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Cancer Medicine :: Lymphoma - Non-Hodgkin - Childhood

Lymphoma - Non-Hodgkin - Childhood

General treatment information

Children and teens with lymphoma and their families have special needs. These needs can be met best by cancer centers for children and teens, working closely with the child’s primary care doctor. Treatment in these centers gives you the advantage of having teams of specialists who know the differences between cancers in adults and those in children and teens, as well as the unique needs of younger people with cancer.

For childhood lymphomas, this team is typically led by a pediatric oncologist, a doctor who uses chemotherapy and other medicines to treat children’s cancers. Many other specialists may be involved in your child’s care as well, including nurse practitioners, nurses, psychologists, social workers, rehabilitation specialists, and other health professionals.

After lymphoma is diagnosed and tests have been done to determine its stage, your child’s cancer care team will discuss the treatment options with you. The most important factors in choosing a treatment include the type and stage of the cancer, although other factors may also play a role.

Chemotherapy is the main treatment for all children with non-Hodgkin lymphoma, because it can reach all parts of the body and kill lymphoma cells wherever they may be. Even if the lymphoma appears to be limited to a single swollen lymph node, non-Hodgkin lymphoma in a child has often spread by the time it is diagnosed. Lymphoma cells are probably in other organs, but these are too small to be felt by the doctor or seen on imaging tests.

The intensive treatment for childhood lymphoma can possibly cause serious side effects. Before treatment starts, it’s a good idea to ask the pediatric cancer care team about the side effects your child might develop. They can tell you about common side effects, how long they might last, and how serious they might be.

Other types of treatment, such as surgery and radiation, play a much smaller role in treating childhood lymphoma. The next few sections describe the types of treatments used for non-Hodgkin lymphoma in children. This is followed by a description of the most common approaches used based on the type and stage (extent) of the lymphoma.

Surgery for non-Hodgkin lymphoma in children

Surgery often has a limited role in treating non-Hodgkin lymphoma since it’s unlikely to cure it by itself and normal organs might be damaged in the process. Surgery is sometimes used as the first treatment for early stage Burkitt lymphoma that is in only one area (such as part of the intestine) to try to remove as much of the tumor as possible before chemotherapy. If the lymphoma can be completely removed, doctors may be able to give a less intensive chemotherapy regimen.

Other uses of surgery include:

To get biopsy samples for lab tests to determine the exact type of non-Hodgkin lymphoma if non-surgical procedures (needle biopsy, bone marrow biopsy, etc.) could not get enough tissue.

To insert a small plastic tube, called a central venous catheter or venous access device (VAD), into a large blood vessel near the heart. The end of the tube stays just under the skin or sticks out in the chest area or upper arm. The VAD is left in place during treatment to give intravenous (IV) drugs such as chemotherapy and to take blood samples. This lowers the number of needle sticks needed during treatment.

To relieve some emergency situations, such as if a lymphoma has blocked a child’s intestines.

Possible risks and side effects of surgery

Possible complications of surgery depend on the location and extent of the operation and the child’s health beforehand. Serious complications, although rare, can include problems with anesthesia, excessive bleeding, wound infections, and pneumonia. Most children will have some pain for a while after the operation, although this can usually be helped with medicines if needed.

Radiation therapy for non-Hodgkin lymphoma in children

Radiation therapy uses high-energy rays to kill cancer cells. Radiation therapy was once a very common treatment for children with non-Hodgkin lymphoma. But as doctors have developed more effective chemotherapy treatments, the use of radiation therapy has become much more limited.

Radiation focused on a cancer from a source outside the body is called external beam radiation. This is the type of radiation therapy most often used to treat non-Hodgkin lymphoma. The treatment is much like getting an x-ray, but the radiation is more intense. Before the treatments start, the radiation team takes careful measurements to determine the correct angles for aiming the radiation beams and the proper dose of radiation. Each treatment lasts only a few minutes, although the setup time – getting your child into place for treatment – usually takes longer. The procedure itself is painless, but some younger children may need to be sedated to make sure they don't move during the treatment. Most often, radiation treatments are given 5 days a week for several weeks.

There are a few instances in which radiation therapy may be used.

Sometimes radiation is used along with chemotherapy, such as in patients where the lymphoma has reached the brain or spinal cord.

