21st Century Pediatric Cancer Sourcebook: Childhood Acute Lymphoblastic Leukemia (ALL) - Clinical Treatment Data with Practical Information for Patients, Families, Physicians
Edition 1.0 - February 2011
National Cancer Institute
Smashwords Edition
Copyright 2011 Progressive Management
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American Cancer Society (ACS) * http://www.cancer.org/
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PART ONE
Chapter 1A: Childhood Acute Lymphoblastic Leukemia - Patient Version
Chapter 2A: Childhood Acute Lymphoblastic Leukemia Treatment - Health Professional Version
PART TWO
Chapter 1B Late Effects of Treatment for Childhood Cancer - Patient Version
Chapter 2B: Pediatric Supportive Care
Chapter 3B: Clinical Trials Background Information
Chapter 4B: Cancer Clinical Trials -The Basic Workbook
Chapter 5B: Cancer Clinical Trials - The In-Depth Program
Chapter 6B: Clinical Trials at NIH
Chapter 7B: How To Find A Cancer Treatment Trial: A Ten Step Guide
Chapter 8B: Taking Part in Cancer Treatment Research Studies
Chapter 9B: Cancer Clinical Trials
Chapter 10B: Access to Investigational Drugs
Chapter 12B: Taking Time: Support for People with Cancer
Chapter 13B: Facing Forward - Life After Cancer Treatment
Chapter 14B: When Someone You Love Is Being Treated For Cancer
Chapter 15B: Living Beyond Cancer: Finding a New Balance
Chapter 16B: Caring for the Caregiver
Chapter 17B: Young People With Cancer, A Handbook For Parents
Chapter 18B: When Cancer Returns
Chapter 19B: When Someone You Love Has Advanced Cancer / Support for Caregivers
Chapter 20B: Chemotherapy and You
Chapter 21B: Managing Chemotherapy Side Effects - Anemia
Chapter 22B: Managing Chemotherapy Side Effects - Appetite Changes
Chapter 23B: Managing Chemotherapy Side Effects - Bleeding Problems
Chapter 24B: Managing Chemotherapy Side Effects - Constipation
Chapter 25B: Managing Chemotherapy Side Effects - Memory Changes
Chapter 26B: Managing Chemotherapy Side Effects - Mouth and Throat Changes
Chapter 27B: Managing Chemotherapy Side Effects - Nerve Changes
Chapter 28B: Managing Chemotherapy Side Effects - Pain
Chapter 29B: Managing Chemotherapy Side Effects - Skin and Nail Changes
Chapter 30B: Managing Chemotherapy Side Effects - Swelling (Fluid retention)
Chapter 31B: Targeted Cancer Therapies
Chapter 33B : Follow-up Care After Cancer Treatment
Chapter 34B: Radiation Therapy and You
Chapter 36B: Understanding Radiation Therapy, What To Know About External Beam Radiation Therapy
Chapter 37B: Radiation Therapy for Cancer
Chapter 38B: Managing Radiation Therapy Side Effects - What To Do When Your Mouth or Throat Hurts
Chapter 39B: What To Do About Hair Loss (Alopecia)
Chapter 42B: Managing Radiation Therapy Side Effects - Changes When You Urinate
Chapter 43B: Managing Radiation Therapy Side Effects What To Do About Mild Skin Changes
Chapter 45B: General Cancer Information And Resources
Chapter 46B: Cancer And The Environment - What You Need to Know, What You Can Do
Chapter 48B: FDA Warning: Beware of Online Cancer Fraud
Chapter 49B: FDA Office of Oncology Drug Products
Chapter 50B: Understanding the HIPAA Privacy Rule
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Chapter 1A: Childhood Acute Lymphoblastic Leukemia
Patient Version
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).
There are subgroups of childhood ALL.
Family history and exposure to radiation may affect the risk of developing childhood ALL.
Possible signs of childhood ALL include fever and bruising.
Tests that examine the blood and bone marrow are used to detect (find) and diagnose childhood ALL.
Certain factors affect prognosis (chance of recovery) and treatment options.
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.
Blood cell development. A blood stem cell goes through several steps to become a red blood cell, platelet, or white blood cell.
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.
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.
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 genetic disorders, 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.
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.
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) 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
Key Points for This Section
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.
There are three ways that cancer spreads in the body.
In childhood ALL, risk groups are used instead of stages.
