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  1. Basics
  2. Risk Factors
  3. Symptoms
  4. Diagnosis
  5. Treatment

Acute lymphocytic leukemia (also called acute lymphoblastic leukemia or ALL) is a malignancy that arises in lymphocytes, white blood cells that battle infectious agents throughout the body.

Leukemia is cancer that originates in the bone marrow, the soft, spongy inner portion of certain bones, and in which the malignant cells are white blood cells (leukocytes).

Leukemia develops when a leukocyte undergoes a transformation into a malignant cell -- one capable of uncontrolled growth. Leukemia cells begin to multiply in the marrow, and as they do so they crowd out the normal blood cells -- those that carry oxygen to the body's tissues, fight infections, and help wounds heal by clotting the blood. Leukemia can also spread from the marrow to other parts of the body, including the lymph nodes, brain, liver, and spleen.

Leukemia is ten times more common among adults than among children. Leukemias are evenly split between the acute and chronic forms, but among children one form -- acute lymphocytic leukemia -- accounts for about two-thirds of cases. Acute myeloid leukemia and chronic lymphocytic leukemia are the most common types in adults.

Blood cell development begins in the marrow with the formation of stem cells. These primitive cells are capable of developing into any kind of blood cell. The first step in this evolution, or differentiation, is into one of two slightly more mature types of stem cells: lymphocytic progenitor cells and myeloid progenitor cells. These cells then undergo further specialization. Lymphocytic stem cells mature into either T cells, B cells, or natural killer cells. Myeloid stem cells mature into erythrocytes (red blood cells); platelets (which clot the blood); monocytes (a type of white blood cell); or granulocytes (a group of white blood cells that includes neutrophils, basophils, and eosinophils). Each of these types of cell has a very specific job in the functioning of the body.

A malignant transformation can happen at any stage of blood cell development. The leukemia cells that result carry many characteristics of the cell from which they began. Most leukemias fall into one of two general groups: myeloid leukemia and lymphocytic leukemia. Physicians also classify leukemias according to whether they are acute or chronic. In acute leukemias, the malignant cells, or blasts, are immature cells that are incapable of performing their immune system functions. The onset of acute leukemias is rapid, and, in most cases, fatal unless the disease is treated quickly. Chronic leukemias develop in more mature cells, which can perform some of their duties but not well. These abnormal cells also increase at a slower rate, so the disease develops more slowly than in acute leukemia, and in many cases is more difficult to cure.

Risk factors for different types of cancer are those traits that increase the likelihood that an individual will develop disease. Risk factors include certain kinds of behavior such as smoking, inherited (genetic) traits, and exposure to cancer-causing agents in the environment. There is only a very small chance that a person who has one of the few known risk factors for ALL will develop the disease.

People who are exposed to high doses of radiation (from the explosion of an atomic bomb, working in an atomic weapons plant, or a nuclear reactor accident) have a heightened risk of developing leukemia. This is also true of people who are exposed over long periods of time in the workplace to high levels of solvents such as benzene.

People who have a myelodysplastic syndrome -- a preleukemia condition -- or who have rare genetic syndromes such as Down's syndrome, Fanconi's anemia, ataxia-telangiectasia, and Bloom's syndrome have a higher risk of developing leukemia.

Many people with one or more of these risk factors never develop leukemia. And most of the people who do develop ALL have no risk factors at all. Scientists do know that most leukemias are associated with specific gene mutations -- alterations in the DNA of the diseased cells -- but, in most cases, it is not clear what causes those mutations.

The symptoms of acute leukemia generally appear suddenly and can be similar to those of a virus or flu. They can be severe enough that they prompt patients see their physicians shortly after their onset, and include:

  • fever, headache
  • loss of weight and/or appetite
  • easy bruising and/or bleeding
  • weakness and fatigue
  • coughing, shortness of breath
  • frequent minor infections or poor healing of minor cuts
  • swollen lymph nodes, stomach, head, arms, and gums
  • tiny red spots in the skin
  • bone or joint pain
  • difficulty maintaining balance
  • blurred vision
  • seizures, vomiting
  • an enlarged, painless testicle

These symptoms are associated with a wide range of conditions and illnesses. But if these problems persist, consult a physician.

Physicians perform an array of tests to help diagnose leukemia and determine its type and specific subtype. The tests help determine if there are changes in the amounts of different kinds of circulating blood cells, if the cells have an abnormal appearance when seen through a microscope, if there are changes in the cellular makeup of the bone marrow, to determine what changes have taken place in the genetic and molecular makeup of the diseased cells, and to discover any other factors that are helpful in deciding on the most effective course of treatment.

Blood tests can show whether the amounts of various components of blood are within normal ranges. In leukemia, red blood cell, platelet, and white blood cell levels may be diminished.

Bone marrow aspirates and biopsies are used to determine the number of blasts, or immature cells, in the marrow, and to uncover other features of the leukemic cells. Normally, blasts account for less than 5 percent of bone marrow content. In patients with leukemia, blasts increase to between 30 and 100 percent of marrow. In a bone marrow biopsy, physicians use a hollow needle inserted into the hipbone to remove a small piece of bone and marrow for examination. In a bone marrow aspirate, a small sample of liquid bone marrow is withdrawn through a syringe.

