Leukemia - Acute Lymphoblastic - ALL - ChildhoodLast Updated: December 28, 2009 This section has been reviewed and approved by the Cancer.Net Editorial Board, 10/09 Overview
Leukemia, a cancer of the blood, is the most common type of cancer in children. Leukemia begins when normal blood cells change and grow uncontrollably. The most common type of childhood leukemia is acute lymphoblastic leukemia, also called acute lymphocytic leukemia, acute lymphoid leukemia, or ALL. When a child has ALL, the normal cells in a child’s bone marrow are overwhelmed and replaced by abnormal lymphoblasts, which are immature lymphocytes (a type of white blood cell). Normal lymphocytes fight infections in the body. However, when a child has ALL, the lymphoblasts that fill the bone marrow are abnormal and do not develop into mature cells that can produce the antibodies needed to prevent and fight infection. These abnormal lymphoblasts also crowd out other normal cells in the bone marrow, preventing the production of red blood cells, many other types of normal white blood cells, and platelets (cells that help blood to clot). If the bone marrow is not functioning correctly, the child may experience the following:
The leukemic lymphoblasts may also collect in the child’s lymph nodes and cause them to swell. Lymphoblasts may also spread to other organs, including the skin, liver, spleen, ovaries (in girls), testicles (in boys), and the spinal fluid. This section is about ALL that occurs in children, sometimes called childhood ALL or pediatric ALL. Learn more about adult acute lymphocytic leukemia. Statistics ALL is the most common type of childhood cancer. In 2009, an estimated 2,655 children, age 0 through 19, in the United States will be diagnosed with ALL. It is most common in younger children, especially children ages two through four. The five-year relative survival rate (the percentage of people who survive at least five years after the cancer is detected, excluding those who die from other diseases) of children with ALL is more than 80%. 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 childhood 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. Source: American Cancer Society Find out more about basic cancer terms used in this section. Medical Illustrations
Risk Factors
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 risk factors 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. Although doctors don’t know what causes most childhood cancers, some evidence shows that certain genetic factors may play a role in ALL. Children who are born with conditions that cause an abnormal immune system, such as Down syndrome, ataxia telangiectasia, and Bloom syndrome, may have a higher risk of developing leukemia. A child with an identical twin that develops ALL before age six has an increased risk of developing leukemia. If an identical twin develops leukemia within the first few months of life, the other twin will almost always develop the same leukemia. It is important to note, however, that for most children with leukemia, there is no known cause or risk factor Symptoms
Children with ALL often experience the following symptoms. Sometimes, children with ALL do not show any of these symptoms. Or, these symptoms may be caused by a medical condition that is not cancer. For example, the early signs of ALL can look very much like the flu or other common illnesses. When one or more of these symptoms lasts for longer than one would expect, or you are worried about a symptom on this list, please talk with your child’s doctor.
The child’s doctor may also detect an enlarged liver or spleen during a physical examination. Diagnosis
Doctors use many tests to diagnose cancer and determine if it has spread. Some tests may also determine which treatments may be the most effective. A patient history, physical examination, complete blood cell count (CBC), and bone marrow aspiration (see below) are the main procedures used to diagnose ALL, and each is used to diagnose ALL or rule out other conditions. Blood tests. A CBC provides a count of each type of cell in the blood. The blood count may also show abnormal leukemic cells. The blood count is abnormal, in some way, in nearly all children with ALL at the time of diagnosis. Bone marrow aspiration. A bone marrow aspiration is recommended if the blood test shows unusual blood counts or immature cells in the blood, or if the doctor suspects that a child may have leukemia. For this test, a sample of bone marrow is removed from the child’s hip with a needle and examined under a microscope. The child’s skin in that area will be numbed with medication beforehand. From this test, the doctor can determine whether the child has leukemia and, if so, what type of leukemia it is. The doctor or nurse will collect multiple samples of bone marrow at the same time for other tests, such as chromosome and molecular genetic analyses and immunophenotyping (see Classification). These additional tests are often extremely important to determine the treatment that is most appropriate. Lumbar puncture (spinal tap). A lumbar puncture can determine if the leukemia has spread to the spinal fluid. It is a procedure in which a doctor takes a sample of cerebral 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). CSF is the fluid that flows around the brain and the spinal cord. Doctors generally give an anesthetic to numb the lower back before the procedure. The presence or absence of leukemia in the central nervous system will help determine the most appropriate treatment. There may be times when it is appropriate to deliver medicine to treat or prevent leukemia of the central nervous system at the same time that the lumbar puncture is done. 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
While there is no staging system for pediatric ALL compared to other types of cancer, there are a number of factors that help determine the best treatment plan and determine the chance that the cancer will come back after treatment. Doctors plan treatment based on these and other factors: Age when diagnosed. Infants younger than 12 months and children age 10 and older need more intensive treatments. White blood cell counts. Children with higher white blood cell counts need more intensive treatments. Commonly, white blood cell counts are labeled as higher if they are more than 50,000 per microliter (ml). Immunophenotyping.This term refers to the profile of various proteins expressed by the leukemic cells. Knowing if the cancer cells express the proteins more closely resembling those of either normal B-cells or T-cells will help doctors plan appropriate treatment and is useful in predicting how the cancer will respond to treatment. Genetic abnormalities in the leukemic cells. Abnormal numbers of chromosomes, abnormal structural changes in a chromosome, or certain molecular genetic changes in the chromosomes of leukemic cells may affect outcome and therefore treatment. Note that the genetic changes referred to here are changes in the genetic material of the leukemic cells, not the child’s cells–most children with leukemia have completely normal genes. Response to early treatment. How the leukemia responds to the first one to four weeks of treatment (determined by examining the child’s blood or bone marrow) may predict the overall response to treatment. Recent studies have shown that some children may need more intense treatment to improve the chance of a cure. This includes those whose cancer is not responding well to early treatment or those who have high levels of residual leukemic cells (cells remaining after treatment) at the end of remission induction (see Treatment). Treatment
