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).
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Anatomy of the bone. The bone is made up of compact bone, spongy bone, and bone marrow. Compact bone makes up the outer layer of the bone. Spongy bone is found mostly at the ends of bones and contains red marrow. Bone marrow is found in the center of most bones and has many blood vessels. There are two types of bone marrow: red and yellow. Red marrow contains blood stem cells that can become red blood cells, white blood cells, or platelets. Yellow marrow is made mostly of fat.
ALL is the most common type of cancer in children.
Leukemia may affect red blood cells, white blood cells, and platelets.
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 myeloidstem cell or a lymphoid stem cell.
A myeloid stem cell becomes one of three types of mature blood cells:
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Blood cell development. A blood stem cell goes through several steps to become a red blood cell, platelet, or white blood cell.
In a child with ALL, too many stem cells become lymphoblasts, B lymphocytes, or T lymphocytes. These cells are also called leukemia cells. These 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, adolescents, and young adults. See the following PDQ summaries for information about other types of leukemia:
Past treatment for cancer and certain genetic conditions affect the risk of having 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:
Constitutional mismatch repair deficiency (mutations in certain genes that stop DNA from repairing itself, which leads to the growth of cancers at an early age).
Signs of childhood ALL include fever and bruising.
These and other signs and symptoms may be caused by childhood ALL or by other conditions. Check with your child's doctor if your child has any of the following:
Tests that examine the blood and bone marrow are used to diagnose childhood ALL.
The following tests and procedures may be used to diagnose childhood ALL and find out if leukemia cells have spread to other parts of the body such as the brain or testicles:
Physical exam and health 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.
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.
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Complete blood count (CBC). Blood is collected by inserting a needle into a vein and allowing the blood to flow into a tube. The blood sample is sent to the laboratory and the red blood cells, white blood cells, and platelets are counted. The CBC is used to test for, diagnose, and monitor many different conditions.
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.
Bone marrow aspiration and biopsy: The removal of bone marrow and a small piece of bone by inserting a hollow needle into the hipbone or breastbone. A pathologist views the bone marrow and bone under a microscope to look for signs of cancer.
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Bone marrow aspiration and biopsy. After a small area of skin is numbed, a bone marrow needle is inserted into the child’s hip bone. Samples of blood, bone, and bone marrow are removed for examination under a microscope.
The following tests are done on blood or the bone marrow tissue that is removed:
Cytogeneticanalysis: A laboratory test in which the chromosomes of cells in a sample of blood or bone marrow are counted and checked for any changes, such as broken, missing, rearranged, or extra chromosomes. Changes in certain chromosomes may be a sign of cancer. For example, in Philadelphia chromosome–positive ALL, part of one chromosome switches places with part of another chromosome. This is called the “Philadelphia chromosome.” Cytogenetic analysis is used to help diagnose cancer, plan treatment, or find out how well treatment is working.
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The Philadelphia (Ph) chromosome is an abnormal chromosome that is made when pieces of chromosomes 9 and 22 break off and trade places. The
ABL gene from chromosome 9 joins to the
BCR gene on chromosome 22 to form the
BCR::
ABL fusion gene. The changed chromosome 22 with the fusion gene on it is called the Ph chromosome.
Immunophenotyping: A laboratory test that uses antibodies to identify cancer cells based on the types of antigens or markers on the surface of the cells. This test is used to help diagnose specific types of leukemia. For example, the cancer cells are checked to see if they are B lymphocytes or T lymphocytes.
Lumbar puncture: A procedure used to collect a sample of cerebrospinal fluid (CSF) from the spinal column. This is done by placing a needle between two bones in the spine and into the CSF around the spinal cord and removing a sample of the fluid. The sample of CSF is checked under a microscope for signs that leukemia cells have spread to the brain and spinal cord. This procedure is also called an LP or spinal tap.
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Lumbar puncture. A patient lies in a curled position on a table. After a small area on the lower back is numbed, a spinal needle (a long, thin needle) is inserted into the lower part of the spinal column to remove cerebrospinal fluid (CSF, shown in blue). The fluid may be sent to a laboratory for testing.
This procedure is done after leukemia is diagnosed to find out if leukemia cells have spread to the brain and spinal cord. Intrathecal chemotherapy is given after the sample of fluid is removed to treat any leukemia cells that may have spread to the brain and spinal cord.
