Acute lymphocytic leukemia (ALL) is a cancer of the lymphocytes, a type of white blood cell involved in the body’s immune system. ALL is also called acute lymphoid leukemia or acute lymphoblastic leukemia. Acute means that the disease appears and advances quickly; patients with ALL usually require immediate treatment. ALL is most common in young children and adults older than 50, but it can occur at any age.
Lymphocytes are produced in the bone marrow, the spongy, red tissue in the inner part of the large bones. Lymphocytes are found in the blood, lymph nodes, and spleen. Healthy lymphocytes fight bacterial and viral infections. In patients with ALL, new lymphocytes do not develop into mature cells, but remain as immature cells called lymphoblasts. There are three different types of lymphocytes: T cells, B cells, and natural killer (NK) cells. Generally, T cells fight infections by activating other cells in the immune system and by destroying infected cells, B cells make antibodies, and NK cells fight microbial cells and cancer cells. Approximately 85% of ALL cases are the B-cell subtype, and about 15% are of T-cell type. The NK-cell subtype is rare.
In patients with ALL, the abnormal cells crowd other types of cells in the bone marrow, preventing the production of red blood cells, otherotherother types of white blood cells, and platelets (blood components needed for clotting). This means that patients with ALL may be anemic (because they do not have enough red blood cells), susceptible to infection (because they do not have enough of the type of white blood cells called neutrophils that fight bacteria), and bruise or bleed easily (because of a low level of platelets). Lymphoblasts may also collect in a person’s lymph tissues and cause swelling of the glands. Some cells may invade other organs, including the brain, liver, spleen, or the testicles in men.
The spread of ALL to other parts of the body does not mean the cancer is in an advanced stage, because acute leukemia is usually found throughout the body when it is diagnosed.
In 2008, an estimated 5,430 people of all ages (3,220 males and 2,210 females) in the United States will be diagnosed with ALL. Of these, 1,010 will be adults. ALL is much more common in children; ALL accounts for 72% of childhood leukemia cases. An estimated 1,460 deaths (800 males and 600 females) will occur in 2008; two-thirds of these deaths will be among adults.
The five-year relative survival rate (percentage of patients who survive at least five years after the cancer is detected, excluding those who die from other diseases) of adult patients with ALL is around 30%. It is important to note that survival depends on several factors, including biologic features of the disease and the age of the patient.
Cancer survival statistics should be interpreted with caution. These estimates are based on data from thousands of cases of this type of cancer in the United States each year, but the actual risk for a particular individual may differ. It is not possible to tell a person how long he or she will live with ALL. Because the survival statistics are measured in five-year (or sometimes one-year) intervals, they may not represent advances made in the treatment or diagnosis of this cancer.
Statistics adapted from the American Cancer Society’s publication, Cancer Facts & Figures 2008.
A risk factor is anything that increases a person’s chance of developing cancer. Some risk factors can be controlled, such as smoking, and some cannot be controlled, such as age and family history. Although risk factors can influence the development of cancer, most do not directly cause cancer. Some people with several risk factors never develop cancer, while others with no known risk factors do. However, knowing your risk factors and communicating them to your doctor may help you make more informed lifestyle and health-care choices.
The cause of ALL is not known. In general, ALL is most likely to affect children and older adults. The following factors may raise a person’s risk of developing ALL:
Age. The incidence of ALL is highest in children younger than 15 and adults older than 50.
Race. White people are somewhat more likely than black people to develop ALL.
Genetic disorders. People with Down syndrome, ataxia telangiectasia, Li-Fraumeni syndrome, Klinefelter’s syndrome, Fanconi’s anemia, Wiskott-Aldrich syndrome, and Bloom’s syndrome are at higher risk for ALL than the general population.
High doses of radiation. People who have been exposed to high levels of radiation, such as long-term survivors of atomic bombs, may be more susceptible to ALL.
Viruses. Uncommonly, ALL or unique types of lymphoma can be associated with prior viral infections, such as human T-cell leukemia virus-1 or Epstein-Barr virus.
