Leukemia - Acute Lymphocytic - ALLLast Updated: February 06, 2012 This section has been reviewed and approved by the Cancer.Net Editorial Board, 11/10 Overview
Leukemia is a cancer of the blood. Leukemia begins when normal blood cells change and grow uncontrollably. 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 begins and gets worse quickly; patients with ALL usually need immediate treatment. ALL is most common in young children and adults older than 50, but people of any age can develop ALL. About lymphocytes Lymphocytes are made 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 people with ALL, new lymphocytes do not develop into mature cells, but stay 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. About 85% of people with ALL have the B-cell subtype and about 15% have the T-cell type. The NK-cell subtype is quite rare. About ALL In people with ALL, the abnormal cells crowd other types of cells in the bone marrow, preventing the production of red blood cells (which carry oxygen), other types of white blood cells, and platelets (parts of the blood needed for clotting). This means that people with ALL may be anemic (because they do not have enough red blood cells), more likely to get infections (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. Unlike other types of cancer, 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. This section is about ALL in adults. Read about childhood ALL. Looking for More of an Overview? If you would like additional introductory information, explore these related items on Cancer.Net:
Or, choose “Next” (below, right) to continue reading this detailed section. Find out more about basic cancer terms used in this section. Statistics
This year, an estimated 6,050 people of all ages (3,450 men and boys and 2,600 women and girls) in the United States will be diagnosed with ALL. About one-third of these will be adults. ALL is much more common in children. An estimated 1,440 deaths (820 men and boys and 620 women and girls) will occur this year; about three-fourths of these deaths will be among adults. The five-year survival rate (percentage of people who survive at least five years after the cancer is detected, excluding those who die from other diseases) of people with ALL is 67%. It is important to note that survival depends on several factors, including biologic features of the disease and the age of the person. Cancer survival statistics should be interpreted with caution. These estimates are based on data from thousands of people with 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 intervals, they may not represent advances made in the treatment or diagnosis of this cancer. Learn more about understanding statistics. Statistics adapted from the American Cancer Society’s publication, Cancer Facts & Figures 2012 and the ACS website. Medical Illustrations
Risk Factors
A risk factor is anything that increases a person’s chance of developing cancer. 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. Children younger than 15 and adults older than 50 are more likely to develop ALL. Race. White people are somewhat more likely than black people to develop ALL for reasons that are not understood. Genetic disorders. People with Down syndrome, ataxia telangiectasia, Li-Fraumeni syndrome, Klinefelter syndrome, Fanconi anemia, Wiskott-Aldrich syndrome, and Bloom 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 likely to develop ALL. Viruses. Occasionally, 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 genetic research has shown that many young children who develop ALL may have had the disease before they were born, although it may take many years before the disease develops and causes symptoms. More research is being done to try to understand this finding in more detail. Symptoms
People with ALL may experience the following symptoms or signs. 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 or sign on this list, please talk with your doctor.
Diagnosis
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:
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 people with ALL but can also be a sign of other medical problems. In addition, the blood may be examined under a microscope to determine if there are lymphoblasts or other abnormal cells in the blood. Bone marrow biopsy. If the blood test shows abnormalities in the number or appearance of the white blood cells, a bone marrow biopsy will be done. In a bone marrow biopsy, the doctor takes a sample of marrow with a needle, usually from the back of the hipbone. 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 find out 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 (see below). Flow cytometry and cytochemistry (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 order of a cell’s chromosomes (long pieces of DNA that contain genes). People 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 moved to another chromosome. These changes can be seen under a microscope using special methods. About 20% to 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, in this specific instance, 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 bond together to make one 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, and chemotherapy (see Treatment) may be given in the CSF. Doctors generally give an anesthetic to numb the lower back before the procedure. Imaging tests. A computed 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 Classification) to ALL since the disease has usually spread throughout the bone marrow and blood at the time of diagnosis. These tests may not be done for every patient. Learn more about what to expect when having common tests, procedures, and scans. Find out more about common terms used during a diagnosis of cancer. Classification
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 (see Diagnosis) distinguishes between ALL involving T cells or B cells. About 5% of people with the B-cell type have a unique subtype called Burkitt leukemia or Burkitt lymphoma. ALL can also be described 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. As described in Diagnosis, about 20% to 30% of adults with ALL have a genetic abnormality or mutation called the Philadelphia chromosome, causing two genes, BCR and ABL, to become one gene called BCR-ABL. This mutation is found only in the blood-forming cells, not in other organs of the body, and is not inherited. Therefore, there is no concern about an increased risk to other family members. The BCR-ABL gene causes cells in the bone marrow to produce an abnormal enzyme that allows specific types of white blood cells called B lymphoblasts to grow out of control. It is important to test for the presence of the Philadelphia chromosome because this could influence both the prognosis and the type of treatment that is recommended. 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 numbers of white blood cell, red blood cell, and platelets. The bone marrow contains abnormal lymphoblasts, and the person usually has symptoms (listed 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. The numbers of white blood cell, red blood cell, and platelet are normal. Recurrent/refractory. Recurrent leukemia has come back after being in remission. Refractory leukemia means that the disease has not responded to treatment. 