Acute Lymphoblastic Leukemia (ALL)

What is acute lymphoblastic leukemia?

Acute lymphoblastic leukemia (ALL), sometimes called acute lymphocytic leukemia, is the most common form of leukemia found in children, accounting for about 30 percent of all pediatric cancer. There are about 3,000 cases of ALL in children and youth up to age 21 each year in the United States. ALL has one of the highest cure rates of all childhood cancers.

Acute lymphoblastic leukemia affects the immature forms of white blood cells, called lymphocytes. There are two basic types of lymphocytes, B-lymphocytes and T-lymphocytes, and their immature forms are the source of the two corresponding subsets of ALL, T-ALL and B- or pre-B ALL.

The job of lymphocytes is to identify and destroy foreign proteins in the body, such as bacteria and viruses. In ALL, the bone marrow makes too many immature lymphocytes (called lymphoblasts) that do not mature correctly. Immature blood cells (blasts) do not have the ability to fight infection. The lymphoblasts overproduce and crowd out normal blood-forming cells in the bone marrow.

Signs and symptoms

The most common signs and symptoms of acute lymphoblastic leukemia in children are:

  • Anemia. Anemia occurs when normal red blood cells can't be produced because the bone marrow is overcrowded by leukemia cells. The anemic child may be more tired, take more naps, look pale, and her heart may be racing. The number of red blood cells on a blood count (expressed as "hemoglobin" or "hematocrit") will be below normal.
  • Bleeding and/or bruising. When the bone marrow cannot produce enough platelets, bleeding can occur, especially when the platelet numbers are less than 10-20,000/mm3. Low platelets can cause a child to bruise or bleed more easily.
  • Bone and joint pain. Pain in bones and joints is usually a result of the bone marrow being crowded with leukemic blasts. This is often mistaken for "growing pains."
  • Recurrent fevers/infections. The child with leukemia often shows non-specific symptoms of infection such as fever and fatigue. Although the blood count of a child with leukemia may show a high number of white blood cells, these cells are immature and do not normally fight infection. As a result, the child may have difficulty recovering from an ordinary childhood infection or may develop unusual infections.
  • Abdominal pain. Leukemia cells can collect in the kidneys, liver and spleen, causing enlargement of these organs which can cause pain in the abdomen. This pain may lead to loss of appetite and weight loss.
  • Swollen lymph nodes. Lymph nodes filter the blood. Leukemia cells often collect in the nodes, causing swelling. Swelling occurs in lymph nodes in the neck, under the arms, in the groin and chest. Sometimes it is difficult to distinguish the lymph nodes of leukemia from those that are a normal part of the body's response to infection or allergy.
  • Difficulty breathing. In leukemia, especially T-cell ALL, cells can clump together in the thymus a gland under the breastbone and around the throat. This mass of cells can cause difficulty breathing. Any wheezing, coughing and/or labored or painful breathing requires immediate medical attention.

Diagnosis

The diagnosis of acute lymphoblastic leukemia in children is based on a complete medical history and physical examination and on the following diagnostic tests:

  • Complete blood count (CBC). Blood drawn through the arm or an IV is used to look at the white blood cell number, as well as platelets. Blood tests may be done to evaluate the liver and kidneys and how the blood is clotting. 
  • Bone marrow aspirate and biopsy. Bone marrow aspirates and biopsies involve inserting a needle into a bone in the pelvis or spine and removing about 2 teaspoons of marrow for examination. Bone marrow studies require pain medicine and usually sedation or general anesthesia.
  • Lumbar puncture (spinal tap). Spinal taps involve inserting a needle into the lower back, between the bones of the spinal column or backbone, to remove the fluid that surrounds the brain and spinal cord. The same needle can be used to insert medicines to prevent or treat leukemia in the brain or spinal cord (intrathecal chemotherapy).
  • Chest X-ray. Chest X-rays are taken to see if there is a mass of cells in the thymus that may affect breathing.

Treatment

Treatment for acute lymphoblastic leukemia usually begins by addressing the signs and symptoms your child has such as anemia, bleeding and/or infection. In addition, treatment for leukemia will include most of the following:

  • Chemotherapy. Chemotherapy refers to medicines that help fight cancer. They are given by mouth, in the vein, in the muscle or under the skin. 
  • Intrathecal medications/chemotherapy. Intrathecal chemotherapy is chemotherapy that is injected into the spinal fluid to prevent or treat leukemia in the brain and spinal cord. Intrathecal medications/chemotherapy involves inserting medications through a needle into the fluid-filled space surrounding the spinal cord.
  • Blood transfusions. Blood transfusions are used for patients who have anemia who cannot make their own red blood cells. Platelets are commonly transfused when platelet counts are low. Chemotherapy causing anemia and low platelets often requires transfusions.
  • Antibiotics. Antibiotics are used to prevent or treat infections.
  • Placement of permanent line. When a central venous line is used to take blood or give medication, a plastic tube or catheter is inserted into a large vein in the chest, neck or arm. The use of a central line prevents a lot of needle sticks. 
  • Radiation therapy. Radiation therapy uses high-energy waves such as x-rays to kill or shrink cancer cells. It is rarely used to treat leukemia in the central nervous system or other places such as the eye or the testes.
  • Blood and marrow transplantation. Blood and marrow transplantation consists of three steps: 1) collection of healthy stem cells from a donor without cancer or from the patient himself or herself; 2) administration of high doses of chemotherapy and possibly radiation therapy to kill any remaining leukemia cells; and 3) infusion of the healthy stem cells through an intravenous line to produce normal blood-forming cells. Bone marrow or stem cell transplantation is commonly used to treat ALL that has not responded to chemotherapy, or that was found to have very high risk of relapse.

Treatment stages

Treatment of acute lymphoblastic leukemia takes months or years and takes place in three or more stages.

Induction

Induction refers to the first month or so of treatment in which a combination of chemotherapeutic drugs is given to reduce the numbers of leukemia cells from visible to not visible under the microscope. The goal in this stage of treatment is to reduce the number of leukemia cells in the marrow to a minimum and to make room for the return of the normal red blood cells, white blood cells and platelets. When this happens, the leukemia is said to be in "remission." 

Consolidation

In ALL, consolidation involves one or two months of drug treatment. During this phase, the rare remaining leukemia cells are targeted. The patient receives weekly spinal taps to prevent leukemia from going to the brain/spinal fluid.

Interim maintenance

Patients receive methotrexate in combination with other chemotherapy agents. In some protocols the methotrexate has to be given as an inpatient.

Intensification

In ALL, intensification involves repeating chemotherapy combinations similar to those used in induction and consolidation several months later. This stage is slightly more intensive and about half of patients get admitted to the hospital for fever, infection or other side effects.

Maintenance

This treatment stage involves repeated courses of less intense chemotherapy every 28 days for an additional 2 to 3 years. Monthly outpatient visits are required to determine response to treatment, detect any recurrent disease and manage any side effects of the treatment.

Clinical trials

The Cancer Immunotherapy Program offers several clinical trials available to qualified patients with acute lymphoblastic leukemia.

Late effects/cancer survivorship

Some children treated for acute lymphoblastic leukemia may develop complications years later. Our Cancer Survivorship Program provides information about the potential long-term effects of the specific treatment your child received, including ways of monitoring and treating these effects.

Reviewed by Susan R. Rheingold, MD


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