It may be used as a form of urgent treatment in children with symptoms caused by large tumors in the chest.

It may be used as part of treatment for children receiving a bone marrow or peripheral blood stem cell transplant .

It can also be used to relieve symptoms caused by lymphoma in internal organs, such when it is causing pain because it is pressing on nerves.

Possible risks and side effects of radiation therapy

Short-term side effects of radiation therapy may include sunburn-like skin problems or hair loss in the area being treated. Radiation therapy that includes large parts of the body can cause fatigue. Radiation of the abdomen may cause nausea, vomiting, or diarrhea. Often these effects go away after a short while.

Possible long-term side effects of radiation therapy in children can be more serious, and may occur after many years.

Chest radiation therapy may damage the lungs or heart, which could raise the risk of lung or heart problems later in life. In the long term, radiation to the chest may also increase the risk of lung cancer (especially in smokers) and of breast cancer.

Side effects of radiation therapy to the brain usually become most serious 1 or 2 years after treatment and may include headaches and problems such as memory loss, personality changes, and trouble learning at school.

Radiation to other parts of the body may slow their growth or increase the risks for certain other cancers, such as those of muscle or bone (called sarcomas) or of the digestive tract.

Because of these possible long-term effects, doctors try to avoid using radiation therapy in children or limit the doses used whenever possible.

Chemotherapy for non-Hodgkin lymphoma in children

Chemotherapy (chemo) uses anti-cancer drugs that are usually given into a vein or taken by mouth. These drugs enter the bloodstream and reach all areas of the body, making this treatment very useful for cancers that tend to spread widely, such as lymphomas. In some cases where the lymphoma may have reached the brain or spinal cord, chemotherapy may also be given into the cerebrospinal fluid.

The treatment for children with non-Hodgkin lymphoma is a combination of several chemo drugs given over a period of time. The number of drugs, their doses, and the length of treatment depend on the type and stage of the lymphoma. Some of the drugs commonly used to treat childhood lymphoma include:

Cyclophosphamide (Cytoxan)

Vincristine (Oncovin)

Doxorubicin (Adriamycin)

Prednisone

Cytarabine, also known as ara-C (Cytosar)

Methotrexate

L-asparaginase (Elspar), PEG-L-asparaginase (pegaspargase, Oncaspar)

Etoposide (VePesid, others)

6-mercaptopurine (Purinethol)

Ifosfamide (Ifex)

Doctors give chemo in cycles, in which a period of treatment is followed by a rest period to allow the body time to recover. Each chemo cycle generally lasts for several weeks. Most chemo treatments are given on an outpatient basis (in the doctor’s office or clinic or hospital outpatient department), but some – especially at the start of treatment – may need to be given while the child stays in the hospital.

Possible risks and side effects of chemotherapy

Chemo drugs attack cells that are dividing quickly, which is why they work against cancer cells. But other cells in the body, such as those in the bone marrow, the lining of the mouth and intestines, and the hair follicles, also divide quickly. These cells are also likely to be affected by chemotherapy, which can lead to side effects.

The side effects of chemo depend on the type and dose of drugs given and how long they are taken. These side effects can include:

Hair loss

Mouth sores

Loss of appetite

Nausea and vomiting

Diarrhea

Increased chance of infections (due to low white blood cell counts)

Easy bruising or bleeding (due to low blood platelet counts)

Fatigue (due to low red blood cell counts)

These side effects are usually short-term and go away after treatment is finished. If serious side effects occur, chemotherapy may have to be reduced or delayed. There are often ways to lessen these side effects. For example, there are drugs that can be given to help prevent or reduce nausea and vomiting.

Infections can be very serious in people getting chemo. Drugs known as growth factors can be given to keep the blood cell counts higher. Be sure to ask your child’s doctor or nurse about medicines to help reduce side effects, and let him or her know when your child does have side effects so they can be managed effectively.

Tumor lysis syndrome is a possible side effect of chemotherapy in children who had large numbers of lymphoma cells in the body before treatment. It occurs most often with the first cycle of chemo. When chemo kills these cells, they break open and release their contents into the bloodstream. This can overwhelm the kidneys, which aren’t able to get rid of all of these substances at once. Excess amounts of certain minerals may also affect the heart and nervous system. This problem can be prevented by making sure the child gets lots of fluids during treatment and by giving drugs such as bicarbonate, allopurinol, and rasburicase, which help the body get rid of these substances.