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, see the Clinical Trials section. Descriptions of the most common treatment options for ALL are listed below. Chemotherapy Chemotherapy is the use of drugs to kill cancer cells. Systemic chemotherapy is delivered through the bloodstream, targeting cancer cells throughout the body. Chemotherapy is given by a medical oncologist, a doctor who specializes in treating cancer with medication, or a hematologist, a doctor who specializes in treating blood disorders. Some people may receive chemotherapy in their doctor's office or outpatient clinic; others may go to the hospital. A chemotherapy regimen (schedule) usually consists of a specific number of cycles given over a specific time. Patients with ALL receive several different drugs throughout their treatment, 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 therapy. This stage of treatment 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, stop symptoms of the disease, and restore normal blood counts. The goal of induction therapy is a complete remission (CR), which means that the blood counts have returned to normal, the leukemia is not visible when a marrow sample is examined under the microscope, and the signs and symptoms related to the ALL are gone. More than 95% of children and 75% to 80% of adults with ALL have a CR. However, it is known that small amounts of leukemia remain, and it is necessary to give additional therapy to prevent the ALL from coming back. Consolidation therapy. This stage of 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 stage of 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 stage of therapy is used to treat ALL if it 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 (see below) 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 monitored closely as outpatients. Hospitalization is sometimes needed to give consolidation therapy, but patients are generally treated 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 tissue 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. 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 needed as well. 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 problems with blood clotting, and cause fatigue by lowering the number of red blood cells, which carry oxygen. Chemotherapy may affect fertility (ability to have a child in the future) and increase the risk of developing a second cancer. Learn more about chemotherapy and preparing for treatment. 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 by using searchable drug databases. Targeted therapy Targeted therapy is a treatment that targets specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. It is sometimes recommended in addition to standard chemotherapy, especially for Philadelphia chromosome-positive ALL (Ph+ ALL). Such drugs include imatinib (Gleevec), dasatinib (Sprycel), and nilotinib (Tasigna) for Philadelphia chromosome-positive ALL, and nelarabine (Arranon) for the treatment of T-cell ALL. Learn more about targeted treatments. Radiation therapy Radiation therapy is the use of high-energy x-rays or other particles to kill cancer cells. A doctor who specializes in giving radiation therapy to treat cancer is called a radiation oncologist. A radiation therapy regimen usually consists of a specific number of treatments given over a specific time. For ALL, radiation therapy to the brain is sometimes used to kill cancerous cells around the brain and spinal column. Side effects from radiation therapy may include fatigue, mild skin reactions, upset stomach, and loose bowel movements. Most side effects go away soon after treatment is finished. Learn more about radiation therapy. Stem cell transplantation/bone marrow transplantation 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). However, AUTO transplants are generally 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; your health care team will search a computer registry to look for a match. In addition, stem cells from umbilical cord blood are sometimes used if family donors are not available. Often, umbilical cord blood from two donors is needed for larger adults. 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. AUTO transplants are typically not used to treat ALL. 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, and they need to follow certain safety guidelines provided by their doctor to help avoid infections. 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 preventive drugs. Learn more about 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 stem cell 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 stem cell transplant is often offered to patients whose leukemia has come back. Find out more about common terms used during cancer treatment. Clinical Trials Resources
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. The clinical trial may be evaluating a new drug, a new combination of existing treatments, a new approach to radiation therapy or surgery, or a new method of 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. Sometimes people have concerns that, by participating in a clinical trial, they may receive no treatment by being given a placebo or a “sugar pill”. The use of placebos in cancer clinical trials is rare. When a placebo is used in a study, it is done with the full knowledge of the participants. Find out more about placebos in cancer clinical trials. To join a clinical trial, patients must participate in a 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. For specific topics being studied for ALL, learn more in the Current Research section. Side Effects
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. Learn more about the most common side effects of cancer and different treatments, along with ways to prevent or control them. In addition to physical side effects, you may experience psychosocial (emotional and social) effects as well. Learn more about the importance of addressing such needs, including concerns about managing the cost of your cancer care. Learn more about late effects or long-term side effects by reading the After Treatment section or talking with your doctor. After Treatment
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. It’s very important for people in remission to 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. ASCO offers cancer treatment summary forms to help keep track of the cancer treatment you received and develop a survivorship care plan once treatment is completed. 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. Find out more about common terms used after cancer treatment is complete. Current Research
ALL research is ongoing. The following advances may still be under investigation in clinical trials and may not be approved or available at this time. Most cancer centers are actively involved in clinical trials aimed at increasing the rate of cure from ALL. Always discuss all diagnostic and treatment options with your doctor. New drugs and treatment regimens. Studies are looking at the use of new chemotherapy, as well as different schedules and doses of current drugs. The drug clofarabine (Clofarex, Clolar) is being studied for adults with ALL. The drug is currently approved to treat children with recurrent ALL. In addition, several studies have shown that adolescents and younger to middle-aged adults benefit from the more intensive treatments most often used for younger children with ALL. Immunotherapy. Immunotherapy (also called biologic therapy) is designed to boost the body’s natural defenses to fight the cancer. It uses materials either made by the body of in a laboratory to bolster, target, or restore immune system function. Researchers are studying the use of different antibodies directed against ALL cells. Stem cell/bone marrow transplantation. Different ways to make stem cell transplantation (see Treatment) safer and easier are also being studied. Tests to better find ALL. Researchers are studying molecular or immunologic tests that can help find small amounts of ALL in patients in remission. Looking for More about Current Research? If you would like additional information about the latest areas of research regarding leukemia, explore these related items:
Or, choose “Next” (below, right) to continue reading this detailed section. Questions to Ask the Doctor
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:
Patient Information Resources
In addition to Cancer.Net, there are other sources of information about this type of cancer available online. Cancer.Net maintains a list of national, not-for-profit organizations that may be helpful in finding additional information, services, and support. As always, be sure to talk with your doctor about questions you may have about information you find about this disease. View organizations that offer information on this specific type of cancer. |