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 have formed a mass in the middle of the chest.
Certain factors affect prognosis (chance of recovery) and treatment options.
In childhood ALL, risk groups are used to plan treatment.
There are three risk groups in childhood ALL. They are described as:
Standard (low) risk: Includes children aged 1 to younger than 10 years who have a white blood cell count less than 50,000/µL at the time of diagnosis.
High risk: Includes children 10 years and older and/or children who have a white blood cell count of 50,000/µL or more at the time of diagnosis.
Very high risk: Includes children younger than age 1, children with certain changes in the genes, children who have a slow response to initial treatment, and children who have signs of leukemia after the first 4 weeks of treatment.
Other factors that affect the risk group include the following:
How quickly and how low the leukemia cell count drops after initial treatment.
Whether leukemia cells are found in the cerebrospinal fluid at the time of diagnosis.
It is important to know the risk group in order to plan treatment. Children with high-risk or very high–risk ALL usually receive more anticancer drugs and/or higher doses of anticancer drugs than children with standard-risk ALL.
Sometimes childhood ALL does not respond to treatment or comes back after treatment.
Refractory childhood ALL is cancer that does not respond to initial treatment.
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 who are experts 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:
Consolidation/intensification: This is the second phase of treatment. It begins once the leukemia is in remission. The goal of consolidation/intensification therapy is to kill any leukemia cells that remain in the body and may cause a relapse.
Maintenance: 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 during the remission induction and consolidation/intensification phases. Not taking medication as ordered by the doctor during maintenance therapy increases the chance the cancer will come back. 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 and higher doses of anticancer drugs than children with standard-risk ALL. Intrathecal chemotherapy is used to treat childhood ALL that has spread, or may spread, to the brain and spinal cord.
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. External radiation therapy uses a machine outside the body to send radiation toward the area of the body with cancer.
External radiation therapy may be used to treat childhood ALL that has spread, or may spread, to the brain, spinal cord, or testicles. It may also be used to prepare the bone marrow for a stem cell transplant.
Chemotherapy
Chemotherapy is given to kill cancer cells. In children 3 years and older, total-body irradiation is given with chemotherapy. Healthy cells, including blood-forming cells, are also destroyed by the cancer treatment. Stem cell transplant is a treatment to replace the blood-forming cells. Stem cells (immature blood cells) are removed from the blood or bone marrow of a donor and are frozen and stored. After the patient completes chemotherapy and radiation therapy, the stored stem cells are thawed and given to the patient through an infusion. These stem cells grow into (and restore) the body's blood cells.
Stem cell transplant is rarely used as initial treatment for children and adolescents with ALL. It is used more often as part of treatment for ALL that relapses (comes back after treatment).
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Stem cell transplant. (Step 1): Blood is taken from a vein in the arm of the donor. The blood flows through a machine that removes the stem cells. Then the blood is returned to the donor through a vein in the other arm. (Step 2): The patient receives chemotherapy to kill blood-forming cells. The patient may receive radiation therapy (not shown). (Step 3): The patient receives stem cells through a catheter placed into a blood vessel in the chest.
Targeted therapy
Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells. Targeted therapies usually cause less harm to normal cells than chemotherapy or radiation therapy do. There are different types of targeted therapy:
Monoclonal antibodies: Monoclonal antibodies are immune systemproteins made in the laboratory to treat many diseases, including cancer. As a cancer treatment, these antibodies can attach to a specific target on cancer cells or other cells that may help cancer cells grow. The antibodies are able to then kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells. Blinatumomab and inotuzumab are monoclonal antibodies being studied in the treatment of refractory childhood ALL. Blinatumomab is also being studied in the treatment of standard-risk ALL. Nivolumab is a monoclonal antibody being studied in the treatment of relapsed childhood ALL.
How do monoclonal antibodies work to treat cancer? This video shows how monoclonal antibodies, such as trastuzumab, pembrolizumab, and rituximab, block molecules cancer cells need to grow, flag cancer cells for destruction by the body’s immune system, or deliver harmful substances to cancer cells.
Proteasome inhibitor therapy: This treatment is a type of targeted therapy that blocks the action of proteasomes in cancer cells. Proteasomes remove proteins no longer needed by the cell. When the proteasomes are blocked, the proteins build up in the cell and may cause the cancer cell to die. Bortezomib is a type of proteasome inhibitor therapy used to treat relapsed childhood ALL. Bortezomib is also being studied in the treatment of standard-risk or high-risk patients.
