• Acute Lymphoblastic Leukemia (ALL)

    Acute lymphoblastic leukemia, or ALL, is a quickly progressing disease in which too many abnormal white blood cells are found in the bone marrow (the soft, spongy center of long bones). ALL accounts for about 75 to 80 percent of childhood leukemias, and 85 percent of newly diagnosed patients go on to become event-free survivors. In some cases, children who are treated for ALL and achieve an initial complete remission will have the disease return; this is known as relapsed acute lymphoblastic leukemia.

    ALL Treatment at Dana-Farber/Boston Children's

    Children and adolescents with acute lymphoblastic leukemia are treated at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center through the Leukemia Program. Continue reading to learn more about ALL or visit the Leukemia Program to learn about our expertise and treatment options for this condition.

    How common is leukemia?

    Leukemia is the most common form of cancer in children.

    • It affects about 3,000 children each year in the United States, accounting for about 30 percent of childhood cancers.
    • Leukemia can occur at any age, although it is most commonly seen in children who are between 2 and 6 years old.
    • The disease occurs slightly more frequently in males than in females, and it is more common in Caucasian children than in children of other races.

    It’s important to understand that leukemias most often occur for no known reason and in nearly all cases its cause cannot be determined. There’s nothing that you could have done or avoided doing that would have prevented the disease from developing. In the majority of childhood leukemias, gene mutations and chromosome abnormalities in the leukemia cells occur by chance. The abnormalities found in leukemia cells are not found in the other cells of the body.

    What are the different types of leukemia?

    In addition to acute lymphoblastic leukemia (ALL), there are two other types of leukemia seen in children:

    What’s the difference between ALL, AML and CML? 

    Acute lymphocytic leukemia (ALL) 

    • is also called lymphoblastic or lymphoid leukemia
    • accounts for about 80 percent of childhood leukemias
    • can occur over a short period of days to weeks
    • affects cells called lymphocytes

    Acute myelogenous leukemia 

    • is also called granulocytic, myelocytic, myeloblastic or myeloid leukemia
    • accounts for about 20 percent of childhood leukemias
    • can occur over a short period of days to weeks
    • affects cells called granulocytes (such as neutrophils or eosinophils)

    Chronic myelogenous leukemia (CML) 

    • is very uncommon in children
    • can develop over a period of months or years

    These three types all have different leukemia treatments.

    What determines what kind of leukemia my child’s has? 

    The type of leukemia (lymphoblastic or myelogenous) is determined by the type of marrow cell from which the cancer develops.

    • All blood cells start out as hematopoietic stem cells, which means they can develop into any type of blood cell. When leukemia develops from a stem cell, it is typically chronic myelogenous leukemia (CML).
    • Early on, the stem cell becomes either a lymphocyte precursor cell or a myeloid precursor cell. Acute lymphoblastic leukemia (ALL) is the type of cancer that develops from a lymphocyte precursor cell. Acute myelogenous leukemia (AML) is the type of cancer cell that develops from myeloid precursor cells.

    What are the types of ALL? 

    There are two types of lymphocytes normally found in the body:

    • B-cells (which make antibodies that fight infections)
    • T-cells (which also help fight viruses and other infections)

    The blast cells of ALL can arise from B-cell lymphocytes or T-cell lymphocytes. There are two main types of ALL: B-cell ALL and T-cell ALL. B-cell ALL is more common, especially in infants, pre-school- and school-age children. T-cell ALL tends to occur more frequently in older children and teenagers.

    What are the symptoms of ALL?

    Because leukemia is a cancer of the bone marrow, the initial symptoms often are related to abnormal bone marrow function. Bone marrow is responsible for producing the body's blood cells, including the red blood cells, white blood cells and platelets. While your child may experience symptoms differently, some of the most common include:

    • Anemia — Leukemia frequently causes anemia (low red blood cell count) because, the bone marrow becomes too crowded with leukemia cells to produce normal red blood cells. Your child may appear tired and pale, and she may breathe faster to compensate for the decrease in his cells’ ability to carry oxygen.
    • bone and joint pain — Your child may experience pain in his bones and joints. This pain is usually a result of the bone marrow being overcrowded and "full." Many children experience lower back pain or develop a limp.
    • Bruising or petechiae — When the marrow is too crowded to allow platelets to be produced, your child may bruise more easily. You might notice petechiae, or tiny red dots, on the skin if your child has a low number of platelets. These are very small blood vessels that have "leaked" or bled. While these symptoms pose no immediate risk, they do indicate the possibility of a more serious underlying problem. A blood count will show an abnormally low number of platelets.
    • Fever — Many children with ALL have fevers that are not related to a specific infection, though sometimes fever at the time of diagnosis can be a sign of infection.
    • Recurrent infections — Although there may be an unusually high number of white blood cells on your child’s blood count, these white blood cells aren't mature and don’t fight infection. Your child may have had several viral or bacterial infections over the past few weeks and may show symptoms of an infection, such as a fever, runny nose and cough.
    • Abdominal pain — Stomachaches also may be a symptom of leukemia. Leukemia cells can collect in your child’s kidney, liver and spleen, causing these organs to become enlarged. Pain in the abdomen may cause your child to lose her appetite and lose weight.
    • Swollen lymph nodes — Your child also may have swelling in the lymph nodes under the arms, in the groin, chest and neck. Leukemia cells may collect in the nodes, causing swelling.
    • Dyspnea (difficulty breathing) — In some cases of ALL, leukemia cells tend to clump together and form a mass in the middle of the chest. This chest mass can cause pain and difficulty breathing in your child. Wheezing, coughing and/or painful breathing requires immediate medical attention.

