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NCI/PDQ^® Patients: Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®)

National Cancer Institute
Last Modified: December 7, 2012

TABLE OF CONTENTS

• General Information About Childhood Acute Lymphoblastic Leukemia

• Risk Groups for Childhood Acute Lymphoblastic Leukemia

• Recurrent Childhood Acute Lymphoblastic Leukemia

• Treatment Option Overview

• Treatment Options for Childhood Acute Lymphoblastic Leukemia
  • Newly Diagnosed Childhood Acute Lymphoblastic Leukemia (Standard Risk)
  • Newly Diagnosed Childhood Acute Lymphoblastic Leukemia (High Risk)
    • T-cell childhood acute lymphoblastic leukemia
    • Infants with ALL
    • Children and teenagers with ALL
    • Philadelphia chromosome-positive ALL
  • Recurrent Childhood Acute Lymphoblastic Leukemia

• To Learn More About Childhood Acute Lymphoblastic Leukemia

• Changes to This Summary (12/07/2012)

• Get More Information From NCI

• About 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.

ALL is the most common type of cancer in children.

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

A myeloid stem cell becomes one of three types of mature blood cells:

• Red blood cells that carry oxygen and other substances to all tissues of the body.
• Platelets that form blood clots to stop bleeding.
• White blood cells that fight infection and disease.

A lymphoid stem cell becomes a lymphoblast cell and then 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 a child with ALL, too many stem cells become lymphoblasts, B lymphocytes, or T lymphocytes. These cells are cancer (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 in children, teenagers, and young adults. See the following PDQ® summaries for information about other types of leukemia:

• Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies Treatment
• Adult Acute Lymphoblastic Leukemia Treatment
• Chronic Lymphocytic Leukemia Treatment
• Adult Acute Myeloid Leukemia Treatment
• Chronic Myelogenous Leukemia Treatment
• Hairy Cell Leukemia Treatment

Family history and being exposed 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. Talk with your child's doctor if you think your child may be at risk. Possible risk factors for ALL include the following:

• Being exposed to x-rays before birth.
• Being exposed to radiation.
• Past treatment with chemotherapy.
• Having certain changes in the genes.
• Having certain genetic conditions that include the following:
  • Down syndrome.
  • Ataxia-telangiectasia.
  • Bloom syndrome.
  • Neurofibromatosis.
  • Shwachman 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. Check with your child's doctor if your child has any of the following problems:

• 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.Bone marrow aspiration and biopsy. After a small area of skin is numbed, a Jamshidi needle (a long, hollow needle) is inserted into the patient's hip bone. Samples of blood, bone, and bone marrow are removed for examination under a microscope.
• Cytogenetic analysis: A laboratory test in which the cells in a sample of blood or bone marrow are viewed under a microscope to look for certain changes in the chromosomes 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.Philadelphia chromosome. A piece of chromosome 9 and a piece of chromosome 22 break off and trade places. The bcr-abl gene is formed on chromosome 22 where the piece of chromosome 9 attaches. The changed chromosome 22 is called the Philadelphia chromosome.
• 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) depends on:

• Age at diagnosis, gender, and race.
• The number of white blood cells at diagnosis.
• Whether the leukemia cells began from B lymphocytes or T lymphocytes.
• Whether there are certain changes in the chromosomes of lymphocytes.
• Whether the child has Down syndrome.
• Whether the leukemia has spread to the brain, spinal cord, or testicles.
• How quickly and how low the leukemia cell count drops after initial treatment.

The treatment options depend on:

• Whether the leukemia cells began from B lymphocytes or T lymphocytes.
• Whether the child has standard-risk or high-risk ALL.
• The age of the child at diagnosis.
• Whether there are certain changes in the chromosomes of lymphocytes, such as the Philadelphia chromosome.

For leukemia that recurs (comes back) after initial treatment, the prognosis and treatment options 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.

Risk Groups for Childhood Acute Lymphoblastic Leukemia

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

The following tests and procedures may be used to find out if the cancer has spread:

• Lumbar puncture: A procedure used to collect cerebrospinal fluid from the spinal column. This is done by placing a needle into the spinal column. This procedure is also called an LP or spinal tap.
• 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 leukemia cells are forming a mass in the middle of the chest.
• Testicular biopsy: 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 to plan treatment.

Risk groups are described as:

• Standard (low) risk: Includes children aged 1 to younger than 10 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 10 years and older 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.
• Whether the leukemia has spread to the brain, spinal cord, testicles, or other parts of the body.

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, spinal cord, testicles, or 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 pediatric oncologist, 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.
• Neurologist.
• Pathologist.
• Radiologist.
• Pediatric nurse specialist.
• Social worker.
• Rehabilitation specialist.
• Psychologist.

Regular follow-up exams are very important. Treatment can cause side effects long after it has ended. These are called late effects. Radiation therapy to the brain may cause changes in mood, feelings, thinking, learning, or memory. Children younger than 4 years have a higher risk of side effects from radiation therapy to the brain.

Late effects of treatment for ALL also include the risk of second cancers (new types of cancer), especially brain tumors.

Some late effects may be treated or controlled. 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 three phases.

