Childhood Acute Lymphoblastic Leukaemia

• Childhood acute lymphoblastic leukaemia (ALL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell).
• Exposure to radiation and family history 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 leukaemia (ALL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell).

Childhood acute lymphoblastic leukaemia (also called acute lymphocytic leukaemia 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 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 leukaemic 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.

This summary is about acute lymphoblastic leukaemia. Refer to the following summaries for information on other types of leukaemia:

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

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

Possible risk factors for ALL include the following:

• Having a brother or sister with leukaemia.
• 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 or by other conditions. 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:
o The number of red blood cells and platelets.
o The number and type of white blood cells.
o The amount of haemoglobin (the protein that carries oxygen) in the red blood cells.
o The portion of the sample made up of red blood cells.
• Bone marrow aspiration and biopsy: The removal of a small piece of bone and bone marrow by inserting a needle into the hipbone or breastbone. A pathologist views the bone and bone marrow samples 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 looked at under a microscope to find out if there are 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 produces 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 depend on:

• Age and white blood cell count at diagnosis.
• How quickly and how low the white blood cell count drops after initial treatment.
• Gender and race.
• Whether the leukaemia cells began from the B lymphocytes or the T lymphocytes.
• Whether there are certain changes in the chromosomes of lymphocytes.
• Whether the leukaemia has spread to the brain and spinal cord.

Stages of Childhood Acute Lymphoblastic Leukaemia

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.
• 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 leukaemia (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 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.

Recurrent Childhood Acute Lymphoblastic Leukaemia

Recurrent childhood ALL is cancer that has recurred (come back) after it has been treated. The leukaemia 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 leukaemia (ALL).
• Children with ALL should have their treatment planned by a team of doctors with expertise in treating childhood leukaemia.
• The treatment of childhood ALL usually has 3 phases.
• Three types of standard treatment are used:
o Chemotherapy
o Radiation therapy
o Chemotherapy with stem cell transplant

• Other types of treatment are being tested in clinical trials.

There are different types of treatment for childhood acute lymphoblastic leukaemia (ALL).

Different types of treatment are available for children with acute lymphoblastic leukaemia (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 leukaemia.

Your child's treatment will be managed by a paediatric oncologist, a doctor who specializes in treating children with cancer. The paediatric oncologist may refer you to other paediatric doctors who have experience and expertise in treating children with leukaemia and who specialize in certain areas of medicine. These may include the following specialists:

• Haematologist.
• Medical oncologist.
• Paediatric surgeon.
• Radiation oncologist.
• Endocrinologist.
• Neurologist.
• Neuropathologist.
• Neuroradiologist.
• Paediatric nurse specialist.
• Social worker.
• Rehabilitation specialist.
• Psychologist.

Regular follow-up exams are very important. Side effects can result from treatment long after it ends. Radiation therapy to the head may affect the child's developing brain and may cause second cancers, especially brain tumours. Early diagnosis and treatment of these secondary brain tumours may help lower the risk from these brain tumours.

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 leukaemia cells in the blood and bone marrow. This puts the leukaemia into remission.
• Consolidation/intensification therapy: This is the second phase of therapy. It begins once the leukaemia is in remission. The purpose of consolidation/intensification therapy is to kill any remaining leukaemia 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 leukaemia 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.

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 leukaemia 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 leukaemia cells in the CNS and are given to kill the leukaemia 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 the cells 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 in the spinal column (intrathecal), a body cavity such as the abdomen, or an organ, the drugs mainly affect cancer cells in those areas. 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. 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 for storage. 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.

Other types of treatment are being tested in clinical trials.

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

Treatment Options for Childhood Acute Lymphoblastic Leukaemia

Untreated Childhood Acute Lymphoblastic Leukaemia

Standard treatment of childhood acute lymphoblastic leukaemia (ALL) during the induction, consolidation/intensification, and maintenance phases includes the following:

• Combination chemotherapy.
• Intrathecal chemotherapy with or without radiation therapy to the brain.

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

• A clinical trial of new combination chemotherapy treatments.
• A clinical trial of intrathecal chemotherapy with or without low-dose radiation therapy to the brain.

Information about these and other clinical trials is available from the NCI Web site.
Recurrent Childhood Acute Lymphoblastic Leukaemia

Standard treatment of recurrent childhood 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.

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.