    ALL can cause a variety of symptoms in children based on their age and their disease type. Keep in mind that the symptoms of ALL may resemble other, more common conditions or medical problems. Always consult your child's physician for a diagnosis. 

    How is acute lymphoblastic leukemia diagnosed?

    Your child’s physician may order a number of different tests to determine whether your child has ALL and what type of ALL your child has. In addition to a physical examination and history, some of these may include:

    • Complete blood count (CBC) — A CBC is a blood test that measures the number and type of blood cells in your child’s blood.
    • Bone marrow aspiration and biopsy — Marrow may be removed by aspiration or a biopsy under local anesthesia. This test is performed by placing a needle through the bone (most often, one or both of the hip bones) to the marrow space to get a sample. The sample is examined under the microscope to determine the type of cells seen in the marrow. This test is necessary to make the diagnosis of leukemia.
    • Spinal tap/lumbar puncture — A special needle is placed into the lower back, between the back bones (vertebral bodies) into the spinal canal. A small amount of cerebral spinal fluid (called CSF—the fluid that surrounds a child’s brain and spinal cord) will be removed and tested to see if leukemia cells are seen under the microscope. In cases of ALL, chemotherapy is given into the spinal fluid at the same time that a lumbar puncture is done.
    • X-ray — An x-ray is a way to get a picture of bones, lungs and other organs. In ALL, this test is performed to look for a mass in the chest, which can sometimes occur and cause breathing problems.
    • Chromosome analysis — Samples of blood and bone marrow can be sent to a special laboratory to look for certain changes in the chromosomes of the leukemia cell. For example, in ALL, part of one chromosome may be moved to another chromosome, or there may be too many or too few chromosomes. The results of chromosome tests may help to determine the way the leukemia is treated.

    After we complete all necessary tests, our experts meet to review and discuss what they have learned about your child's condition. Then, we will meet with you and your family to discuss the results and outline the best treatment options for your child's leukemia.

    What is the treatment for acute lymphoblastic leukemia (ALL)?

    Your child’s physician will determine a specific course of treatment for childhood leukemia based on several factors, including:

    • your child's age, overall health and medical history
    • the type of ALL (B-cell or T-cell)
    • certain aspects of the ALL, such as the number of white blood cells in the blood when the leukemia is diagnosed, whether or not leukemia cells are seen in the spinal fluid, and whether or not specific chromosomal abnormalities are found in the leukemia cell
    • how well the leukemia responds to the first few weeks of treatment
    • your child's tolerance for certain medications, procedures or therapies
    • whether your child has Down syndrome
    • how your child's physician expects the disease to progress

    Treatment for ALL is a long-term process. Chemotherapy and other treatment for the disease may take two years or more to complete.

    There are a number of treatments that your child’s physician may recommend. Some of them help to treat the leukemia, while others are intended to address complications of the disease or side effects of the treatment. Treatment usually begins by addressing your child’s symptoms, such as anemia, bruising and/or fever. In addition, treatment may include the following (alone or in combination):

    Chemotherapy 

    Chemotherapy is a drug treatment that interferes with the cancer cell's ability to grow or reproduce. For some types of cancer, chemotherapy is used alone, while in others it is used in conjunction with other therapy, such as radiation or surgery. Chemotherapy is the standard first treatment for acute lymphoblastic leukemia (ALL).

    How is chemotherapy given to children? 

    Your child my receive chemotherapy:

    • orally, as a pill or liquid to swallow
    • intramuscularly (IM), as an injection into the muscle or fat tissue
    • intravenously (IV), directly to the bloodstream
    • intrathecally, with a needle directly into the fluid surrounding the spine

    Does chemotherapy cause side effects in children? 

    While chemotherapy can be quite effective in treating certain cancers, the medications don’t distinguish healthy cells from cancer cells. As a result, there can be side effects during treatment. Your child’s care team will work to manage or prevent these side effects whenever possible.

    What other treatments are used? 

    Radiation therapy 

    Radiation therapy uses high-energy rays (radiation) from a specialized machine to damage or kill cancer cells and shrink tumors. Radiation is usually only given if your child is at a high risk of relapse occurring in the brain or central nervous system.