The treatment of childhood ALL is done in phases:

• Induction therapy: This is the first phase of treatment. The goal 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 goal 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. The goal 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.

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 child's risk group. Children with high-risk ALL receive more anticancer drugs, higher doses of anticancer drugs, and receive treatment for a longer time than children with standard-risk ALL.

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.

Chemotherapy with stem cell transplant

Stem cell transplant is a method of giving 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 treatment, the donor's stem cells are given to the patient through an infusion. These reinfused stem cells grow into (and restore) the patient's blood cells. The stem cell donor doesn't have to be 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 become more white blood cells 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.

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

See Drugs Approved for Acute Lymphoblastic Leukemia for more information.

Treatment is given to kill leukemia cells that have spread or may spread to the brain, spinal cord, or testicles.

Treatment to kill leukemia cells or prevent the spread of leukemia cells to the brain and spinal cord is called CNS-directed therapy. Chemotherapy may be used to treat leukemia cells that have spread, or may spread, to the brain and spinal cord. Because standard chemotherapy may not reach leukemia cells in the CNS (brain and spinal cord), the cells are able to "find sanctuary" (hide) in the CNS. Chemotherapy given in high doses or intrathecally (into the cerebrospinal fluid) is able to reach leukemia cells in the CNS. External radiation therapy may also be used to treat children and teenagers in the high risk group.

These treatments are given in addition to treatment that is used to kill leukemia cells in the rest of the body. All children with ALL receive CNS-directed therapy as part of induction therapy and consolidation/intensification therapy and sometimes during maintenance therapy.

If the leukemia cells spread to the testicles, treatment includes aggressive chemotherapy and sometimes radiation therapy.

New types of treatment are being tested in clinical trials.

Information about clinical trials is available from the NCI Web site.

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 child's condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Bone marrow biopsy and aspirates are done during all phases of treatment to see how well the treatment is working.

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 child's doctor for clinical trials that are not listed here but may be right for your child.

Newly Diagnosed Childhood Acute Lymphoblastic Leukemia (Standard Risk)

Treatment of standard-risk childhood acute lymphoblastic leukemia (ALL) during the induction, consolidation/intensification, and maintenance phases may include the following:

• Combination chemotherapy.
• Combination chemotherapy followed by stem cell transplant using stem cells from a donor.
• A clinical trial of a new chemotherapy regimen.
• A clinical trial of a new combination chemotherapy and intrathecal chemotherapy regimen given with or without radiation therapy and/or stem cell transplant. The chemotherapy dose and/or schedule depends on the patient's risk group after induction therapy.

CNS-directed therapy to treat or prevent the spread of leukemia cells to the brain and spinal cord may include the following:

• Intrathecal chemotherapy.
• High-dose systemic chemotherapy.
• Radiation therapy.
• A clinical trial of a new anticancer drug, the doses of certain anticancer drugs, and the use of radiation therapy to the brain.

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.

Newly Diagnosed Childhood Acute Lymphoblastic Leukemia (High Risk)

T-cell childhood acute lymphoblastic leukemia

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

• Combination chemotherapy.
• A clinical trial of a new chemotherapy regimen.

CNS-directed therapy to treat or prevent the spread of leukemia cells to the brain and spinal cord may include the following:

• Intrathecal chemotherapy.
• High-dose systemic chemotherapy.
• Radiation therapy.
• A clinical trial of a new anticancer drug, the doses of certain anticancer drugs, and the use of radiation therapy to the brain.

Infants with ALL

Treatment of infants with ALL may include the following:

• Combination chemotherapy.
• Chemotherapy followed by a donor stem cell transplant has been studied but it is not clear 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.

CNS-directed therapy to treat or prevent the spread of leukemia cells to the brain and spinal cord may include the following:

• Intrathecal chemotherapy.
• High-dose systemic chemotherapy.

Children and teenagers with ALL

Treatment of ALL in children and teenagers (10 years and older) may include the following:

• Combination chemotherapy.
• A clinical trial of a new combination chemotherapy regimen.
• A clinical trial of a new anticancer drug, new doses of certain anticancer drugs, and the use of radiation therapy to the brain. The chemotherapy dose and/or schedule depends on the patient's risk group after induction therapy.

CNS-directed therapy to treat or prevent the spread of leukemia cells to the brain and spinal cord may include the following:

• Intrathecal chemotherapy.
• High-dose systemic chemotherapy.
• Radiation therapy.
• A clinical trial of a new intrathecal chemotherapy and high-dose systemic chemotherapy regimen and the use of radiation therapy.

Philadelphia chromosome-positive ALL

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

• Combination chemotherapy followed by targeted therapy with a tyrosine kinase inhibitor (imatinib mesylate).
• Combination chemotherapy followed by stem cell transplant using stem cells from a donor.
• A clinical trial of combination chemotherapy and a new tyrosine kinase inhibitor, with or without stem cell transplant.

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
• Questions to Ask Your Doctor About Cancer
• Cancer Library
• Information for Survivors/Caregivers/Advocates

Changes to This Summary (12/07/2012)

The PDQ® cancer 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.

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