood cells, it has already spread throughout the body at diagnosis. There is no staging system for ALL. Risk groups are used to plan treatment.

Risk groups are described as:

• Standard (low) risk: Includes children aged 1 to 9 years who have a white blood cell count of less than 50,000/�L at diagnosis.

• High risk: Includes children younger than 1 year or older than 9 years and children who have a white blood cell count of 50,000/�L or more at diagnosis.

Other factors that affect the risk group include the following:

• Whether the leukemia cells formed from B lymphocytes or T lymphocytes.

• Whether there are certain changes in the chromosomes of the lymphocytes.

• How quickly the leukemia responds to initial therapy.

It is important to know the risk group in order to plan treatment. Children with high risk ALL usually receive more aggressive treatment than children with standard risk ALL.

Recurrent Childhood Acute Lymphoblastic Leukemia

Recurrent childhood ALL is cancer that has recurred (come back) after it has been treated. The leukemia may come back in the blood and bone marrow, brain, testicles, spinal cord, or in other parts of the body.

Treatment Option Overview

There are different types of treatment for childhood acute lymphoblastic leukemia (ALL).

Different types of treatment are available for children with acute lymphoblastic leukemia (ALL). Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment.

Because cancer in children is rare, taking part in a clinical trial should be considered. Some clinical trials are open only to patients who have not started treatment.

Children with ALL should have their treatment planned by a team of doctors with expertise in treating childhood leukemia.

Treatment will be overseen by a pediatriconcologist, a doctor who specializes in treating children with cancer. The pediatric oncologist works with other pediatric health professionals who are experts in treating children with leukemia and who specialize in certain areas of medicine. These may include the following specialists:

• Hematologist.

• Medical oncologist.

• Pediatric surgeon.

• Radiation oncologist.

• Endocrinologist.

• Neurologist.

• Pathologist.

• Radiologist.

• Pediatric nurse specialist.

• Social worker.

• Rehabilitation specialist.

• Psychologist.

Regular follow-up exams are very important. Side effects can result from treatment long after it ends. These are called late effects. Radiation therapy to the head may affect the child's developing brain and cause changes in mood, feelings, thinking, learning, or memory. Late effects of treatment for ALL also include the risk of second cancers (new types of cancer), especially brain tumors. Early diagnosis and treatment of these secondary brain tumors may help lower the risk from these brain tumors. Children younger than 4 years have a higher risk of side effects from radiation therapy to the brain. It is important to talk with your child's doctors about the possible late effects caused by some treatments. See the PDQ summary on Late Effects of Treatment for Childhood Cancer.

The treatment of childhood ALL usually has 3 phases.

The treatment of childhood ALL is done in phases:

• Induction therapy: This is the first phase of treatment. Its purpose is to kill the leukemia cells in the blood and bone marrow. This puts the leukemia into remission. This is also called the remission induction phase.

• Consolidation/intensification therapy: This is the second phase of therapy. It begins once the leukemia is in remission. The purpose of consolidation/intensification therapy is to kill any remaining leukemia cells that may not be active but could begin to regrow and cause a relapse.

• Maintenance therapy: This is the third phase of treatment. Its purpose is to kill any remaining leukemia cells that may regrow and cause a relapse. Often the cancer treatments are given in lower doses than those used for induction and consolidation/intensification therapy. This is also called the continuation therapy phase.

Bone marrow biopsy and aspirates are done throughout all phases to see how well the leukemia is responding to treatment.

Treatment called central nervous system (CNS) sanctuary therapy is usually given during induction therapy and consolidation/intensification therapy and is often given during maintenance therapy. Because most anticancer drugs given by mouth or injected into a vein to kill leukemia cells may not reach leukemia cells in the CNS (brain and spinal cord), the leukemia cells are able to find ?sanctuary? (hide) in the CNS. Certain anticancer drugs, intrathecal chemotherapy, and radiation therapy to the brain are able to reach leukemia cells in the CNS and are given to kill the leukemia cells and prevent the cancer from recurring (coming back). CNS sanctuary therapy is also called CNS prophylaxis because it is given to stop leukemia cells from growing in the CNS.

Four types of standard treatment are used:

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid (intrathecal), an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). Combination chemotherapy is treatment using more than one anticancer drug. The way the chemotherapy is given depends on the type of the cancer being treated.

Intrathecal chemotherapy or high doses of chemotherapy injected into a vein may be used to treat childhood ALL that has spread, or may spread, to the brain and spinal cord. When used to prevent cancer from spreading to the brain and spinal cord, it is called central nervous system (CNS) sanctuary therapy or CNS prophylaxis. CNS sanctuary therapy is given in addition to chemotherapy by mouth or vein that is intended to kill leukemia cells in the rest of the body. All children with ALL receive CNS sanctuary therapy as part of their treatment.