Some possible side effects occur only with certain drugs. For example, drugs such as doxorubicin can damage the heart. Your child’s doctor may order heart function tests (like a MUGA scan or echocardiogram) if your child is getting one of these drugs. Be sure to ask your child’s doctor or nurse about any specific side effects you should watch for and about what you can do to help reduce these side effects.

Along with the side effects listed above, there are possible long-term effects of chemotherapy in children, such as possible effects on fertility later in life.

Monoclonal antibodies for non-Hodgkin lymphoma in children

Antibodies are proteins normally made by the body’s immune system to help fight infections. Man-made versions, called monoclonal antibodies, can be designed to attack a specific target, such as a substance on the surface of lymphoma cells.

Several monoclonal antibodies are now being used to treat lymphoma in adults. Some of these are now being studied for use in children as well.

Rituximab (Rituxan) is an antibody that attaches to a substance called CD20 that is found on the surface of some types of lymphoma cells. This attachment seems to cause the lymphoma cell to die. Rituximab is being studied for use along with chemotherapy. The treatments are given as intravenous (IV) infusions in the doctor’s office or clinic. Common side effects are usually mild but may include chills, fever, nausea, rashes, fatigue, and headaches during or after the infusion. Even if these symptoms occur with the first rituximab infusion, it is unusual for them to recur with later doses. Rituximab may also increase a person’s risk of infections.

Other monoclonal antibodies, such as ibritumomab (Zevalin) and tositumomab (Bexxar), are similar to rituximab but have radioactive molecules attached to them. The antibodies bring radiation directly to the lymphoma cells, which may help them work better. These drugs are somewhat harder for doctors to give because of the radiation dosing involved. They are sometimes used to treat adults with certain lymphomas, but their usefulness in children is just beginning to be studied.

Brentuximab vedotin (Adcetris) is an anti-CD30 antibody attached to a chemotherapy drug. Some lymphoma cells have the CD30 molecule on their surface. The antibody acts like a homing signal, bringing the chemo drug to the lymphoma cells, where it enters the cells and causes them to die when they try to divide into new cells. Brentuximab can be used to treat anaplastic large cell lymphoma (ALCL) that has come back after other treatments. So far it has been used mainly in adults, but it is now being studied in children as well. It is given as an infusion into a vein (IV) every 3 weeks. Common side effects include nerve damage (neuropathy), low blood counts, fatigue, fever, nausea and vomiting, infections, diarrhea, and cough.

High-dose chemotherapy and stem cell transplant for non-Hodgkin lymphoma in children

A stem cell transplant allows doctors to use higher doses of chemotherapy than the body would normally tolerate. Stem cell transplants are not used as the first treatment for non-Hodgkin lymphoma in children, but a transplant may be an option if the first treatment does not work or if the lymphoma comes back after treatment.

Giving higher doses of chemotherapy might be more likely to kill all of the lymphoma cells, but doctors can’t do it routinely because it destroys the bone marrow, which is where new blood cells are formed. This could lead to life-threatening infections, bleeding, and other serious problems because of low blood cell counts. A stem cell transplant lets doctors use higher doses of chemotherapy and, sometimes, radiation therapy. After the chemotherapy is finished, the child receives a transplant of blood-forming stem cells to restore the bone marrow. These stem cells can either be taken from the child before treatment (autologous stem cell transplant) or donated from another person (allogeneic stem cell transplant).

Autologous stem cell transplant

In an autologous bone marrow transplant (BMT) or peripheral blood stem cell (PBSC) transplant, blood-forming stem cells are removed from your child’s bone marrow or blood on several occasions in the weeks before treatment. The stem cells are carefully frozen and stored.

Your child then receives high doses of chemotherapy and sometimes radiation treatment to destroy the lymphoma cells, which also destroys the cells in the bone marrow. The frozen stem cells are then thawed and returned to the child as a blood transfusion after the treatment.

For childhood non-Hodgkin lymphoma, this type of transplant is done more often than an allogeneic transplant (unless the lymphoma has already reached the bone marrow).

Allogeneic stem cell transplant

In an allogeneic stem cell transplant, the stem cells come from someone else. This type of transplant may be used if lymphoma cells are found in a child’s own bone marrow in order to avoid returning cancer cells to the child after treatment.

