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Acute Lymphocytic Leukemia

(ALL; Acute Lymphoblastic Leukemia)

By Michael E. Rytting, MD, Department of Leukemia, University of Texas MD Anderson Cancer Center;Department of Pediatrics, University of Texas MD Anderson Cancer

Acute lymphocytic leukemia is a life-threatening disease in which the cells that normally develop into lymphocytes become cancerous and rapidly replace normal cells in the bone marrow (see Overview of Leukemia).

  • People may have symptoms, such as fever, weakness, and paleness, because they have too few normal blood cells.

  • Blood tests and a bone marrow evaluation are usually done.

  • Chemotherapy is given and is often effective.

Acute lymphocytic leukemia (ALL) occurs in people of all ages but is the most common cancer in children, accounting for 25% of all cancers in children younger than 15 years. ALL most often affects young children between the ages of 2 and 5 years. Among adults, it is somewhat more common in people older than 45.

In ALL, very immature leukemia cells accumulate in the bone marrow, destroying and replacing cells that produce normal blood cells. The leukemia cells are carried in the bloodstream to the liver, spleen, lymph nodes, brain, and testes, where they may continue to grow and divide. However, ALL cells can accumulate anywhere in the body. They can spread to the layers of tissue covering the brain and spinal cord (leukemic meningitis) and can cause anemia, liver and kidney failure, and other organ damage.

Symptoms

Early symptoms of ALL result from the inability of the bone marrow to produce enough normal blood cells.

  • Fever and excessive sweating may indicate infection. A high risk of infection results from too few normal white blood cells.

  • Weakness, fatigue, and paleness, which indicate anemia, result from too few red blood cells. Some people may have a rapid heart rate or chest pain.

  • Easy bruising and bleeding, sometimes in the form of nosebleeds or bleeding gums, result from too few platelets.

Other symptoms occur when leukemic cells invade other organs.

  • Leukemia cells in the brain may cause headaches, vomiting, and disturbances of vision, equilibrium, hearing, and facial muscles.

  • Leukemia cells in the bone marrow may cause bone and joint pain.

  • A sense of fullness in the abdomen and sometimes pain can result when leukemia cells enlarge the liver and spleen.

Did You Know...

  • About 80% of children with acute lymphocytic leukemia are cured.

Diagnosis

  • Blood tests

  • Bone marrow examination

Blood tests, such as a complete blood count, can provide the first evidence of ALL. The total number of white blood cells may be decreased, normal, or increased, but the number of red blood cells and platelets is almost always decreased. In addition, very immature white blood cells (blasts) are often present in blood samples examined under a microscope.

A bone marrow examination is almost always done to confirm the diagnosis and to distinguish ALL from other types of leukemia. Blasts are tested for chromosome abnormalities, which helps doctors determine the exact type of the leukemia and what drugs to use to treat it.

Tests of blood and urine may also be done to detect other abnormalities related to ALL. Imaging tests may also be needed. Computed tomography (CT) or magnetic resonance imaging (MRI) is done if the person has symptoms that suggest leukemia cells in the brain. Chest x-ray may be done to check for leukemia cells in the area around the lungs. CT, MRI, or ultrasonography of the abdomen may be done when internal organs are enlarged.

Prognosis

Before treatment was available, most people who had ALL died within 4 months of the diagnosis. Now, nearly 80% of children and 30 to 40% of adults with ALL are cured. For most people, the first course of chemotherapy brings the disease under control (complete remission). Children between the ages of 3 and 9 have the best prognosis. Infants and older adults fare least well. The white blood cell count at the time of diagnosis, the response to therapy, and the chromosome abnormalities in the leukemia cells also influence outcome.

Treatment

  • Chemotherapy

Chemotherapy is highly effective and is administered in phases:

  • Induction

  • Consolidation with preventive treatment of the brain

  • Intensification

  • Maintenance

Induction chemotherapy is the initial phase of treatment. The goal of induction chemotherapy is to achieve remission by destroying leukemia cells so that normal cells can once again grow in the bone marrow. People may need to stay in the hospital for a few days or weeks, depending on how quickly the bone marrow recovers. Blood and platelet transfusions may be necessary to treat anemia and to prevent bleeding, and antibiotics may be needed to treat bacterial infections. Intravenous fluids and therapy with a drug called allopurinol may also be used to help rid the body of harmful substances, such as uric acid, that are released when leukemia cells are destroyed.

One of several combinations of drugs is used, and doses are repeated for several days or weeks. The specific combination depends on results of the diagnostic tests. One combination consists of prednisone (a corticosteroid) taken by mouth and weekly doses of vincristine (a chemotherapy drug) given with an anthracycline drug (usually daunorubicin), asparaginase, and sometimes cyclophosphamide, given intravenously. New drugs are being investigated.

The consolidation phase continues to treat bone marrow disease, but because ALL is likely to spread to the brain, it also concentrates on treating leukemia that has spread to the brain or on preventing the spread of leukemia cells to the brain. For treatment of leukemia cells in the layers of tissue covering the brain and spinal cord (the meninges), methotrexate, cytarabine, corticosteroids, or a combination are usually injected directly into the cerebrospinal fluid. This chemotherapy may be given in combination with radiation therapy to the brain.

During intensification (also called delayed intensification or interim maintenance), treatments are given to destroy any remaining leukemia cells. Additional chemotherapy drugs, or the same drugs as were used during the induction phase, may be used a few times over a period of several weeks. For some people who are at high risk of relapse because of particular chromosomal changes found in their cells, stem cell transplantation during the first remission is often recommended.

Further maintenance chemotherapy, which usually consists of fewer drugs, sometimes at lower doses, usually continues for 2 to 3 years.

Relapse

Leukemia cells may begin to appear again (a condition termed relapse), often in the blood, bone marrow, brain, or testes. Early reappearance in the bone marrow is particularly serious. Chemotherapy is given again, and although many people respond to this repeat treatment, the disease has a strong tendency to come back, especially in infants and in adults. When leukemia cells reappear in the brain, chemotherapy drugs are injected into the cerebrospinal fluid 1 or 2 times a week. When leukemia cells reappear in the testes, radiation therapy is given along with chemotherapy.

For people who have relapsed, high doses of chemotherapy drugs along with allogeneic stem cell transplantation ("allogeneic means" the stem cells are from another person) offers the best chance of cure. But transplantation can be done only if stem cells can be obtained from a person who has a compatible tissue type (human leukocyte antigen [HLA]-matched). The donor is usually a sibling, but cells from matched, unrelated donors (or occasionally partially matched cells from family members or unrelated donors, as well as umbilical stem cells) are sometimes used. Stem cell transplantation is rarely used for people older than 65 because it is much less likely to be successful and side effects are much more likely to be fatal.

New therapies using monoclonal antibodies (proteins that attach specifically to the leukemia cells, tagging them for destruction) are showing promise in people with relapsed ALL. An even newer therapy involves modifying a type of lymphocytes (T lymphocytes, also called T cells) from the person who has leukemia so that the new T cells will recognize and attack leukemia cells. So far, these modified T cells have been very promising as a new therapy for relapsed ALL.

After relapse, additional treatment for people who are unable to undergo stem cell transplantation is often poorly tolerated and ineffective, frequently causing people to feel much sicker. However, remissions can occur. End-of-life care should be considered for people who do not respond to treatment.

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