The following are used to describe the state of disease for children with ALL: Untreated ALL. The child hasn’t yet received any treatment. ALL in remission. There are normal levels of white and other blood cells after treatment. Physical examinations, blood counts, and bone marrow aspirates show no detectable leukemia. Remission is the absence of signs or symptoms of leukemia. Recurrent ALL. Recurrent ALL is cancer that comes back after the child has had some period of remission. The leukemia may recur in the bone marrow, spinal fluid, testicles (for boys), or, less commonly, other areas of the body. Refractory ALL. The leukemia did not go into remission, despite remission induction treatment (see below). Treatment Overview In general, cancer in children is uncommon, so it can be hard for doctors to plan treatments unless they know what has been most effective in other children. That’s why more than 60% of children with cancer are treated as part of a clinical trial. Clinical trials are research studies that compare standard treatments (the best treatments available) with newer treatments that may be more effective. Investigating new treatments involves careful monitoring using scientific methods, and all participants are followed closely to track progress. To take advantage of these newer treatments, all children with cancer should be treated at a specialized cancer center. Doctors at these centers have extensive experience in treating children with cancer and have access to the latest research. A doctor who specializes in treating children with cancer is called a pediatric oncologist. Many times, a team of doctors treats a child with cancer. Pediatric cancer centers often have extra support services for children and their families, such as nutritionists, social workers, and counselors. Special activities for kids with cancer may also be available. Three types of treatments are used to treat childhood ALL: chemotherapy, radiation treatment, and stem cell transplantation/bone marrow transplantation. Sometimes, these treatments are used in combination. Descriptions of each treatment option 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. Some people may receive chemotherapy in their doctor’s office; others may go to the hospital. A chemotherapy regimen (schedule) usually consists of a specific number of cycles given over a specific time. Chemotherapy is the primary treatment for ALL. Several drugs are used in chemotherapy for ALL. Chemotherapy may be given by mouth, injected into a vein or muscle, or injected into the CSF. It is generally done in four phases: Remission induction therapy uses chemotherapy to kill as many of the cancer cells as possible to cause the cancer to go into remission. Central nervous system directed therapy kills any cancer cells in the central nervous system and prevents the spread of the cancer to the spinal fluid. Consolidation therapy begins when the child’s cancer has gone into remission. Higher doses of chemotherapy, or drugs not used during previous treatment, are used to kill the majority of the remaining cancer cells. Continuation or maintenance therapy lasts for two to three years to kill any residual leukemia. The side effects of chemotherapy depend on the individual and the dose used, but can include fatigue, risk of infection, nausea and vomiting, loss of appetite, bone and joint damage, and diarrhea. Less commonly, chemotherapy may cause learning problems and liver dysfunction. These side effects usually go away once treatment is finished. The severity of the side effects depends on the type and amount of the drug being given and the length of time the child receives the drug. The degree to which children experience side effects may also be affected by other factors, including genetic differences in the way the medications are processed by the body, the child or teen’s age when diagnosed, and their overall health and well-being. 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 your child, their purpose, and their potential side effects or interactions with other medications. Learn more about your child’s prescriptions by using searchable drug databases. 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. The most common type of radiation treatment is called external-beam radiation therapy, which is radiation given from a machine outside the body. Radiation therapy for ALL is generally used only when the cancer has spread to the brain, spinal fluid, or a boy’s testicles, or in high-risk disease to help prevent the spread of leukemia to the spinal fluid. Radiation therapy is more often used for patients with T-cell leukemia. 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. However, long-term side effects of radiation treatment to the brain and body can occur and may potentially include learning disabilities and a risk of developing a brain tumor (see After Treatment). Learn more about radiation therapy. Stem cell transplantation/bone marrow transplantation Stem cell transplantation is most often used as a treatment for ALL after the leukemia has recurred. 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). 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, a donation of stem cells derived from umbilical cord blood is sometimes considered 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, usually after the high-dose treatment (explained below) is completed. In both types, the goal of transplantation is to prevent the cancer cells in the marrow, blood, and other parts of the body from returning. The transplant allows the patient’s marrow to be replaced with healthy blood stem cells from another source. 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 mild or serious complication of allogeneic transplants, and can even 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. In an AUTO transplant, there is little 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 about bone marrow and stem cell transplantation. Recurrent ALL Treatment for recurrent ALL depends on many factors, including the type of treatment the child received originally, the length of time between the initial diagnosis and the recurrence, and whether leukemic cells are found in the bone marrow, CSF, testicles, or in a combination of these sites at the time of recurrence. Doctors will plan treatment based on each child’s circumstances; just as for newly diagnosed patients, clinical trials typically offer the best chance of cure. Find out more about common terms used during cancer treatment. Clinical Trials Resources