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 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 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/µL 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/µL 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
Key Points for This Section
There are different types of treatment for childhood acute lymphoblastic leukemia (ALL).
Children with ALL should have their treatment planned by a team of doctors with expertise in treating childhood leukemia.
The treatment of childhood ALL usually has 3 phases.
Four types of standard treatment are used:
Chemotherapy
Radiation therapy
Chemotherapy with stem cell transplant
Targeted therapy
New types of treatment are being tested in clinical trials.
High-dose chemotherapy
Targeted therapy
Patients may want to think about taking part in a clinical trial.
Patients can enter clinical trials before, during, or after starting their cancer treatment.
Follow-up tests may be needed.
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. * 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.
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.
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).
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.
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. One type of targeted therapy under study for childhood ALL is monoclonal antibody therapy.
Monoclonal antibody therapy is a cancer treatment that uses antibodies made in the laboratory, from a single type of immune system cell. These antibodies can identify substances on cancer cells or normal substances that may help cancer cells grow. The antibodies attach to the substances and 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.
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.
Some of the treatments being studied in clinical trials for childhood ALL include the following:
New CNS sanctuary therapy regimens, with different combinations of anticancer drugs, with or without radiation therapy to the brain.
New regimens and different schedules of combination chemotherapy and CNS sanctuary therapy 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 donor stem 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.
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:
Targeted therapy with a monoclonal antibody.
New anticancer drugs and new combination chemotherapy treatments.
Chemotherapy without radiation therapy for cancer that comes back in the testicles only.
A lower dose of radiation therapy to the brain for cancer that comes back in the central nervous system (brain and spinal cord).
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.
Glossary Terms
acute lymphoblastic leukemia (uh-KYOOT LIM-foh-BLAS-tik loo-KEE-mee-uh)
An aggressive (fast-growing) type of leukemia (blood cancer) in which too many lymphoblasts (immature white blood cells) are found in the blood and bone marrow. Also called acute lymphocytic leukemia and ALL.
anemia (uh-NEE-mee-uh)
A condition in which the number of red blood cells is below normal.
antibody (AN-tee-BAH-dee)
A protein made by plasma cells (a type of white blood cell) in response to an antigen (a substance that causes the body to make a specific immune response). Each antibody can bind to only one specific antigen. The purpose of this binding is to help destroy the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen.
B lymphocyte (... LIM-foh-site)
A type of immune cell that makes proteins called antibodies, which bind to microorganisms and other foreign substances, and help fight infections. A B lymphocyte is a type of white blood cell. Also called B cell.
blood
A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.
blood chemistry study (blud KEH-mih-stree STUH-dee)
A procedure in which a sample of blood is examined to measure the amounts of certain substances made in the body. An abnormal amount of a substance can be a sign of disease in the organ or tissue that produces it.
blood clot
A mass of blood that forms when blood platelets, proteins, and cells stick together. When a blood clot is attached to the wall of a blood vessel, it is called a thrombus. When it moves through the bloodstream and blocks the flow of blood in another part of the body, it is called an embolus.
bone marrow (bone MAYR-oh)
The soft, sponge-like tissue in the center of most bones. It produces white blood cells, red blood cells, and platelets.
bone marrow aspiration (bone MAYR-oh AS-pih-RAY-shun)
A procedure in which a small sample of bone marrow is removed, usually from the hip bone, breastbone, or thigh bone. A small area of skin and the surface of the bone underneath are numbed with an anesthetic. Then, a special wide needle is pushed into the bone. A sample of liquid bone marrow is removed with a syringe attached to the needle. The bone marrow is sent to a laboratory to be looked at under a microscope. This procedure may be done at the same time as a bone marrow biopsy.
bone marrow biopsy (bone MAYR-oh BY-op-see)
A procedure in which a small sample of bone with bone marrow inside it is removed, usually from the hip bone. A small area of skin and the surface of the bone underneath are numbed with an anesthetic. Then, a special, wide needle is pushed into the bone and rotated to remove a sample of bone with the bone marrow inside it. The sample is sent to a laboratory to be looked at under a microscope. This procedure may be done at the same time as a bone marrow aspiration.
cancer (KAN-ser)
A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.
cell (sel)
The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.
chemotherapy (KEE-moh-THAYR-uh-pee)
Treatment with drugs that kill cancer cells.