The donor’s tissue type (also known as the HLA type) needs to match the patient’s tissue type as closely as possible to help prevent the risk of major problems with the transplant. Usually this donor is a brother or sister if they have the same tissue type as the patient. If a parent is a close match to the child, the parent’s cells can sometimes be used. If there are no relatives with a good match, the cells may come from an HLA-matched, unrelated donor – a stranger who has volunteered to donate their cells – if one can be found.

The stem cells for an allogeneic stem cell transplant are usually collected from a donor's bone marrow or peripheral (circulating) blood on several occasions. In some cases, the source of the stem cells may be blood collected from an umbilical cord attached to the placenta after a baby is born (which is rich in stem cells). Regardless of the source, the stem cells are then frozen and stored until they are needed for the transplant.

How stem cells are transplanted

The child will typically be admitted to the stem cell transplant unit of the hospital on the day before the high-dose chemo begins. He or she will usually stay in the hospital until after the chemo and the stem cells have been given, and until the stem cells have started making new blood cells again (see below).

The child receives high-dose chemotherapy and sometimes radiation treatment. This destroys any remaining cancer cells, as well as the normal cells in the bone marrow. After treatment, the frozen stem cells are thawed and given as a blood transfusion. The stem cells then travel to the child’s bone marrow, where they will start to grow and make new blood cells.

Usually within a couple of weeks after the stem cells have been infused, they begin making new white blood cells. This is later followed by new platelet production and new red blood cell production. In the meantime, the child is at high risk for serious infections because of a low white blood cell count, as well as bleeding because of a low platelet count. During this time, blood and platelet transfusions and treatment with IV antibiotics are often used to help prevent or treat infections or bleeding problems.

Because of the high risk of serious infections right after treatment, patients usually stay in a special hospital room in protective isolation (guarding against exposure to germs) until part of their white blood cell count (known as the absolute neutrophil count, or ANC) rises above 500. They may be able to leave the hospital when their ANC is near 1,000.

The child is then seen in an outpatient clinic almost every day for several weeks. Because platelet counts often take longer to return to a safe level, the child may get platelet transfusions as an outpatient. Patients may make regular visits to the outpatient clinic for about 6 months, after which time their care may be continued by their regular doctors.

Practical points

A stem cell transplant procedure is a complex treatment that can cause life-threatening side effects. If the doctors think your child may benefit from a transplant, the best place to have this done is at a nationally recognized cancer center where the staff has experience with the procedure and with managing the recovery period.

Stem cell transplants often require a long hospital stay and can be very expensive. Be sure to get a written approval from your insurer if it is recommended for your child. Even if the transplant is covered by your insurance, co-pays or other costs could easily amount to tens of thousands of dollars. Find out what your insurer will cover before the transplant so you will have an idea of what you might have to pay.

Possible side effects

The possible side effects from SCT are generally divided into early and long-term effects.

Early or short-term side effects

The early complications and side effects are basically the same as those caused by high-dose chemotherapy (see the “Chemotherapy” section of this document), and can be severe. They are caused by damage to the bone marrow and other quickly growing tissues of the body, and can include:

Low blood cell counts (with fatigue and increased risks of infection and bleeding)

Nausea and vomiting

Loss of appetite

Mouth sores

Diarrhea

Hair loss

One of the most common and serious short-term effects is the increased risk of serious infections. Antibiotics are often given to try to prevent this. Other side effects, like low red blood cell and platelet counts, may require blood product transfusions or other treatments.

Long-term side effects

Some complications and side effects can persist for a long time or may not occur until years after the transplant. These can include:

Graft-versus-host disease (GVHD), which can occur in allogeneic (donor) transplants. This happens when the donor’s immune system cells attack tissues of the patient’s skin, liver, and digestive tract. Symptoms can include severe skin rashes, diarrhea, weakness, fatigue, mouth sores, nausea, yellowing of the skin and eyes (jaundice), and muscle aches. GVHD can also cause lung damage, leading to problems breathing. In severe cases, GVHD can be life-threatening. GVHD is often described as either acute or chronic, based on how soon after the transplant it begins. Drugs that weaken the immune system are often given to try to keep GVHD under control, although they can have their own side effects.