New kinds of targeted therapies are also being studied in the treatment of childhood ALL.
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 (central nervous system; CNS) 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 doses of chemotherapy may not cross the blood-brain barrier to get into the fluid that surrounds the brain and spinal cord to reach the leukemia cells in the CNS, the cells are able to hide in the CNS. Systemic chemotherapy given in high doses or intrathecal chemotherapy (into the cerebrospinal fluid) is able to reach leukemia cells in the CNS. Sometimes external radiation therapy to the brain is also given.
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Intrathecal chemotherapy. Anticancer drugs are injected into the intrathecal space, which is the space that holds the cerebrospinal fluid (CSF, shown in blue). There are two different ways to do this. One way, shown in the top part of the figure, is to inject the drugs into an Ommaya reservoir (a dome-shaped container that is placed under the scalp during surgery; it holds the drugs as they flow through a small tube into the brain). The other way, shown in the bottom part of the figure, is to inject the drugs directly into the CSF in the lower part of the spinal column, after a small area on the lower back is numbed.
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 high doses of systemic chemotherapy and sometimes radiation therapy.
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 website.
Immunotherapy
Immunotherapy is a treatment that uses the patient’s immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body’s natural defenses against cancer. This cancer treatment is a type of biologic therapy.
CAR T-cell therapy: This treatment changes the patient's T cells (a type of immune system cell) so they will attack certain proteins on the surface of cancer cells. T cells are taken from the patient and special receptors are added to their surface in the laboratory. The changed cells are called chimeric antigen receptor (CAR) T cells. The CAR T cells are grown in the laboratory and given to the patient by infusion. The CAR T cells multiply in the patient's blood and attack cancer cells. CAR T-cell therapy is being studied in the treatment of childhood ALL that has relapsed (come back) a second time.
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CAR T-cell therapy. A type of treatment in which a patient’s T cells (a type of immune cell) are changed in the laboratory so they will bind to cancer cells and kill them. Blood from a vein in the patient’s arm flows through a tube to an apheresis machine (not shown), which removes the white blood cells, including the T cells, and sends the rest of the blood back to the patient. Then, the gene for a special receptor called a chimeric antigen receptor (CAR) is inserted into the T cells in the laboratory. Millions of the CAR T cells are grown in the laboratory and then given to the patient by infusion. The CAR T cells are able to bind to an antigen on the cancer cells and kill them.
Treatment for childhood acute lymphoblastic leukemia may cause side effects.
Regular follow-up exams are very important. Side effects from cancer treatment that begin after treatment and continue for months or years are called late effects.
Late effects of cancer treatment may include the following:
Physical problems, including problems with the heart, blood vessels, liver, or bones, and fertility. When dexrazoxane is given with chemotherapy drugs called anthracyclines, the risk of late heart effects is lessened.
Changes in mood, feelings, thinking, learning, or memory. Children younger than 4 years who have received radiation therapy to the brain have a higher risk of these effects.
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.
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. Information about clinical trials supported by NCI can be found on NCI’s clinical trials search webpage. Clinical trials supported by other organizations can be found on the ClinicalTrials.gov website.
Follow-up tests may be needed.
As your child goes through treatment, they will have follow-up tests or checkups. Some tests that were done to diagnose or stage the cancer may be repeated 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. These tests are sometimes called follow-up tests or check-ups.
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).
Bone marrow aspiration and biopsy is done during all phases of treatment to see how well the treatment is working.
Treatment of Childhood Acute Lymphoblastic Leukemia (Standard Risk)
Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.
Treatment of Childhood Acute Lymphoblastic Leukemia (High Risk)
Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.
Treatment of Childhood Acute Lymphoblastic Leukemia (Very High Risk)
Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.
Treatment of Childhood Acute Lymphoblastic Leukemia (Special Groups)
Treatments being studied in clinical trials for Philadelphia chromosome–positive childhood ALL include a new regimen of targeted therapy (imatinib mesylate) and combination chemotherapy with or without a stem cell transplant.
Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.
Treatment of Refractory or Relapsed Childhood Acute Lymphoblastic Leukemia
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