chest x-ray
An x-ray of the structures inside the chest. An x-ray is a type of high-energy radiation that can go through the body and onto film, making pictures of areas inside the chest, which can be used to diagnose disease.
chromosome (KROH-muh-some)
Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes.
complete blood count
A test to check the number of red blood cells, white blood cells, and platelets in a sample of blood. Also called blood cell count and CBC.
cytogenetics (SY-toh-jeh-NEH-tix)
The study of chromosomes and chromosomal abnormalities.
diagnosis (DY-ug-NOH-sis)
The process of identifying a disease, such as cancer, from its signs and symptoms.
disorder (dis-OR-der)
In medicine, a disturbance of normal functioning of the mind or body. Disorders may be caused by genetic factors, disease, or trauma.
Down syndrome (...SIN-drome)
A disorder caused by the presence of an extra chromosome 21 and characterized by mental retardation and distinguishing physical features.
fluorescence in situ hybridization (floor-EH-sents in SY-too HY-brih-dih-ZAY-shun)
A laboratory technique used to look at genes or chromosomes in cells and tissues. Pieces of DNA that contain a fluorescent dye are made in the laboratory and added to cells or tissues on a glass slide. When these pieces of DNA bind to specific genes or areas of chromosomes on the slide, they light up when viewed under a microscope with a special light. Also called FISH.
gene (JEEN)
The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein.
genetics (jeh-NEH-tix)
The study of genes and heredity. Heredity is the passing of genetic information and traits (such as eye color and an increased chance of getting a certain disease) from parents to offspring.
granulocyte (GRAN-yoo-loh-SITE)
A type of immune cell that has granules (small particles) with enzymes that are released during infections, allergic reactions, and asthma. Neutrophils, eosinophils, and basophils are granulocytes. A granulocyte is a type of white blood cell. Also called granular leukocyte, PMN, and polymorphonuclear leukocyte.
groin
The area where the thigh meets the abdomen.
hemoglobin (HEE-moh-GLOH-bin)
The substance inside red blood cells that binds to oxygen in the lungs and carries it to the tissues.
immune system (ih-MYOON SIS-tem)
The complex group of organs and cells that defends the body against infections and other diseases.
immunophenotyping (IM-yoo-no-FEE-no-tie-ping)
A process used to identify cells, based on the types of antigens or markers on the surface of the cell. This process is used to diagnose specific types of leukemia and lymphoma by comparing the cancer cells to normal cells of the immune system.
infection
Invasion and multiplication of germs in the body. Infections can occur in any part of the body and can spread throughout the body. The germs may be bacteria, viruses, yeast, or fungi. They can cause a fever and other problems, depending on where the infection occurs. When the body’s natural defense system is strong, it can often fight the germs and prevent infection. Some cancer treatments can weaken the natural defense system.
laboratory test (LA-bruh-tor-ee...)
A medical procedure that involves testing a sample of blood, urine, or other substance from the body. Tests can help determine a diagnosis, plan treatment, check to see if treatment is working, or monitor the disease over time.
leukemia (loo-KEE-mee-uh)
Cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of blood cells to be produced and enter the bloodstream.
lymphoblast (LIM-foh-BLAST)
A lymphocyte that has gotten larger after being stimulated by an antigen. Lymphoblast also refers to an immature cell that can develop into a mature lymphocyte.
lymphocyte (LIM-foh-site)
A type of immune cell that is made in the bone marrow and is found in the blood and in lymph tissue. The two main types of lymphocytes are B lymphocytes and T lymphocytes. B lymphocytes make antibodies, and T lymphocytes help kill tumor cells and help control immune responses. A lymphocyte is a type of white blood cell.
lymphoid (LIM-foyd)
Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop.
malignant (muh-LIG-nunt)
Cancerous. Malignant cells can invade and destroy nearby tissue and spread to other parts of the body.
microscope (MY-kroh-SKOPE)
An instrument that is used to look at cells and other small objects that cannot be seen with the eye alone.
myeloid (MY-eh-loyd)
Having to do with or resembling the bone marrow. May also refer to certain types of hematopoietic (blood-forming) cells found in the bone marrow. Sometimes used as a synonym for myelogenous; for example, acute myeloid leukemia and acute myelogenous leukemia are the same disease.
natural killer cell (NA-chuh-rul KIH-ler sel)
A type of immune cell that has granules (small particles) with enzymes that can kill tumor cells or cells infected with a virus. A natural killer cell is a type of white blood cell. Also called NK cell and NK-LGL.
organ
A part of the body that performs a specific function. For example, the heart is an organ.
oxygen (OK-sih-jen)
A colorless, odorless gas. It is needed for animal and plant life. Oxygen that is breathed in enters the blood from the lungs and travels to the tissues.
pathologist (puh-THAH-loh-jist)
A doctor who identifies diseases by studying cells and tissues under a microscope.
petechiae (peh-TEH-kee-a)
Pinpoint, unraised, round red spots under the skin caused by bleeding.