Radiation damage to the heart or lungs

Problems with the thyroid or other hormone-making glands

Problems with fertility

Damage to bones or problems with bone growth

Development of another cancer (including leukemia) years later

Be sure to talk to your child’s doctor before the transplant to learn about possible long-term effects your child may have. 

Complementary and alternative therapies for non-Hodgkin lymphoma in children

When your child has lymphoma you are likely to hear about ways to treat cancer or relieve symptoms that your doctor hasn’t mentioned. Everyone from friends and family to Internet groups and Web sites may offer ideas for what might help. These methods can include vitamins, herbs, and special diets, or other methods such as acupuncture or massage, to name a few.

What exactly are complementary and alternative therapies?

Not everyone uses these terms the same way, and they are used to refer to many different methods, so it can be confusing. We use complementary to refer to treatments that are used along with your regular medical care.Alternative treatments are used instead of a doctor’s medical treatment.

Complementary methods: Most complementary treatment methods are not offered as cures for cancer. Mainly, they are used to help people feel better. Some methods that are used along with regular treatment are: art therapy or play therapy to reduce stress; acupuncture to help relieve pain; or peppermint tea to relieve nausea. Some complementary methods are known to help, while others have not been tested. Some have been proven not to be helpful, and a few have even been found harmful.

Alternative treatments: Alternative treatments may be offered as cancer cures. These treatments have not been proven safe and effective in clinical trials. Some of these methods may pose danger, or have life-threatening side effects. But the biggest danger in most cases is that your child may lose the chance to be helped by standard medical treatment. Delays or interruptions in medical treatments may give the cancer more time to grow and make it less likely that treatment will help.

What happens during and after treatment for non-Hodgkin lymphoma in children?

During and after treatment for lymphoma, the main concerns for most families are the immediate and long-term effects of the lymphoma and its treatment, and concerns about possible recurrence of the cancer.

It is certainly normal to want to put the lymphoma and its treatment behind you and to get back to a life that doesn’t revolve around the cancer. But it’s important to realize that follow-up care is a central part of this process that offers your child the best chance for recovery and long-term survival.

Follow-up exams

It is very important for your child to have regular follow-up exams with the cancer care team for several years after treatment. The doctors will continue to watch for possible signs of lymphoma, as well as for short-term and long-term side effects of treatment. Doctor visits will be more frequent at first, but the time between visits may be extended as time goes on.

Checkups after treatment of non-Hodgkin lymphoma typically include careful physical exams, lab tests, and sometimes imaging tests such as CT scans. If the lymphoma recurs (comes back), it is usually while the child is still getting treatment or just after. It is unusual for childhood lymphoma to return if there are no signs of the disease within a year after treatment.

A benefit of follow-up care is that it gives you a chance to discuss questions and concerns that arise during and after your child's recovery. For example, almost any cancer treatment can have side effects. Some may last for a few weeks to several months, but others can be permanent. It is important to report any new symptoms to the doctor right away so that the cause can be found and treated, if needed.

It is also important to keep medical insurance. Even though no one wants to think of the cancer coming back, it is a possibility. If it happens, the last thing you want is to have to worry about paying for treatment.

Social, emotional, and other issues in treating non-Hodgkin lymphoma

Emotional issues may arise both during and after treatment. Factors such as the child’s age at diagnosis and the extent of treatment may play a role here.

During treatment, families tend to focus on the daily aspects of getting through it and beating the lymphoma. Some common family concerns include financial stresses, transportation to the cancer center, the possible loss of a job, and the need for home schooling. Many experts recommend that school-aged patients attend school as much as possible. This helps them maintain important social connections and gives them a chance to keep their friends informed about what is happening.

Friends can be a great source of support, but patients and parents should know that some people have misunderstandings and fears about cancer. Some cancer centers have a school re-entry program that can help in these situations. In this program, health educators visit the school and tell students about the diagnosis, treatment, and changes that the cancer patient may go through. They also answer any questions from teachers and classmates.

Centers that treat many children with lymphoma may have programs to introduce new patients to children or teens who have finished their treatment. This can give patients and their families an idea of what to expect during and after treatment, which is very important. Seeing another patient with lymphoma doing well after treatment is often helpful. Support groups also might be helpful.