See Drugs Approved for Acute Lymphoblastic Leukemia for more information.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. External radiation therapy may be used to treat childhood ALL that has spread, or may spread, to the brain and spinal cord. When used this way, it is called central nervous system (CNS) sanctuary therapy or CNS prophylaxis.

Because radiation therapy to the brain can affect growth and brain development in young children, many children with ALL are treated without radiation therapy. Radiation therapy to the brain and spinal cord is sometimes used as CNS sanctuary therapy to treat children and teenagers in the high risk group. Clinical trials are studying new ways of using radiation therapy that may have fewer side effects, including giving lower doses of radiation.

Chemotherapy with stem cell transplant

Stem cell transplant is a method of giving very high doses of chemotherapy and sometimes radiation therapy, and then replacing the blood-forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of a donor. After the patient receives very high doses of chemotherapy and sometimes radiation therapy, the donor's stem cells are given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the patient's blood cells. A stem cell transplant may use stem cells from a donor who is or is not related to the patient.

Stem cell transplant is rarely used as initial treatment for children and teenagers with ALL. It is used more often as part of treatment for ALL that relapses (comes back after treatment).

See Drugs Approved for Acute Lymphoblastic Leukemia for more information.

Targeted therapy

Targeted therapy is a treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells.

Tyrosine kinase inhibitors (TKIs) are targeted therapy drugs that block the enzyme, tyrosine kinase, which causes stem cells to develop into more white blood cells (granulocytes or blasts) than the body needs. For example, imatinib mesylate (Gleevec) is a TKI used in the treatment of children with Philadelphia chromosome-positive ALL.

See Drugs Approved for Acute Lymphoblastic Leukemia for more information.

New types of treatment are being tested in clinical trials.

This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI Web site.

High-dose chemotherapy

High-dose chemotherapy is giving high doses of anticancer drugs to kill cancer cells. This treatment often causes the bone marrow to stop making blood cells and can cause other serious side effects. High-dose chemotherapy is usually followed by stem cell transplant to restore the bone marrow. Clinical trials are studying high-dose chemotherapy for certain patients, including children whose ALL does not go into remission after induction therapy and children whose leukemia comes back after treatment (relapses).

Targeted therapy

Targeted therapy is a treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells.

New kinds of targeted therapies are being studied in the treatment of childhood ALL.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Treatment Options for Childhood Acute Lymphoblastic Leukemia

A link to a list of current clinical trials is included for each treatment section. For some types or stages of cancer, there may not be any trials listed. Check with your doctor for clinical trials that are not listed here but may be right for you.

Newly Diagnosed Childhood Acute Lymphoblastic Leukemia

Standard treatment of childhood acute lymphoblastic leukemia (ALL) during the induction, consolidation/intensification, and maintenance phases may include the following:

• Combination chemotherapy.

• CNS sanctuary therapy with intrathecal chemotherapy and high-dose chemotherapy. Sometimes radiation therapy to the brain may be given.

• Combination chemotherapy followed by stem cell transplant using stem cells from a donor.

• A clinical trial of a new combination chemotherapy and intrathecal chemotherapy regimen given with or without radiation therapy. The chemotherapy dose and/or schedule may vary depending on the patient's risk group after induction therapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with untreated childhood acute lymphoblastic leukemia. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.

Childhood Acute Lymphoblastic Leukemia Subgroups

Standard treatment of T-cell childhood acute lymphoblastic leukemia (ALL) may include the following:

• Combination chemotherapy. CNS sanctuary therapy with intrathecal chemotherapy and radiation therapy to the brain may also be given.

• A clinical trial studying a new anticancer drug, the doses of certain anticancer drugs, and the use of radiation therapy to the brain.

Standard treatment of infants with ALL may include the following:

• Combination chemotherapy. CNS sanctuary therapy with intrathecal chemotherapy may also be given

• Chemotherapy followed by a donorstem cell transplant has been studied but it is not known if this treatment improves survival.

• A clinical trial of chemotherapy followed by a donor stem cell transplant for infants with certain gene changes.

• A clinical trial of combination chemotherapy and targeted therapy with a tyrosine kinase inhibitor.

Standard treatment of ALL in older children and teenagers may include the following:

• Combination chemotherapy using stronger doses of anticancer drugs than those used for young children.

• A clinical trial of a new chemotherapy regimen.