Philadelphia chromosome (FIH-luh-DEL-fee-uh KROH-muh-some)
An abnormality of chromosome 22 in which part of chromosome 9 is transferred to it. Bone marrow cells that contain the Philadelphia chromosome are often found in chronic myelogenous leukemia.
physical examination (FIH-zih-kul eg-ZA-mih-NAY-shun)
An exam of the body to check for general signs of disease.
platelet (PLATE-let)
A tiny piece of a cell found in the blood that breaks off from a large cell found in the bone marrow. Platelets help wounds heal and prevent bleeding by forming blood clots. Also called thrombocyte.
prognosis (prog-NO-sis)
The likely outcome or course of a disease; the chance of recovery or recurrence.
protein (PRO-teen)
A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.
radiation (RAY-dee-AY-shun)
Energy released in the form of particle or electromagnetic waves. Common sources of radiation include radon gas, cosmic rays from outer space, medical x-rays, and energy given off by a radioisotope (unstable form of a chemical element that releases radiation as it breaks down and becomes more stable).
recur
To come back or to return.
red blood cell
A cell that carries oxygen to all parts of the body. Also called erythrocyte and RBC.
risk factor (... FAK-ter)
Something that increases the chance of developing a disease. Some examples of risk factors for cancer are age, a family history of certain cancers, use of tobacco products, being exposed to radiation or certain chemicals, infection with certain viruses or bacteria, and certain genetic changes.
spinal cord (SPY-nul kord)
A column of nerve tissue that runs from the base of the skull down the back. It is surrounded by three protective membranes, and is enclosed within the vertebrae (back bones). The spinal cord and the brain make up the central nervous system, and spinal cord nerves carry most messages between the brain and the rest of the body.
stem cell
A cell from which other types of cells develop. For example, blood cells develop from blood-forming stem cells.
stomach (STUH-muk)
An organ that is part of the digestive system. The stomach helps digest food by mixing it with digestive juices and churning it into a thin liquid.
symptom
An indication that a person has a condition or disease. Some examples of symptoms are headache, fever, fatigue, nausea, vomiting, and pain.
T cell
A type of immune cell that can attack foreign cells, cancer cells, and cells infected with a virus. T cells can also help control immune responses. A T cell is a type of white blood cell. Also called T lymphocyte and thymocyte.
T lymphocyte (… LIM-foh-site)
A type of immune cell that can attack foreign cells, cancer cells, and cells infected with a virus. T lymphocytes can also help control immune responses. A T lymphocyte is a type of white blood cell. Also called T cell and thymocyte.
tissue (TISH-oo)
A group or layer of cells that work together to perform a specific function.
virus (VY-rus)
In medicine, a very simple microorganism that infects cells and may cause disease. Because viruses can multiply only inside infected cells, they are not considered to be alive.
white blood cell
A type of immune cell. Most white blood cells are made in the bone marrow and are found in the blood and lymph tissue. White blood cells help the body fight infections and other diseases. Granulocytes, monocytes, and lymphocytes are white blood cells. Also called leukocyte and WBC.
x-ray
A type of high-energy radiation. In low doses, x-rays are used to diagnose diseases by making pictures of the inside of the body. In high doses, x-rays are used to treat cancer.
acute lymphoblastic leukemia (uh-KYOOT LIM-foh-BLAS-tik loo-KEE-mee-uh)
An aggressive (fast-growing) type of leukemia (blood cancer) in which too many lymphoblasts (immature white blood cells) are found in the blood and bone marrow. Also called acute lymphocytic leukemia and ALL.
aggressive (uh-GREH-siv)
In medicine, describes a tumor or disease that forms, grows, or spreads quickly. It may also describe treatment that is more severe or intense than usual.