During and after treatment, a number of emotional concerns may arise. Some of these may last a long time. They can include things like:

Dealing with physical changes that result from the treatment

Worries about the lymphoma returning or new health problems developing

Feelings of resentment for having had lymphoma or having to go through treatment when others do not

Concerns about being treated differently or discriminated against (by friends, classmates, coworkers, employers,etc.)

Concerns about dating, marrying, and having a family later in life

No one would choose to have lymphoma, but for many childhood lymphoma survivors, the experience can eventually be positive, helping to establish strong self-values. Other survivors may have a harder time recovering, adjusting to life after cancer, and moving on. It is normal to have some anxiety or other emotional reactions after treatment, but feeling overly worried, depressed, or angry can affect many aspects of a young person’s growth. It can get in the way of relationships, school, work, and other aspects of life.

With support from family, friends, other survivors, mental health professionals, and others, many people who have survived cancer can thrive in spite of the challenges they’ve had to face. If needed, doctors and other members of the health care team can often recommend special support programs and services to help children after cancer treatm.

Long-term effects of cancer treatment for non-Hodgkin lymphoma in children

Because of major advances in treatment, more children treated for lymphoma are living into adulthood. With childhood lymphoma survivors living longer, their health as they get older has come more into focus in recent years.

Just as the treatment of childhood lymphoma requires a very specialized approach, so does follow-up and monitoring for late effects of treatment. Careful follow-up after treatment is very important.

Childhood lymphoma survivors are at risk, to some degree, for several possible late effects of their cancer treatment. This risk depends on a number of factors, such as the type of lymphoma, the type of treatments they received, dosages of cancer treatment, and age at the time treatment.

Late effects of treatment can include:

Heart or lung problems after getting certain chemotherapy drugs or getting radiation therapy to the chest

Slowed or decreased growth and development (especially after a stem cell transplant)

Bone damage or thinning of bones (osteoporosis)

Changes in sexual development and ability to have children

Changes in intellectual function with learning difficulties

Development of second cancers, such as leukemia, later in life. These are not common, but they can occur.

There may be other possible complications from treatment as well. Your child’s doctor should carefully review any possible problems with you before your child starts treatment.

Along with physical side effects, survivors of childhood cancer may have emotional or psychological issues that need to be addressed. They also may have some problems with normal functioning and school work. These can often be addressed with support and encouragement. Doctors and other members of the health care team can also often recommend special support programs and services to help children after cancer treatment.

What`s new in research and treatment of non-Hodgkin lymphoma in children?

Research on the causes, diagnosis, and treatment of childhood non-Hodgkin lymphoma is being done at many medical centers, university hospitals, and other institutions across the nation.

Genetics

As noted in the section, “Do we know what causes non-Hodgkin lymphoma in children?” scientists are making great progress in understanding how changes in DNA can cause normal lymphocytes to develop into lymphoma cells.

Understanding the gene changes that often occur in non-Hodgkin lymphoma is providing insight into why these cells may grow too quickly, live too long, and do not develop into normal, mature cells. This information is being used to develop new treatments for lymphoma.

This progress has also led to vastly improved and highly sensitive tests for detecting and monitoring this disease. Tests such as the polymerase chain reaction (PCR) can identify non-Hodgkin lymphoma cells based on some of these gene changes. This test is useful in determining how completely the lymphoma has been destroyed by treatment and whether a relapse is likely if further treatment is not given.

Clinical trials of new treatments

Most children with non-Hodgkin lymphoma are treated at major medical centers, where treatment often involves taking part in clinical trials to provide the most up-to-date care. Several important questions are now being studied in clinical trials, such as:

Can all early stage (stages I and II) non-Hodgkin lymphomas be treated similarly?

What is the best length of treatment of each type of non-Hodgkin lymphoma?

Can less intense treatment provide as good an outcome as the highly intense treatments and thus help children possibly avoid some long-term side effects?

Can new chemotherapy drugs and new combinations of drugs improve cure rates?

Can newer, targeted drugs such as monoclonal antibodies be added to current treatments to make them better? 

An example of a promising new drug is crizotinib (Xalkori). This drug targets the anaplastic lymphoma kinase (ALK)gene, which is often abnormal in anaplastic large cell lymphoma (ALCL). In early studies, this drug has shown very promising results in children with ALCL that is no longer responding to other treatments. Doctors are now trying to determine how to best fit this drug into the treatment of ALCL.

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