Exposure to electromagnetic fields or high voltage electric lines has not been proven to increase a person’s risk of ALL.
Lastly, recent sophisticated genetic studies have shown that in many young children with ALL, the ALL may have been present before birth, although it may take many years before the disease develops and causes symptoms. Further research is underway to try to understand this finding in more detail.
People with ALL may experience the following symptoms. Sometimes, people with ALL do not show any of these symptoms. Or, these symptoms may be caused by a medical condition that is not cancer. If you are concerned about a symptom on this list, please talk with your doctor.
Fatigue
Weakness
Easy bruising or bleeding
Weight loss
Fever
Bone or abdominal pain
Dyspnea (difficulty breathing) or shortness of breath
Doctors use many tests to diagnose cancer and learn more about the disease. Some tests may also determine which treatments may be the most effective. For most types of cancer, a biopsy is the only way to make a definitive diagnosis of cancer. If a biopsy is not possible, the doctor may suggest other tests that will help make a diagnosis. Imaging tests may also be used. Your doctor may consider these factors when choosing a diagnostic test:
Age and medical condition
The type of cancer suspected
Severity of symptoms
Previous test results
The following tests may be used to diagnose ALL:
Blood tests. If the doctor believes a person has ALL based on the symptoms, he or she will examine the levels of different types of cells in the patient’s blood through a test called a complete blood count (CBC). Low levels of red blood cells and platelets and high levels of white blood cells are common in ALL but can also be a sign of other medical problems. In addition, a blood smear may be examined under a microscope to determine if lymphoblasts or other abnormal cells are present.
Bone marrow biopsy. If the blood test shows too many white blood cells, a bone marrow biopsy will be done. In a bone marrow biopsy, the doctor takes a sample of marrow, usually from the back of the hipbone, with a needle. The patient is given medication to numb the area beforehand. The cells from the marrow, along with the cells from the blood, are then examined under a microscope to determine the type of leukemia. The pathologist (a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease) may use this bone marrow sample for other tests, such as cytogenetics and immunophenotyping.
Flow cytometry andcytochemistry (immunophenotyping). In these tests, cancer cells are treated with chemicals or dyes that provide information about the leukemia and its subtype. ALL cells have distinctive markers (cell surface proteins) on their surface. The pattern of these markers is called the immunophenotype. These tests are used to distinguish ALL from other types of leukemia, which can also involve lymphocytes. Both tests can be done from a blood sample.
Cytogenetics. Cytogenetics is the analysis of the number and arrangement of a cell’s chromosomes (long pieces of DNA that contain genes). Patients with ALL may have specific chromosomal changes, including the addition or loss of certain chromosomes, as well as translocations, which means that parts of one chromosome have been transferred to another chromosome. These changes can be seen under a microscope using special techniques.
About 30% of adults with ALL have a change in their chromosomes called the Philadelphia chromosome. The Philadelphia chromosome is an example of a translocation, which means that genetic material from chromosome 9 breaks off and attaches to chromosome 22. In this way, two specific genes called BCR and ABL are brought together and form a single fusion gene called BCR-ABL. Some people may have other types of translocations. For example, many children with ALL have a translocation between chromosomes 12 and 21. These genes are called TEL and AML1. This information helps doctors decide which treatment is best.
Lumbar puncture(spinal tap). A lumbar puncture is a procedure in which a doctor takes a sample of cerebral spinal fluid (CSF) to look for cancer cells, blood, or tumor markers (substances found in higher than normal amounts in the blood, urine, or body tissues of people with certain kinds of cancer). Because ALL tends to spread to the CSF surrounding the brain, spinal taps are done regularly during the treatment of ALL. Doctors generally give an anesthetic to numb the lower back before the procedure.