biopsy (BY-op-see)
The removal of cells or tissues for examination by a pathologist. The pathologist may study the tissue under a microscope or perform other tests on the cells or tissue. There are many different types of biopsy procedures. The most common types include: (1) incisional biopsy, in which only a sample of tissue is removed; (2) excisional biopsy, in which an entire lump or suspicious area is removed; and (3) needle biopsy, in which a sample of tissue or fluid is removed with a needle. When a wide needle is used, the procedure is called a core biopsy. When a thin needle is used, the procedure is called a fine-needle aspiration biopsy.
blood
A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.
cell (sel)
The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.
cerebrospinal fluid (seh-REE-broh-SPY-nul FLOO-id)
The fluid that flows in and around the hollow spaces of the brain and spinal cord, and between two of the meninges (the thin layers of tissue that cover and protect the brain and spinal cord). Cerebrospinal fluid is made by tissue called the choroid plexus in the ventricles (hollow spaces) in the brain. Also called CSF.
chest x-ray
An x-ray of the structures inside the chest. An x-ray is a type of high-energy radiation that can go through the body and onto film, making pictures of areas inside the chest, which can be used to diagnose disease.
chromosome (KROH-muh-some)
Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes.
diagnosis (DY-ug-NOH-sis)
The process of identifying a disease, such as cancer, from its signs and symptoms.
leukemia (loo-KEE-mee-uh)
Cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of blood cells to be produced and enter the bloodstream.
lumbar puncture (LUM-bar PUNK-cher)
A procedure in which a thin needle called a spinal needle is put into the lower part of the spinal column to collect cerebrospinal fluid or to give drugs. Also called spinal tap.
lymph vessel (limf ...)
A thin tube that carries lymph (lymphatic fluid) and white blood cells through the lymphatic system. Also called lymphatic vessel.
lymphatic system (lim-FA-tik SIS-tem)
The tissues and organs that produce, store, and carry white blood cells that fight infections and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes, and lymphatic vessels (a network of thin tubes that carry lymph and white blood cells). Lymphatic vessels branch, like blood vessels, into all the tissues of the body.
metastasis (meh-TAS-tuh-sis)
The spread of cancer from one part of the body to another. A tumor formed by cells that have spread is called a “metastatic tumor” or a “metastasis.” The metastatic tumor contains cells that are like those in the original (primary) tumor. The plural form of metastasis is metastases (meh-TAS-tuh-SEEZ).
metastatic (meh-tuh-STA-tik)
Having to do with metastasis, which is the spread of cancer from the primary site (place where it started) to other places in the body.
microscope (MY-kroh-SKOPE)
An instrument that is used to look at cells and other small objects that cannot be seen with the eye alone.
organ
A part of the body that performs a specific function. For example, the heart is an organ.
pathologist (puh-THAH-loh-jist)
A doctor who identifies diseases by studying cells and tissues under a microscope.
physical examination (FIH-zih-kul eg-ZA-mih-NAY-shun)
An exam of the body to check for general signs of disease.
primary tumor (PRY-mayr-ee TOO-mer)
The original tumor.
solid tumor
An abnormal mass of tissue that usually does not contain cysts or liquid areas. Solid tumors may be benign (not cancer), or malignant (cancer). Different types of solid tumors are named for the type of cells that form them. Examples of solid tumors are sarcomas, carcinomas, and lymphomas. Leukemias (cancers of the blood) generally do not form solid tumors.
spinal column (SPY-nul KAH-lum)
The bones, muscles, tendons, and other tissues that reach from the base of the skull to the tailbone. The spinal column encloses the spinal cord and the fluid surrounding the spinal cord. Also called backbone, spine, and vertebral column.
stage
The extent of a cancer in the body. Staging is usually based on the size of the tumor, whether lymph nodes contain cancer, and whether the cancer has spread from the original site to other parts of the body.
testicle (TES-tih-kul)
One of two egg-shaped glands inside the scrotum that produce sperm and male hormones. Also called testis.
therapy (THAYR-uh-pee)
Treatment.
tissue (TISH-oo)
A group or layer of cells that work together to perform a specific function.
white blood cell
A type of immune cell. Most white blood cells are made in the bone marrow and are found in the blood and lymph tissue. White blood cells help the body fight infections and other diseases. Granulocytes, monocytes, and lymphocytes are white blood cells. Also called leukocyte and WBC.
x-ray
A type of high-energy radiation. In low doses, x-rays are used to diagnose diseases by making pictures of the inside of the body. In high doses, x-rays are used to treat cancer.