If diseased cells are found through the bone marrow biopsy or aspirate, physicians will also perform a lumbar puncture, or spinal tap, in which they take a sample of cerebrospinal fluid, which surrounds the brain and spinal cord -- the central nervous system (CNS), to see if the disease has spread there.

In addition, physicians use a number of tests that help them determine specific features of the cells in biopsied tissue including genetic abnormalities such as chromosomal rearrangements -- which are common in leukemias -- and whether the cells have specific proteins called antigens; this information helps both identify the cells' origins and determine the patient's prognosis. These tests include the following:

  • Cytogenetic studies to determine chromosome changes in cells
  • Immunohistochemistry studies, in which antibodies are used to distinguish between types of cancer cells
  • flow cytometry, in which prepared cells are passed through a laser beam for analysis
  • molecular genetic studies, highly sensitive DNA and RNA tests to determine specific genetic traits of cancer cells.

Physicians sometimes use imaging tests to determine whether ALL has affected the bones or the organs such as the kidneys or brain, or the lymph nodes. These tests can include chest x-rays, ultrasound, computed tomography (CT scan), and magnetic resonance imaging (MRI).

Physicians devise a course of treatment for each ALL patient that takes a number of factors into consideration: the ALL subtype; whether the patient has been treated already, with what, and how successfully; the number of leukemic cells detectable in the blood; which chromosomal alterations are present; and the patient's age and overall health. For this reason, ALL patients with the same disease subtype may receive different treatments.

The standard treatment approaches for adult leukemia are chemotherapy, immunotherapy, and bone marrow transplantation. Radiation therapy -- treatment with high-energy rays that destroy cancer cells -- is sometimes used for leukemia in the central nervous system or testicles and for pain caused by bone destruction. But because leukemia is systemic, surgery is almost always ineffective.

Treatment for ALL is typically divided into three phases:

  • Remission Induction
  • Remission Continuation (consolidation, intensification),
  • Maintenance

Remission Induction

The goal of the remission induction phase is to induce a remission, a state in which there is no visible evidence of disease and blood counts are normal. Patients may receive a combination of drugs during this phase including vincristine, prednisone, L-asparaginase, doxorubicin, daunorubicin, or cyclophosphamide. Treatment can last up to four weeks, and patients may need to be hospitalized during remission induction therapy.

Remission Continuation (Consolidation, Intensification)

In the second phase, the continuation, consolidation, or intensification phase, patients may receive high doses of chemotherapy, which are designed to eliminate any remaining leukemic cells. During this phase, treatment may include a combination of two or more of the agents 6-mercaptopurine, methotrexate, vincristine, prednisone, cytarabine, doxorubicin, daunorubicin, mitoxantrone, etoposide, ifosfamide, and cyclophosphamide.


During the third phase, the maintenance phase, patients may receive lower doses of drugs but for long periods of time -- up to two years. The goal of this phase is to destroy any stray leukemia cells that have evaded the agents used in the remission induction and consolidation stages; these cells may not be detectable by laboratory tests. Commonly used drugs for maintenance include methotrexate, 6-mercaptopurine, vincristine, and prednisone.


Physicians may include immunotherapeutic drugs throughout the course of treatment. These agents are designed stimulate the patient's own immune system to recognize and attack the leukemic cells. Immunotherapy agents include interferon alpha, which occurs naturally in the body, and monoclonal antibodies, which are genetically engineered proteins designed to target specific sites (antigens) on the surface of tumor cells. Monoclonal antibodies may be able to destroy diseased cells directly, or they may be used in a "conjugated" form, with radioisotopes (radioactive substances that radiate tumor cells), drugs, or toxins designed to destroy tumor cells attached to it.


It is not uncommon for ALL to spread to the central nervous system (CNS) -- the brain and the spinal cord. This occurs more frequently among patients who have the ALL subtype L3. Treatment to prevent or control CNS involvement is included in most patients' treatment regimen. To prevent spread of the disease to the CNS, physicians may administer chemotherapy intrathecally -- directly through the spinal column into the fluid that bathes the spinal cord and brain. Alternatively, patients may receive high-dose systemic chemotherapy or cranial irradiation -- radiation therapy to the head -- to prevent the spread of disease to the CNS.

Bone Marrow Transplant

A stem cell or bone marrow transplant is an option for some ALL patients; this procedure is done after an initial remission is achieved. In this procedure, bone marrow or stem cells -- blood-forming cells -- are filtered from the patient's (autologous transplantation) or a donor's (allogeneic transplantation) marrow or bloodstream and then frozen. The patient then receives a high dose of chemotherapy or radiotherapy, which destroys tumor cells but also damages the stem cells in the patient's bone marrow. The harvested stem cells or marrow are then administered, or transplanted, to help rebuild the patient's immune system.

New, highly sensitive laboratory tests can now probe for minimal residual disease -- the very few leukemia cells that may remain in the body after treatment ends -- in patients with certain specific types of leukemia. With the information derived from such tests, physicians can chart out further treatment options for leukemia patients.

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