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Cancer Medicine :: Leukemia - Acute Lymphoblastic - ALL - Childhood Treatment

Leukemia - Acute Lymphoblastic - ALL - Childhood

Treatment Options

The following are used to describe the state of disease for children with ALL:

Untreated ALL. The child has not 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. However, it is very important to continue treatment, even when a child is in remission, to keep the leukemia from coming back.

Recurrent ALL. Recurrent ALL is leukemia 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, in other areas of the body. 

Refractory ALL. The leukemia did not go into remission, despite remission induction treatment .

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 proven 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 their health and 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. In many cases, a team of doctors works with a child and the family to provide care; this is called a multidisciplinary team. Pediatric cancer centers often have extra support services for children and their families, such as child life specialists, nutritionists, social workers, and counselors. Special activities and programs to help your child and family cope may also be available.

Descriptions of the most common treatment options for childhood ALL are listed below. 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. Treatment options and recommendations depend on several factors, including the classification of ALL, possible side effects, and the patient’s preferences and overall health. 

Chemotherapy

Chemotherapy is the use of drugs to kill cancer cells, usually by stopping the cancer cells’ ability to grow and divide. Systemic chemotherapy is delivered through the bloodstream to reach cancer cells throughout the body. Chemotherapy is given by a pediatric hematologist-oncologist; a doctor who specializes in treating cancer in children with medication. A chemotherapy regimen (schedule) usually consists of a specific number of cycles of drugs given over a set period of time. A patient may receive one drug at a time or combinations of different drugs at the same time.

Chemotherapy is the primary treatment for ALL. It may be given by mouth (orally), injected into a vein or muscle, or injected into the cerebral spinal fluid (CSF). It is generally done in four phases:

Remission induction therapy uses chemotherapy to kill as many of the leukemia cells as possible to cause the cancer to go into remission.

Central nervous system directed therapy kills any leukemia cells in the central nervous system and prevents the spread of the disease to the spinal fluid.

Consolidation therapy begins when the child’s leukemia has gone into remission. Higher doses of chemotherapy, or drugs not used during previous treatment, are used to kill the majority of the remaining leukemia cells.

Continuation or maintenance therapy lasts for two to three years to kill any remaining (residual) leukemia cells.

The side effects of chemotherapy depend on the individual and the dose used, but they can include short-term side effects like hair loss, fatigue, loss of appetite, nausea and vomiting, diarrhea, and kidney and liver dysfunction. If a drug called vincristine (Oncovin, Vincasar) is part of your child’s chemotherapy, there may be muscle weakness and nerve pain. These side effects usually go away once treatment is finished. Other side effects related to chemotherapy that may last longer or develop after treatment is finished include bone and joint problems and learning problems. 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 side effects each child experiences 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.

The medications used to treat cancer are continually being tested. 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. 

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. A radiation therapy regimen (schedule) usually consists of a specific number of treatments given over a set period of time.

Radiation therapy for ALL is generally used only when the leukemia 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 hair loss, 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 possibly include hormone problems affecting growth and metabolism, learning problems, and an increased risk of developing a second cancer including a brain tumor. Skin, salivary gland, and thyroid cancers can also occur after treatment for ALL . 

Stem cell transplantation/bone marrow transplantation

Stem cell transplantation is most often used as a treatment for recurrent or refractory ALL. Rarely, transplantation may be recommended as part of the initial therapy when leukemia is associated with very high risk features. 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 it is the blood stem cells that are typically being transplanted, not the actual bone marrow tissue.

Before recommending transplantation, doctors will talk with the patient and family members 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.

There are two types of stem cell transplantation depending on the source of the replacement blood stem cells: allogeneic (ALLO) and autologous (AUTO).

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. 

Palliative/supportive care

Leukemia and its treatment often cause side effects. In addition to treatment to slow, stop, or eliminate the disease, an important part of care is relieving a child’s symptoms and side effects. This approach is called palliative or supportive care, and it includes supporting the patient with his or her physical, emotional, and social needs.

Palliative care can help a child at any stage of illness. Children often receive treatment for the leukemia and treatment to ease side effects at the same time. In fact, patients who receive both often have less severe symptoms, better quality of life, and report they are more satisfied with treatment.

Before treatment begins, talk with your child’s health care team about the possible side effects of the specific treatment plan and supportive care options. And during and after treatment, be sure to tell your doctor or another health care team member if your child is experiencing a problem, so it is addressed as quickly as possible. 

Recurrent ALL

A remission is when leukemia cannot be detected in the body and there are no symptoms. This may also be called “no evidence of disease” or NED. 

A remission can be temporary or permanent. This uncertainty leads to many families feeling worried or anxious that the leukemia will come back. While many remissions are permanent, it’s important to talk with your child’s doctor about the possibility of the disease returning. Understanding the risk of recurrence and the treatment options may help you feel more prepared if the leukemia does return.

If the ALL recurs, a cycle of testing will begin again to learn as much as possible about the recurrence. After testing is done, you and your child’s doctor will talk about treatment options. Often the treatment plan will include the therapies described above (such as chemotherapy, radiation therapy, and/or stem cell transplantation) but may be used in a different combination or given at a different pace. Your child’s doctor may also suggest clinical trials that are studying new ways to treat this type of recurrent cancer. Just as for newly diagnosed patients, clinical trials typically offer the best chance of cure.

If the ALL recurs, treatment 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 leukemia cells are found in the bone marrow, CSF, testicles, or in more than one of these sites when it recurs.

When ALL recurs, patients and their families often experience emotions such as disbelief or fear. Families are encouraged to talk with their health care team about these feelings and ask about support services to help them cope. 