ALL
An aggressive (fast-growing) type of leukemia (blood cancer) in which too many lymphoblasts (immature white blood cells) are found in the blood and bone marrow. Also called acute lymphoblastic leukemia and acute lymphocytic leukemia.
blood
A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.
bone marrow (bone MAYR-oh)
The soft, sponge-like tissue in the center of most bones. It produces white blood cells, red blood cells, and platelets.
* * * * * * * * * * * *
Chapter 2A: Childhood Acute Lymphoblastic Leukemia Treatment - Health Professional Version
Last Modified: 02/04/2011
General Information About Childhood Acute Lymphoblastic Leukemia Incidence and Epidemiology * Risk Factors for Developing ALL * Overall Outcome for ALL * Cellular Classification and Prognostic Variables Clinical and Laboratory Features at Diagnosis * Leukemic Cell Characteristics * Early Response to Treatment * Prognostic Groups * Prognostic groups under clinical evaluation * Treatment Option Overview * Treatment of Newly Diagnosed ALL Induction Chemotherapy * Central Nervous System (CNS) Therapy * CNS therapy for standard-risk patients * CNS therapy for high-risk patients * Toxicity of CNS-directed therapy * Presymptomatic CNS therapy options under clinical evaluation * Current Clinical Trials * Postinduction Treatment of ALL Consolidation/Intensification Therapy * Standard-risk ALL * High-risk ALL * Very high-risk ALL * Maintenance Therapy * Treatment options under clinical evaluation * Current Clinical Trials * Postinduction Treatment for ALL Subgroups T-cell ALL * Treatment options * Treatment options under clinical evaluation * Current Clinical Trials * Infants With ALL * Treatment options * Treatment options under clinical evaluation * Adolescent Patients with ALL * Treatment options * Treatment options under clinical evaluation * Philadelphia Chromosome–Positive ALL * Treatment options * Treatment options under clinical evaluation * Current Clinical Trials * Treatment of Recurrent ALL Prognostic Factors in Recurrent ALL * Treatment of bone marrow relapse * Treatment of extramedullary relapse * Treatment Options Under Clinical Evaluation
Fortunately, cancer in children and adolescents is rare, although the overall incidence of childhood cancer has been slowly increasing since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the primary care physician, pediatric surgical subspecialists, radiation oncologists, pediatric medical oncologists/hematologists, rehabilitation specialists, pediatric nurse specialists, social workers, and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life.
Guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer have been outlined by the American Academy of Pediatrics.[2] Because treatment of children with acute lymphoblastic leukemia (ALL) entails many potential complications and requires intensive supportive care (e.g., transfusions; management of infectious complications; and emotional, financial, and developmental support), this treatment is best coordinated by pediatric oncologists and performed in cancer centers or hospitals with all of the necessary pediatric supportive care facilities. It is important that the clinical centers and the specialists directing the patient’s care maintain contact with the referring physician in the community. Strong lines of communication optimize any urgent or interim care required when the child is at home.
Dramatic improvements in survival have been achieved in children and adolescents with cancer.[1] Between 1975 and 2002, childhood cancer mortality has decreased by more than 50%. For ALL, the 5-year survival rate has increased over the same time from 60% to 89% for children younger than 15 years and from 28% to 50% for adolescents aged 15 to 19 years.[1] Childhood and adolescent cancer survivors require close follow-up because cancer therapy side effects may persist or develop months or years after treatment. (
Incidence and Epidemiology
ALL is the most common cancer diagnosed in children and represents 23% of cancer diagnoses among children younger than 15 years. ALL occurs at an annual rate of approximately 30 to 40 per million.[3,4] There are approximately 2,900 children and adolescents younger than 20 years diagnosed with ALL each year in the United States,[4] and there has been a gradual increase in the incidence of ALL in the past 25 years.[5] A sharp peak in ALL incidence is observed among children aged 2 to 3 years (>80 per million per year), with rates decreasing to 20 per million for ages 8 to 10 years. The incidence of ALL among children aged 2 to 3 years is approximately fourfold greater than that for infants and is nearly tenfold greater than that for adolescents aged 16 to 21 years. For unexplained reasons, the incidence of ALL is substantially higher in white children than in black children, with a nearly threefold higher incidence from age 2 to 3 years in white children compared with black children.[3,4] The incidence of ALL appears to be highest in Hispanic children (43 per million).[3,4]