Childhood Acute Lymphoblastic Leukemia Treatment & Symptoms

Childhood acute lymphoblastic leukemia (ALL) facts

*Childhood acute lymphoblastic leukemia (ALL) facts medical author: Melissa Conrad Stöppler, MD

Childhood acute lymphoblastic leukemia (C-ALL) is a common type of cancer
in children. Like all leukemias, it is a cancer of blood-forming cells in the
bone marrow.
Symptoms and signs of C-ALL include
- fever,
- bruising,
- bleeding,
- weakness,
- loss of appetite, and
- painless lumps in the neck, groin, or armpits (enlarged
  lymph nodes).
Bone marrow aspiration and biopsy, cerebrospinal fluid analysis,
imaging studies, and blood counts are all tests used to diagnose C-ALL.
Results of diagnostic tests are used to establish risk groups that help plan the
best treatment for each child with C-ALL.
Treatment options include
chemotherapy, radiation therapy, stem cell transplant, and targeted therapy.
New types of treatment include CAR T-cell therapy, a type of immunotherapy that
changes the patient’s T cells (a type of immune system cell).
The majority of
children with ALL can be cured with modern treatments.

Childhood Acute Lymphoblastic Leukemia Sign

Easy bruising

A bruise is caused when tiny blood vessels are damaged or broken as the result of trauma to the skin (be it bumping against something or hitting yourself with a hammer). The raised area of a bump or bruise results from blood leaking from these injured blood vessels into the tissues as well as from the body’s response to the injury. A bruise is medically referred to as a contusion. A purplish, flat bruise that occurs when blood leaks out into the top layers of skin is referred to as an ecchymosis.

Patients with inherited clotting problems (such as in hemophilia) or acquired clotting problems (such as in patients with liver diseases like cirrhosis) can develop extensive bruising, unexplained bruising, or even life-threatening bleeding. Sometimes spontaneous bruising is a sign of a bone marrow problem.

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 ALL or acute lymphocytic leukemia) 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.

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 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. The cells do not work like normal lymphocytes and are not able to fight infection very well. These cells are cancer (leukemia) cells. 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.

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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:

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.

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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:

Being exposed to x-rays before birth.
Being exposed to radiation.
Past treatment with chemotherapy.
Having certain genetic conditions, such as:
- Down syndrome.
- Neurofibromatosis type 1.
- Bloom syndrome.
- Fanconi anemia.
- Ataxia-telangiectasia.
- Li-Fraumeni syndrome.
- 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).
Having certain changes in the chromosomes or genes.

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 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 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.
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, 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.

The following tests are done on blood or the bone marrow tissue that is removed:

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 of lymphocytes. For example, in Philadelphia chromosome-positive ALL, part of one chromosome switches places with part of another chromosome. This is called the "Philadelphia chromosome."
Immunophenotyping: A laboratory test in which the antigens or markers on the surface of a blood or bone marrow cell are checked to see if they are lymphocytes or myeloid cells. If the cells are malignant lymphocytes (cancer) they 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.
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.

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

The prognosis (chance of recovery) depends on:

How quickly and how low the leukemia cell count drops after the first month of treatment.
Age at the time of diagnosis, sex, race, and ethnic background.
The number of white blood cells in the blood at the time of diagnosis.
Whether the leukemia cells began from B lymphocytes or T lymphocytes.
Whether there are certain changes in the chromosomes or genes of the lymphocytes with cancer.
Whether the child has Down syndrome.
Whether leukemia cells are found in the cerebrospinal fluid.
The child's weight at the time of diagnosis and during treatment.

Treatment options depend on:

Whether the leukemia cells began from B lymphocytes or T lymphocytes.
Whether the child has standard-risk, high-risk, or very high-risk ALL.
The age of the child at the time of diagnosis.
Whether there are certain changes in the chromosomes of lymphocytes, such as the Philadelphia chromosome.
Whether the child was treated with steroids before the start of induction therapy.
How quickly and how low the leukemia cell count drops during treatment.

For leukemia that relapses (comes back) after treatment, the prognosis and treatment options depend partly on the following:

How long it is between the time of diagnosis and when the leukemia comes back.
Whether the leukemia comes back in the bone marrow or in other parts of the body.

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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 of 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:

Whether the leukemia cells began from B lymphocytes or T lymphocytes.
Whether there are certain changes in the chromosomes or genes of the lymphocytes.
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.

Relapsed childhood ALL is cancer that has 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.

Refractory childhood ALL is cancer that does not respond to 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:

Pediatrician.
Hematologist.
Medical oncologist.
Pediatric surgeon.
Radiation oncologist.
Neurologist.
Pathologist.
Radiologist.
Pediatric nurse specialist.
Social worker.
Rehabilitation specialist.
Psychologist.
Child-life specialist.

Children and adolescents may have treatment-related side effects that appear months or years after treatment for acute lymphoblastic leukemia.

Regular follow-up exams are very important. Treatment can cause side effects long after it has ended. These are called late effects.

Late effects of cancer treatment may include:

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.
Second cancers (new types of cancer) or other conditions, such as brain tumors, thyroid cancer, acute myeloid leukemia, and myelodysplastic syndrome.

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.

The treatment of childhood ALL usually has three phases.

The treatment of childhood ALL is done in phases:

Remission induction: 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.
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 may be used to treat childhood ALL that has spread, or may spread, to the brain and spinal cord.

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.