Doctors and scientists are always looking for better ways to treat children 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 or prevention. Children who participate in clinical trials are among the first to receive new treatments before they are widely available. New treatments are commonly the best available therapy modified in ways that may bring about a better result. However, there is no guarantee that the new treatment will be safe, effective, or better than a standard treatment. People decide to participate in clinical trials for many reasons. For most 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 children with ALL. Even if they do not benefit directly from the clinical trial, their participation may benefit future children 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 in general, and placebos are never used in clinical trials for the treatment of children with cancer. 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, parents and children 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 childhood 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 child’s 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 child’s 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 your child experiences 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, there may be 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 child’s doctor. After Treatment
After treatment for ALL ends, talk with your child’s doctor about developing a follow-up care plan. This plan may include regular physical examinations and/or medical tests to monitor your child’s recovery for the coming months and years. All children treated for cancer, including ALL, should have life-long, follow-up care. Based on the type of treatment the child received, the doctor will determine what examinations and tests are needed to check for long-term side effects, such as learning disabilities, anxiety, bone and joint damage, and the possibility of secondary cancers. Your child’s doctor can recommend the necessary screening tests. Follow-up care should address the child’s quality of life, including any developmental or emotional concerns. Learn more about childhood cancer survivorship. For the majority of childhood ALL survivors, there are relatively few significant long-term side effects. A recent study demonstrated that patients who did not receive radiation therapy and have been in remission at least 10 years were similar to the general population in terms of rates of health-care coverage, marriage, and employment. Survivors should be sensitive to their level of functioning and level of stress, and they may need counseling if any problems arise. It is important that children with school problems undergo neuropsychological testing in order to determine the cause. Tutoring in academic subjects or providing help in achieving appropriate organizational skills is very important since many problems are correctable with help. Survivors should also be evaluated for bone or joint pain as it may be caused by treatment-related destruction of the bone. If a child did not receive radiation therapy and intensive chemotherapy with cyclophosphamide (Cytoxan, Clafen, Neosar) and/or etoposide (VePesid, Toposar), secondary cancers and infertility (the inability to have children) are rare. Future heart problems are rare, but if types of drugs called anthracyclines, such as doxorubicin (Adriamycin) or daunorubicin (Cerubidine, Rubidomycin), were used during treatment, a follow-up echocardiogram (ECG or EKG) may be recommended every 5 years. Although the risk to any one individual is small, radiation therapy increases the risk of secondary brain tumors, as well as the risk of learning disabilities. Patients should receive follow-up screening at gradually increasing intervals to monitor for:
Note that much of the data used to demonstrate that childhood cancer survivors are good candidates for insurance will come through the collection of long-term, follow-up data on survivors. The child’s family is encouraged to organize and keep a record of the child’s medical information, so that as the child enters adulthood, he or she has a clear, written history of the diagnosis and details of the treatment given. The doctor’s office can help you compile this, and it should include recommendations from the doctor about the schedule for follow-up care. This information will be valuable to doctors who care for your child during his or her lifetime. Children who have had cancer can also enhance the quality of their future by following established guidelines for good health into and through adulthood, including not smoking, maintaining a healthy weight, eating a balanced diet, and participating in regular physical activity. Talk with the doctor about developing a plan that is best for your child’s needs. Find out more about common terms used after cancer treatment is complete. Current Research
Research for childhood ALL is ongoing. The following advances may still be under investigation in clinical trials and may not be approved or available at this time. Always discuss all diagnostic and treatment options with your doctor. Monitoring leukemia recurrence. New methods for detecting small numbers of leukemic cells, too small to see under a microscope, were introduced in the 1990s. These techniques are now being used to detect minimal residual disease (MRD) following remission. There are times when measurements of MRD, in blood or bone marrow samples, will be used to determine your child’s risk level and treatment. Research is ongoing to determine the level of MRD, measured at which time point, that affects the rate of recurrence and whether changes in treatment will impact the meaning of these measurements and their affect on the cure. Current investigations are studying the relationship between the biology of the leukemic cells and these measurements. New treatments. Finding new ways to treat leukemia are important areas of research. New drugs to kill leukemia cells, such as the T-cell-specific drug nelarabine (Arranon), and the antibody epratuzumab (LymphoCide) are under investigation and may improve the cure rate for children with ALL in the future. Other new agents—antibodies, chemotherapy, and other biologically active agents—are being explored with the hope that they will increase the cure rate and/or decrease the likelihood of side effects. Questions to Ask the Doctor
Regular communication with your child’s doctor is important in making informed decisions about your child’s health care. Consider asking the following questions of your child’s 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. |