Imaging tests. Acomputed tomography (CT or CAT) scan (test that creates a three-dimensional picture of the inside of the body) or magnetic resonance imaging (MRI, test that uses magnetic fields, not x-rays, to produce detailed images of the body) may be used to learn more about the cause of symptoms or to help diagnose infections in patients with ALL. They are not regularly used for assigning a classification (see below) to ALL since the disease is usually spread throughout the bone marrow and blood at the time of diagnosis. The use of these tests for evaluating the ALL depends on particular clinical findings in individual patients.
To help plan treatment and predict prognosis (chance of recovery), doctors classify ALL based on the type of lymphocytes that are affected (such as T cells or B cells). For example, flow cytometry distinguishes between ALL involving T cells or B cells. About 5% of the B-cell cases have a unique subtype called Burkitt leukemia or Burkitt lymphoma. ALL can also be characterized by the appearance of the cells under the microscope (called L1, L2, and L3), although this is less important than the results of the flow cytometry or cytogenetic studies. Some specific chromosomal or genetic changes in the cancer cells are used to help predict how well the disease will respond to treatment and may guide the treatment choices.
In a cancer where a solid tumor forms, doctors agree on a set of stages that describe how big the tumor is and where it has spread. Because leukemia usually does not form a solid tumor and is found throughout the body, there is no formal staging system for ALL. Instead, there are general classifications used to describe ALL:
Untreated. A patient has abnormal white blood cell, red blood cell, and platelet counts. The bone marrow contains abnormal lymphoblasts, and the person usually has symptoms as described in the Symptoms section.
In remission. A patient has received treatment for ALL. The bone marrow contains less than 5% blasts, and the patient has no symptoms. White blood cell, red blood cell, and platelet counts are back in the normal range.
Recurrent/refractory. Recurrent leukemia has come back after being in remission. Refractory leukemia means that the disease has not responded to treatment.
The treatment of ALL depends on its classification and the patient’s overall health. In many cases, a team of doctors will work with the patient to determine the best treatment plan.
This section outlines treatments that are the standard of care (the best treatments available) for this specific type of cancer. Patients are also encouraged to consider clinical trials as a treatment option when making treatment plan decisions. A clinical trial is a research study to test a new treatment to prove it is safe, effective, and possibly better than standard treatment. Your doctor can help you review all treatment options. For more information, visit the Clinical Trials section.
Chemotherapy
Chemotherapy is the use of drugs to kill cancer cells. Systemic chemotherapy is delivered through the bloodstream, targeting cancer cells throughout the body. Patients with ALL receive several different drugs throughout their treatment period, some of which are given orally (by mouth) as a pill, while others are injected into a vein (intravenously, IV). A patient may receive chemotherapy during different stages of treatment:
Induction. This stage refers to the initial course of treatment given during the first three to four weeks. It is designed to destroy most of the detectable leukemia cells, eliminate symptoms of the disease, and restore normal blood counts.
Complete remission(CR). A CR is accomplished in more than 95% of children and 75% to 80% of adults with ALL. However, it is known that small amounts of leukemia persist, and it is necessary to give additional therapy to prevent the ALL from coming back.
Consolidation therapy. This therapy refers to the use of different drugs given in doses similar to the high doses used to achieve remission. Depending on the subtype of the ALL, the doctor may recommend several courses of consolidation therapy.
Maintenance therapy. This therapy refers to treatment given both orally and intravenously over a two-year to three-year period to keep the ALL from returning. These drugs are usually given in lower doses and have fewer side effects.
Re-induction chemotherapy. This therapy is used to treat ALL that has come back after treatment.
Central nervous system prophylaxis(preventive treatment). This treatment involves the use of drugs, given directly in the spinal fluid by spinal tap and/or by vein, to prevent the leukemia from spreading from the blood to the brain or spinal cord. This treatment is often given in combination with radiation therapy to the head.
Side effects of chemotherapy and supportive treatment
Induction therapy usually begins in the hospital and often requires a hospitalization of three to four weeks. However, depending on the circumstances, many patients can leave the hospital and are followed closely as outpatients. Hospitalization is sometimes needed to give consolidation therapy, but patients are generally followed as outpatients thereafter. Maintenance therapy rarely requires hospitalization; many patients with ALL can return to school or work while receiving maintenance therapy.