• A clinical trial studying a new anticancer drug, the doses of certain anticancer drugs, and the use of radiation therapy to the brain.

Standard treatment of Philadelphia chromosome-positive childhood ALL may include the following:

• Combination chemotherapy followed by stem cell transplant using stem cells from a donor.

• Combination chemotherapy followed by targeted therapy with a tyrosine kinase inhibitor (imatinib mesylate).

• A clinical trial of combination chemotherapy and a new tyrosine kinase inhibitor.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with T-cell childhood acute lymphoblastic leukemia and Philadelphia chromosome positive childhood precursor acute lymphoblastic leukemia. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.

Recurrent Childhood Acute Lymphoblastic Leukemia

Standard treatment of recurrent childhood acute lymphoblastic leukemia (ALL) for leukemia that comes back in the bone marrow may include the following:

• Combination chemotherapy.

• Chemotherapy with or without total-body irradiation followed by a stem cell transplant, using stem cells from a donor.

Standard treatment of recurrent childhood acute lymphoblastic leukemia (ALL) for leukemia that comes back outside the bone marrow may include the following:

• Chemotherapy and radiation therapy for cancer that comes back in the testicles only.

• Combination chemotherapy and intrathecal chemotherapy with radiation therapy to the brain and/or spinal cord for cancer that comes back in the brain and spinal cord only.

Some of the treatments being studied in clinical trials for recurrent childhood ALL include the following:

• New anticancer drugs and new combination chemotherapy treatments.

• Combination chemotherapy and new kinds of targeted therapies.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent childhood acute lymphoblastic leukemia. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.

To Learn More About Childhood Acute Lymphoblastic Leukemia

For more information from the National Cancer Institute about childhood acute lymphoblastic leukemia, see the following:

• What You Need To Know About? Leukemia

• Drugs Approved for Acute Lymphoblastic Leukemia

• Understanding Cancer Series: Blood Stem Cell Transplants

• Bone Marrow Transplantation and Peripheral Blood Stem Cell Transplantation

• Targeted Cancer Therapies

• Understanding Cancer Series: Targeted Therapies

For more childhood cancer information and other general cancer resources from the National Cancer Institute, see the following:

• What You Need to Know About? Cancer

• Childhood Cancers

• CureSearch for Children's Cancer

• Late Effects of Treatment for Childhood Cancer

• Adolescents and Young Adults with Cancer

• Young People with Cancer: A Handbook for Parents

• Care for Children and Adolescents with Cancer

• Understanding Cancer Series: Cancer

• Cancer Staging

• Coping with Cancer: Supportive and Palliative Care

• Cancer Library

• Information for Survivors/Caregivers/Advocates

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Changes to This Summary (12/15/2011)

The PDQcancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Changes were made to this summary to match those made to the health professional version.

About PDQ

PDQ is a comprehensive cancer database available on NCI's Web site.

PDQ is the National Cancer Institute's (NCI's) comprehensive cancer information database. Most of the information contained in PDQ is available online at NCI's Web site. PDQ is provided as a service of the NCI. The NCI is part of the National Institutes of Health, the federal government's focal point for biomedical research.

PDQ contains cancer information summaries.

The PDQ database contains summaries of the latest published information on cancer prevention, detection, genetics, treatment, supportive care, and complementary and alternative medicine. Most summaries are available in two versions. The health professional versions provide detailed information written in technical language. The patient versions are written in easy-to-understand, nontechnical language. Both versions provide current and accurate cancer information.

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Editorial Boards made up of experts in oncology and related specialties are responsible for writing and maintaining the cancer information summaries. The summaries are reviewed regularly and changes are made as new information becomes available. The date on each summary ("Date Last Modified") indicates the time of the most recent change.

PDQ also contains information on clinical trials.

A clinical trial is a study to answer a scientific question, such as whether one treatment is better than another. Trials are based on past studies and what has been learned in the laboratory. Each trial answers certain scientific questions in order to find new and better ways to help cancer patients. During treatment clinical trials, information is collected about the effects of a new treatment and how well it works. If a clinical trial shows that a new treatment is better than one currently being used, the new treatment may become "standard." In the United States, about two-thirds of children with cancer are treated in a clinical trial at some point in their illness.

Listings of clinical trials are included in PDQ and are available online at NCI's Web site. Descriptions of the trials are available in health professional and patient versions. For additional help in locating a childhood cancer clinical trial, call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

The PDQ database contains listings of groups specializing in clinical trials.

The Children's Oncology Group (COG) is the major group that organizes clinical trials for childhood cancers in the United States. Information about contacting COG is available on the NCI Web site or from the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).