Leukemia, Acute Lymphocytic, Childhood: General Information

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

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 produces stem cells (immature cells) that develop into mature blood cells. There are 3 types of mature blood cells:

• Red blood cells that carry oxygen to all tissues of the body.
• White blood cells that fight infection and disease.
• Platelets that help prevent bleeding by causing blood clots to form.

In ALL, too many stem cells develop into a type of white blood cell called lymphocytes. These lymphocytes may also be called lymphoblasts or leukemic cells. There are 3 types of lymphocytes:

• B lymphocytes that make antibodies to help fight infection.
• T lymphocytes that help B lymphocytes make the antibodies that help fight infection.
• Natural killer cells that attack cancer cells and viruses.

In ALL, the lymphocytes are not able to fight infection very well. Also, as the number of lymphocytes 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 subgroups of childhood ALL.

Three of the subgroups of ALL are based on the type of blood cell that is affected, whether there are certain changes in the chromosomes, and age at diagnosis:

• T cell ALL.
• Philadelphia chromosome positive ALL.
• ALL diagnosed in an infant.

These subgroups are treated differently from other types of ALL.

Exposure to radiation and family history may affect the risk of developing childhood ALL.

Anything that increases your risk of getting a disease is called a risk factor. 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 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 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 or feeling tired.
• 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.

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.
• 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.

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

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.

It is important to know the risk group in order to plan treatment.

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. Clinical trials are taking place in many parts of the country. Information about ongoing clinical trials is available from the NCI Web site. Choosing the most appropriate cancer treatment is a decision that ideally involves the patient, family, and health care team.

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

Your child's treatment will be managed by a pediatric oncologist, a doctor who specializes in treating children with cancer. The pediatric oncologist may refer you to other pediatric doctors who have experience and expertise 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.
• Neuropathologist.
• Neuroradiologist.
• 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 may cause second cancers, especially brain tumors. Early diagnosis and treatment of these secondary brain tumors may help lower the risk from these brain tumors.

The treatment of childhood ALL usually has 3 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 each phase of therapy. Because chemotherapy that is given by mouth or injected into a vein may not reach leukemia cells in the CNS (brain and spinal cord), the cells are able to find “sanctuary” (hide) in the CNS. Intrathecal chemotherapy and radiation therapy 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.

Three 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 spinal column (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 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. Intrathecal chemotherapy is given in addition to chemotherapy by mouth or vein.

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.

Chemotherapy with stem cell transplant

Stem cell transplant is a method of giving chemotherapy and replacing blood-forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of a donor and are frozen and stored. After the chemotherapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These reinfused stem cells grow into (and restore) the body's blood cells. A stem cell transplant using stem cells from a donor who is not related to the patient is being studied in clinical trials.

New types of treatment are being tested in clinical trials. These include the following:

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.

Other drug therapy

Imatinib mesylate (Gleevec) is a type of anticancer drug called a tyrosine kinase inhibitor. It blocks the enzyme, tyrosine kinase, that causes stem cells to develop into more white blood cells (granulocytes or blasts) than the body needs.

• Bone marrow aspiration and biopsy: The removal of bone marrow, blood, and a small piece of bone by inserting a needle into the hipbone or breastbone. A pathologist views the bone marrow, blood, and bone under a microscope to look for signs of cancer.
  
  
• Cytogenetic analysis: A 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 ALL, part of one chromosome is moved to another chromosome. This 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.
  
  The prognosis (chance of recovery) and treatment options depend on:

• Age and white blood cell count at diagnosis.
• How quickly and how low the leukemia cell count drops after initial treatment.
• Gender and race.
• Whether the leukemia cells began from the B lymphocytes or the 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

Untreated 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/or radiation therapy to the brain.

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

• Combination chemotherapy with or without intrathecal chemotherapy. Radiation therapy to brain may also be given.
• Combination chemotherapy followed by stem cell transplant using stem cells donated by a brother or sister.

Childhood Acute Lymphoblastic Leukemia Subgroups

Standard treatment of T-cell childhood acute lymphoblastic leukemia (ALL) is usually combination chemotherapy. CNS sanctuary therapy with intrathecal chemotherapy and/or radiation therapy to the brain may also be given. One of the treatments being studied in clinical trials for T-cell childhood ALL is a new kind of anticancer drug.

Treatment of infants with ALL is usually a clinical trial of systemic chemotherapy with intrathecal chemotherapy.

Standard treatment of Philadelphia chromosome-positive childhood ALL is usually a stem cell transplant using stem cells donated by a brother or sister. One of the treatments being studied in clinical trials for Philadelphia chromosome-positive childhood ALL is imatinib mesylate (Gleevec).

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.

Standard treatment of recurrent childhood acute lymphoblastic leukemia (ALL) may include the following:

• Combination chemotherapy.
• Systemic chemotherapy and intrathecal chemotherapy with or without radiation therapy to the brain and spinal cord.
• Chemotherapy with stem cell transplant, using stem cells from a donor who is related to the patient, with or without total-body irradiation.
• Chemotherapy plus radiation therapy for cancer that recurs in the testicles only.

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

• A clinical trial of chemotherapy with stem cell transplant, using stem cells from a donor who is not related to the patient, with or without total-body irradiation.
• A clinical trial of new anticancer drugs and new combination chemotherapy treatments.

Source:  National Cancer Institute