Because chemotherapy attacks rapidly dividing cells, including those in normal tissues such as the hair, lining of the mouth, intestines, and bone marrow, patients receiving chemotherapy may lose their hair, develop mouth sores, or have nausea and vomiting. Chemotherapy may lower the body’s resistance to infection by reducing the number of neutrophils, lead to increased bruising and bleeding because of the decrease in the number of platelets and other disturbances in blood clotting, and cause fatigue by lowering the number of red blood cells, which carry oxygen. Chemotherapy may affect fertility (ability to conceive a child or maintain a pregnancy) and increase the risk of developing a second cancer.
Because of changes in the blood counts, most patients require transfusions of red blood cells and platelets at some point during their treatment. Treatment with antibiotics to prevent or treat infection is usually required as well.
Targeted therapy
In addition to standard chemotherapy, targeted therapy is part of treatment for some subtypes of ALL. Targeted therapy is a treatment that targets faulty genes or proteins that contribute to cancer growth and development. Imatinib (Gleevec) is used for the treatment of Philadelphia chromosome-positive ALL, while dasatinib (Sprycel) is approved for use in patients with imatinib-resistant ALL. In addition, nelarabine (Arranon) is approved for the initial treatment of T-cell ALL, and pegaspargase (Oncaspar) is approved for treatment of newly-diagnosed patients with ALL.
The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications prescribed for you, their purpose, and their potential side effects or interactions with other medications. Learn more about your prescriptions through the Drug Information Resources, which provides links to searchable drug databases.
Radiation therapy
Radiation therapy is the use of high-energy x-rays or other particles to kill cancer cells. In ALL, radiation therapy to the brain is sometimes used to kill cancerous cells around the brain and spinal column. Radiation therapy may cause fatigue, nausea, diarrhea or constipation, mild skin reactions, headache, upset stomach, and hair loss. Most side effects go away once treatment is finished.
A stem cell transplant is a medical procedure in which diseased bone marrow is replaced by highly specialized cells, called hematopoietic stem cells. Hematopoietic stem cells are found both in the bloodstream and in the bone marrow. Today, this procedure is more commonly called a stem cell transplant, rather than bone marrow transplant, because blood stem cells are typically what is being transplanted, not the actual bone marrow tissue.
There are two types of stem cell transplantation depending on the source of the replacement blood stem cells: allogeneic (ALLO) and autologous (AUTO). AUTO transplants are not used to treat ALL.
In an ALLO transplant, stem cells are obtained from a donor whose tissue matches the patient’s on a genetic level; this testing is called HLA-typing. Most often, a patient’s brother or sister serves as the donor, although unrelated donors can serve as the donor too. Millions of people worldwide have volunteered to donate stem cells for patients who do not have matched family members; matches can be made by searching a computer registry. In addition, stem cells derived from umbilical cord blood are sometimes used if family donors are not available.
In an AUTO transplant, the patient’s own stem cells are used. The stem cells are obtained from the patient when he or she is in remission from previous treatment. The stem cells are then frozen until they are needed after the high-dose treatment (explained below) is completed.
In both types, the goal of transplantation is to destroy cancer cells in the marrow, blood, and other parts of the body and have replacement blood stem cells create healthy bone marrow. In most stem cell transplants, the patient is treated with high doses of chemotherapy and/or radiation therapy to destroy as many cancer cells as possible. This also destroys the patient’s bone marrow tissue and suppresses the patient’s immune system so that, in an ALLO transplant, the donor cells are not rejected by the body. After the high-dose treatment is given, blood stem cells are infused into the patient’s vein to replace the bone marrow and restore normal blood counts from donor cells. Sometimes, ALLO transplants can also be performed after giving lower doses of chemotherapy and/or radiation therapy that are still sufficient to suppress the immune system and allow growth of the donor cells. (These transplants, sometimes termed “mini-transplants” or “reduced intensity transplants” have less immediate side effects, allowing the procedure to be used for older patients.)