If treatment fails

Although treatment is successful for the majority of children with cancer, sometimes it is not. If a child’s leukemia cannot be cured or controlled, this is called advanced or terminal leukemia. This diagnosis is stressful, and it may be difficult to discuss. However, it is important to have open and honest conversations with your child’s doctor and health care team to express your family’s feelings, preferences, and concerns. The health care team is there to help, and many team members have special skills, experience, and knowledge to support patients and their families.

Parents or guardians are encouraged to think about where the child would be most comfortable: at home, in a home-like setting elsewhere, in the hospital, or in a hospice environment. Nursing care and special equipment can make staying at home a workable alternative for many families. Some children may be happier if they can arrange to attend school part-time or keep up other activities and social connections. The child’s health care team can help parents or guardians decide on an appropriate level of activity. Making sure a child is physically comfortable and free from pain is extremely important as part of end-of-life care. 

The death of a child is an enormous tragedy, and families may need support to help them cope with the loss. Pediatric cancer centers often have professional staff and support groups to help with the process of grieving.

Clinical Trials

Many clinical trials are focused on new treatments, evaluating whether a new treatment is safe, effective, and possibly better than the current (standard) treatment. These types of studies evaluate new drugs, different combinations of existing treatments, new approaches to radiation therapy or surgery, and new methods of treatment. Children who participate in clinical trials are often 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.

There are also clinical trials that study new ways to ease symptoms and side effects during treatment and manage the late effects that may occur after treatment. Talk with your doctor about clinical trials regarding side effects. In addition, there are ongoing studies about ways to prevent the disease

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 and their families 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 these studies are 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. 

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 that 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. 

Side Effects

Fear of treatment side effects is common after a diagnosis of leukemia, but it may help to know that preventing and controlling side effects is a major focus of your child’s health care team. This is called palliative or supportive care, and it is an important part of the overall treatment plan, regardless of the stage of disease.

Common side effects from each treatment option for ALL are described in detail within the Treatment section. Side effects depend on a variety of factors, including the classification, the length and dosage of treatment(s), and your child’s overall health.

Before treatment begins, talk with your child’s doctor about possible side effects of each type of treatment your child will be receiving. Ask which side effects are most likely to happen, when they are likely to occur, and what can be done to prevent or relieve them. And, ask about the level of caregiving your child may need during treatment and recovery, as family members and friends often play an important role in the care of a person with ALL. 

In addition to physical side effects, there may be psychosocial (emotional and social) effects as well. Patients and their families are encouraged to share their feelings with a member of their health care team who can help with coping strategies. 

During and after treatment, be sure to tell the health care team about the side effects your child experiences, even if you feel they are not serious. Sometimes, side effects can last beyond the treatment period, called a long-term side effect. A side effect that occurs months or years after treatment is called a late effect. Treatment of both types of effects is an important part of survivorship care. 

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 your child received, the doctor will determine what examinations and tests are needed to check for long-term side effects. The possible long-term side effects associated with specific treatments are listed in the table below:

Type of Treatment

Possible Late Effects

Chemotherapy with cyclophosphamide (Cytoxan, Neosar)  and/or etoposide (VePesid, Toposar)

Secondary cancers

Infertility (the inability to have children)

Chemotherapy with types of drugs called anthracyclines, such as doxorubicin (Adriamycin) or daunorubicin (Cerubidine)

Heart problems

Radiation therapy

Hormone problems affecting growth and metabolism

Secondary cancers

Infertility

Learning problems

High-dose chemotherapy or spinal fluid injections of chemotherapy like methotrexate (multiple brand names) and cytarabine (Cytosar-U)

Learning problems

Patients should receive follow-up screening at gradually increasing intervals to monitor for the possible side effects listed above, as well as liver disease from chemotherapy or transfusion-related infection (both very rare) and bone health. 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.

Survivors should be sensitive to their level of functioning and level of stress, and they may need counseling if they have any problems. It is important that children who have trouble with school have neuropsychological testing (testing of thinking skills by a psychologist) to find the cause. Based on the results, the psychologist can advise teachers about changes that can be made in the classroom or teaching plan to help the child learn. Survivors should also be evaluated for bone or joint pain that may result from bone cell death caused by cancer treatments that reduce blood flow in bone joints. 

Childhood cancer survivors should also be aware of problems with getting health insurance. 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. That way, as the child enters adulthood, he or she has a clear, written history of the diagnosis, the treatment given, and the doctor’s recommendations about the schedule for follow-up care. The doctor’s office can help you create this. 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.  

Latest Research

Doctors are working to learn more about ALL, how to best treat it, and how to provide the best care to people diagnosed with this disease. The following areas of research may include new options for patients through clinical trials. Always talk with your child’s doctor about the diagnostic and treatment options best for your child.

Monitoring leukemia recurrence. New methods for detecting small numbers of leukemia cells that can’t be seen under a microscope were introduced in the 1990s. These techniques are now being used to detect minimal residual disease (MRD) after 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. This research also looks at whether changes in treatment will change the meaning of MRD measurements and their effect on the cure. Currently, researchers are studying the relationship between the biology of the leukemia 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 being studied and may improve the cure rate for children with ALL in the future. Other new treatments—antibodies, chemotherapy, and other biologically active treatments—are being studied with the hope that they will increase the cure rate and/or decrease the likelihood of side effects.

Supportive care. Clinical trials are underway to find better ways of reducing symptoms and side effects of current childhood ALL treatments in order to improve patients’ comfort and quality of life.

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