    Stem cell transplant 

    A stem cell (or bone marrow) transplant is a treatment that is rarely used to treat ALL except for:

    • certain unusual subtypes of ALL
    • relapsed leukemia - if the leukemia comes back (relapse) after initial treatment with chemotherapy

    Stem cells are a specific type of cell from which all blood cells develop. They can develop into red blood cells to carry oxygen, white blood cells to fight disease and infection and platelets to aid in blood clotting. Stem cells are found primarily in bone marrow, but some also circulate in the blood stream.

    In ALL, the cells for a stem cell transplant come from donors (other people). These donated cells are used to replace your child’s stem cells after particularly intense treatment with chemotherapy and/or radiation.

    Other medications 

    We may give your child other medications to prevent or treat damage to other systems of his body caused by treatment or its side effects. Your child also may be given antibiotics to prevent or treat infections.

    What is sanctuary therapy? 

    In children with ALL, leukemia cells travel everywhere in the body, including into the brain and spinal fluid. Not all chemotherapy drugs that are given by mouth, vein or in the muscle can get into the brain effectively to treat any leukemia that is “hiding” there.

    However, it is important to treat the leukemia cells hiding in the brain and spinal fluid to prevent the leukemia from coming back. To treat the leukemia hiding in the brain and spinal fluid, your child will receive:

    • intrathecal chemotherapy – chemotherapy drugs delivered directly into the spinal canal to kill off cancerous cells that may hide in the central nervous system (CNS)

    Your child may also receive:

    • cranial radiation therapy – radiation treatment to the head to destroy leukemia cells that may have moved into the CNS

    What are the phases of ALL treatment?

    In general, stages in the treatment of acute lymphoblastic leukemia (ALL) include:

    1. Remission induction 

    Remission induction is the first stage of ALL treatment. It consists of chemotherapy given over a four-week period to clear the marrow of visible leukemia cells. The goal of this phase is to achieve complete remission, which means leukemia cells are no longer visible under a microscope when examining either the bone marrow or blood.

    The induction phase usually lasts approximately one month. Most children are in complete remission at the end of the month of treatment. If your child is not in remission after the first month (that is, leukemia cells can still be seen in the marrow under a microscope), another induction phase will be started using different chemotherapy drugs. 

    Even after remission is achieved, leukemia cells are still present in the body, which is why further therapy is necessary.

    2. Intensification or consolidation 

    Intensification or consolidation is continued treatment with chemotherapy to kill additional leukemia cells. This phase will include chemotherapy drugs given in the blood, in the vein, in the spinal fluid and sometimes in the muscle. Radiation therapy also may be given to the brain during this phase.

    3. Maintenance or continuation 

    The goal of this stage is to eradicate all leukemia from the body. Usually during this phase, less intensive chemotherapy is used, much of which can be given at home. This phase will last for many months. Your child must visit his physician regularly during this stage to determine response to treatment, detect any recurrent disease and manage any side effects of treatment.

    What is minimal residual disease (MRD)? 

    Minimal residual disease (MRD) is a term that is used for the “invisible” leukemia that is left behind after your child is in complete remission. It means that leukemia cells are still in your child's body, but there are too few of them to see them under a microscope.

    Doctors use special tests after the end of the induction phase to measure the amount of MRD remaining in a patient's marrow.

    The results of MRD tests are used to help determine the type of treatment your child’s doctor will recommend during the intensification phase of treatment. Children with higher levels of MRD at the end of induction are often given stronger chemotherapy drugs during the intensification phase to kill the remaining leukemia cells hiding in the body.

    What is the long-term outlook for ALL?

    What is the long-term outlook and prognosis for a child with leukemia?

    The prognosis for children with ALL is very positive. The five-year, event-free survival rate (which refers to survival without relapse) for children with ALL is about 85 percent. Ultimately, more than 90 percent of patients are cured of the disease.

    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
    • the subtype of leukemia
    • whether there are certain changes in the chromosomes of lymphocytes
    • whether the leukemia is seen in the spinal fluid at diagnosis

    As with any cancer, prognosis and long-term survival can vary greatly. Relapse can occur during any stage of treatment, even with aggressive therapy, or may occur months or years after treatment has ended.

    Overall, the outcomes of patients with relapsed ALL is poor. In general, relapsed ALL cells become resistant to chemotherapy drugs. Patients who relapse during or just after completing treatment may benefit from a stem cell transplant. Patients who relapse six months or more after initial treatment can often be re-treated with more intensive chemotherapy. 

    Prompt medical attention and aggressive therapy are important for the best prognosis, and continuous follow-up care is essential. New methods are continually being discovered to improve treatment and decrease side effects of the treatment for the disease.

    Long-term follow-up 

    Childhood cancer was once considered to always be fatal, but today, the majority of children diagnosed with cancer can expect to be long-term survivors.

    Survivorship comes with numerous complex issues: the long-term effects of treatment and the risk of second cancers, as well as social and psychological concerns.

    Since 1993, physicians, nurses, researchers and psychologists in our cancer survivorship program at David B. Perini, Jr. Quality of Life Clinic at Dana-Farber/Boston Children’s have helped thousands of survivors of pediatric cancers, treated at the institute and at other hospitals in New England and elsewhere, to manage these long-term consequences.

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