Before recommending transplantation, doctors will talk with the patient about the risks of this treatment and consider several other factors, such as the type of cancer, results of any previous treatment, and patient’s age and general health.
For both ALLO and AUTO transplant types, the replacement cells engraft (begin to make new blood cells) and turn into healthy, blood-producing tissue in 10 days to three weeks. Destroying the patient’s own marrow reduces the body’s natural defenses, temporarily leaving the patient at an increased risk of infection. Until the patient’s immune system is back to normal, patients may need antibiotics and blood transfusions.
In an ALLO transplant, another major risk is that the donor’s cells will recognize the patient’s body as foreign, causing graft-versus-host disease (GVHD). GVHD may be a serious complication of allogeneic transplants and can be fatal. Other side effects may include liver problems, diarrhea, infections, and rashes. However, GVHD can also be a benefit, in that the donor cells can recognize the cancer cells as foreign and destroy these cells, a mechanism that is one of the major reasons why ALLO transplantation generally works so well over the long term. The risk of GVHD can be reduced with exact HLA-type matching and the use of preventative drugs.
In an AUTO transplant, there is no risk of GVHD because the replacement stem cells are the patient’s own cells. However, there is a risk in an autologous transplant that some of the cells that are put back into the patient could still be cancerous. Learn more by reading the Cancer.Net Feature series Understanding Bone Marrow and Stem Cell Transplantation.
Refractory/recurrent ALL
Refractory ALL occurs when a complete remission is not achieved because the drugs did not kill enough leukemia cells. Patients with refractory disease may be offered new drugs being tested in clinical trials or ALLO transplantation.
If the disease goes into remission but comes back later, it is called recurrent ALL. The treatment for recurrence depends on the length of remission. If a recurrence occurs after a long remission, the leukemia may respond again to the original treatment. If the remission was short, then other drugs are used, often in the form of new drugs being tested in clinical trials. An ALLO transplant is often offered to patients whose leukemia has come back.
Doctors and scientists are always looking for better ways to treat patients with ALL. A clinical trial is a way to test a new treatment to prove that it is safe, effective, and possibly better than a standard treatment. Patients who participate in clinical trials are among the first to receive new treatments, such as new chemotherapy before they are widely available. However, there is no guarantee that the new treatment will be safe, effective, or better than a standard treatment.
Patients decide to participate in clinical trials for many reasons. For some patients, a clinical trial is the best treatment option available. Because standard treatments are not perfect, patients are often willing to face the added uncertainty of a clinical trial in the hope of a better result. Other patients volunteer for clinical trials because they know that finding new drugs and other therapies is the only way to make progress in treating ALL. Even if they do not benefit directly from the clinical trial, their participation may benefit future patients with ALL.
To join a clinical trial, patients must complete a learning process known as informed consent. During informed consent, the doctor should list all of the patient’s options, so the person understands how the new treatment differs from the standard treatment. The doctor must also list all of the risks of the new treatment, which may or may not be different from the risks of standard treatment. Finally, the doctor must explain what will be required of each patient in order to participate in the clinical trial, including the number of doctor visits, tests, and the schedule of treatment. Learn more about clinical trials, including patient safety, phases of a clinical trial, deciding to participate in a clinical trial, questions to ask the research team, and links to find cancer clinical trials.
Cancer and its treatment can cause a variety of side effects. However, doctors have made major strides in recent years in reducing pain, nausea and vomiting, and other physical side effects of cancer treatments. Many treatments used today are less intensive but as effective as treatments used in the past. Doctors also have many ways to provide relief to patients when such side effects do occur.
Fear of treatment side effects is common after a diagnosis of cancer, but it may be helpful to know that preventing and controlling side effects is a major focus of your health-care team. Before treatment begins, talk with your doctor about possible side effects of the specific treatments you will be receiving. The specific side effects that can occur depend on a variety of factors, including the type of cancer, its location, the individual treatment plan (including the length and dosage of treatment), and the person’s overall health.