The way the radiation therapy is given depends on the type of cancer being treated. 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 with stem cell transplant

Stem cell transplant is a method of giving high doses of chemotherapy and sometimes total-body irradiation, 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 adolescents 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 become more white blood cells or blasts than the body needs. Imatinib mesylate is a TKI used in the treatment of children with Philadelphia chromosome-positive ALL. Dasatinib and ruxolitinib are TKIs that are being studied in the treatment of newly diagnosed high-risk ALL.

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. Blinatumomab and inotuzumab are monoclonal antibodies being studied in the treatment of refractory childhood ALL.

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 reach 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.

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.

Chimeric antigen receptor (CAR) T-cell therapy

CAR T-cell therapy is a type of immunotherapy that 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.

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.

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.

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.

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

Treatment options for childhood acute lymphoblastic leukemia

Newly diagnosed childhood acute lymphoblastic leukemia (standard risk)

The treatment of standard-risk childhood acute lymphoblastic leukemia (ALL) during the remission induction, consolidation/intensification, and maintenance phases always includes combination chemotherapy. When children are in remission after remission induction therapy, a stem cell transplant using stem cells from a donor may be done. When children are not in remission after remission induction therapy, further treatment is usually the same treatment given to children with high-risk ALL.

Intrathecal chemotherapy is given to prevent the spread of leukemia cells to the brain and spinal cord.

Treatments being studied in clinical trials for standard-risk ALL include new chemotherapy regimens.

Newly diagnosed childhood acute lymphoblastic leukemia (high risk)

The treatment of high-risk childhood acute lymphoblastic leukemia (ALL) during the remission induction, consolidation/intensification, and maintenance phases always includes combination chemotherapy. Children in the high-risk ALL group are given more anticancer drugs and higher doses of anticancer drugs, especially during the consolidation/intensification phase, than children in the standard-risk group.

Intrathecal and systemic chemotherapy are given to prevent or treat the spread of leukemia cells to the brain and spinal cord. Sometimes radiation therapy to the brain is also given.

Treatments being studied in clinical trials for high-risk ALL include new chemotherapy regimens with or without targeted therapy or stem cell transplant.

Newly diagnosed childhood acute lymphoblastic leukemia (very high risk)

The treatment of very high-risk childhood acute lymphoblastic leukemia (ALL) during the remission induction, consolidation/intensification, and maintenance phases always includes combination chemotherapy. Children in the very high-risk ALL group are given more anticancer drugs than children in the high-risk group. It is not clear whether a stem cell transplant during first remission will help the child live longer.

Intrathecal and systemic chemotherapy are given to prevent or treat the spread of leukemia cells to the brain and spinal cord. Sometimes radiation therapy to the brain is also given.

Treatments being studied in clinical trials for very high-risk ALL include new chemotherapy regimens with or without targeted therapy.

Newly diagnosed childhood acute lymphoblastic leukemia (special groups)

T-cell childhood acute lymphoblastic leukemia

The treatment of T-cell childhood acute lymphoblastic leukemia (ALL) during the remission induction, consolidation/intensification, and maintenance phases always includes combination chemotherapy. Children with T-cell ALL are given more anticancer drugs and higher doses of anticancer drugs than children in the newly diagnosed standard-risk group.

Intrathecal and systemic chemotherapy are given to prevent the spread of leukemia cells to the brain and spinal cord. Sometimes radiation therapy to the brain is also given.

Treatments being studied in clinical trials for T-cell ALL include new anticancer agents and chemotherapy regimens with or without targeted therapy.

Infants with ALL

The treatment of infants with ALL during the remission induction, consolidation /intensification, and maintenance phases always includes combination chemotherapy. Infants with ALL are given different anticancer drugs and higher doses of anticancer drugs than children 1 year and older in the standard-risk group. It is not clear whether a stem cell transplant during first remission will help the child live longer.

Intrathecal and systemic chemotherapy are given to prevent the spread of leukemia cells to the brain and spinal cord.

Treatments being studied in clinical trials for infants with ALL include the following:

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

Children 10 years and older and adolescents with ALL

The treatment of ALL in children and adolescents (10 years and older) during the remission induction, consolidation/intensification, and maintenance phases always includes combination chemotherapy. Children 10 years and older and adolescents with ALL are given more anticancer drugs and higher doses of anticancer drugs than children in the standard-risk group.

Intrathecal and systemic chemotherapy are given to prevent the spread of leukemia cells to the brain and spinal cord. Sometimes radiation therapy to the brain is also given.

Treatments being studied in clinical trials for children 10 years and older and adolescents with ALL include new anticancer agents and chemotherapy regimens with or without targeted therapy.

Philadelphia chromosome-positive ALL

The treatment of Philadelphia chromosome-positive childhood ALL during the remission induction, consolidation/intensification, and maintenance phases may include the following:

Combination chemotherapy and targeted therapy with a tyrosine kinase inhibitor (imatinib mesylate) with or without a stem cell transplant using stem cells from a donor.

Refractory childhood acute lymphoblastic leukemia

There is no standard treatment for the treatment of refractory childhood acute lymphoblastic leukemia (ALL).

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

Targeted therapy (blinatumomab or inotuzumab).
Chimeric antigen receptor (CAR) T-cell therapy.

Relapsed childhood acute lymphoblastic leukemia

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

Systemic 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.
Combination chemotherapy and radiation therapy for cancer that comes back in the testicles only.
Stem cell transplant for cancer that has recurred in the brain and/or spinal cord.

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

New anticancer drugs and new combination chemotherapy treatments.
Combination chemotherapy and new kinds of targeted therapies (blinatumomab or inotuzumab).
Chimeric antigen receptor (CAR) T-cell therapy.

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