Ask your doctor which side effects are most likely to happen (and which are not), when side effects are likely to occur, and how they will be addressed by the health-care team if they do happen. Also, be sure to communicate with the doctor about side effects you experience during and after treatment. For more information on the most common side effects of cancer and different treatments, along with ways to prevent or control them, visit the section on Managing Side Effects, based on ASCO’s curriculum.
In addition to physical side effects, there may be psychosocial (emotional and social) effects as well. Learn more about the importance of addressing these needs in the section on Caring for the Whole Patient.
For more information on late effects or long-term side effects, please read the After Treatment section or talk with your doctor.
After treatment for ALL ends, talk with your doctor about developing a follow-up care plan. This plan may include regular physical examinations and/or medical tests to monitor your recovery for the coming months and years.
People in remission should receive regular follow-up examinations for several years to detect early evidence of recurrence or late effects (side effects that occur years after treatment) of chemotherapy.
People recovering from ALL are encouraged to follow established guidelines for good health, such as maintaining a healthy weight, not smoking, eating a balanced diet, and having recommended cancer screening tests. Talk with your doctor to develop a plan that is best for your needs. Moderate physical activity can help rebuild your strength and energy level. Your doctor can help you create an appropriate exercise plan based upon your needs, physical abilities, and fitness level. Learn more about Healthy Living After Cancer.
ALL research is ongoing. The following advances may still be under investigation in clinical trials and may not be approved or available at this current time. Always discuss all diagnostic and treatment options with your doctor.
The use of different antibodies directed against the ALL cells
The use of new chemotherapy or different schedules and doses of known drugs
The study of a variety of techniques to make stem cell transplantation safer and easier
The use of sophisticated molecular or immunologic tests to assess for the persistence of small amounts of ALL in patients in remission
The use of clofaribine (Clolar) in adults with ALL (this drug is approved to treat recurrent childhood ALL)
Most cancer centers are actively involved in clinical trials aimed at increasing the rate of cure from ALL. The National Cancer Institute’s Clinical Trials Cooperative Group Program sponsors many of these studies. Please talk with your doctor about these ongoing clinical trials.
Regular communication with your doctor and other caregivers is important in making informed decisions about your health care. Consider asking the following questions of your doctor:
What is my diagnosis? What does this mean?
Can you explain my pathology report (laboratory test results) to me?
What subtype of ALL do I have?
Can you recommend a leukemia specialist?
What are my options for treatment?
What clinical trials are open to me?
What treatment do you recommend? Why?
Do I need to start treatment right away?
Where is the best place for me to be treated?
What are the possible side effects of this treatment, both in the short term and the long term?
How likely is it that my ALL will go into remission?
How will the treatment affect my daily life? Will I be able to work, exercise, and perform my usual activities?
How will the treatment, especially stem cell transplantation, affect my fertility?
What follow-up tests will I need, and how often will I need them?
What support services are available to me? To my family?
American Society for Blood and Marrow Transplantation
85 W. Algonquin Rd., Ste. 550
Arlington Heights, IL 60005
Phone: 847-427-0224 www.asbmt.org
Blood and Marrow Transplant Information Network
2310 Skokie Valley Rd., Ste. 104
Highland Park, IL 60035
Toll Free: 888-597-7674
Phone: 847-433-3313 www.bmtinfonet.org
Leukemia Research Foundation
3520 Lake Ave., Ste. 202
Wilmette, IL 60091
Phone: 847-424-0600
Toll Free: 888-558-5385 www.leukemia-research.org
The Leukemia & Lymphoma Society
1311 Mamaroneck Ave., Ste.130
White Plains, NY 10605
Toll Free: 800-955-4572 www.lls.org
National Bone Marrow Transplant Link
20411 West 12 Mile Rd., Ste. 108
Southfield, MI 48076
Toll Free: 800-LINK-BMT (800-546-5268)
Phone: 248-358-1886 www.nbmtlink.org
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