Treatment

Clinical trials are the standard of care for the treatment of children with cancer. In fact, more than 60% of children with cancer are treated as part of a clinical trial. Clinical trials are research studies that compare the standard treatments (best treatments available) with newer treatments that may be more effective. Cancer in children is rare, so it can be hard for doctors to plan treatments unless they know what has been most effective in other children. 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. 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. An increasing number of pediatric cancer centers also have services for teenagers and young adults. Sometimes, adult cancer centers participate in the same studies for these teens and young adults.

Treatment of Hodgkin lymphoma consists of chemotherapy and/or radiation therapy. There is no role for surgery as a treatment approach, except in some cases of localized lymphocyte predominant Hodgkin disease (LPHD).

The amount and type of treatment used to treat Hodgkin lymphoma depends on how many lymph node areas are involved and how large the nodes have grown. Children with more widespread (advanced) or "bulky" disease may have more rounds of chemotherapy and radiation therapy than children with early stage disease. New studies of childhood Hodgkin lymphoma are trying to further reduce the amount of treatment to avoid long-term side effects.

Chemotherapy

Chemotherapy is the use of drugs to kill cancer cells. Systemic chemotherapy uses drugs to target cancer cells throughout the body.

For children and adolescents, chemotherapy is virtually always used. Classic treatments for Hodgkin lymphoma were a combination of chemotherapy called ABVD (doxorubicin [Adriamycin], bleomycin [Blenoxane], vinblastine [Velban], dacarbazine [DTIC]) or MOPP (mechlorethamine [Mustargen], vincristine [Oncovin], prednisone, procarbazine [Matulane]). These combinations are no longer the standard of care for children because others with less long-term side effects are available. Newer treatments for children use many of these agents, but replace nitrogen mustard with cyclophosphamide [Cytoxan, Neosar] and often replace procarbazine with etoposide [VePesid] to limit the risk of infertility (the inability to have children). More recently, treatments plans for later stage disease have been designed to improve effectiveness by using more dose-density therapies (such as the combinations called ABVE-PC, Stanford V, and BEACOPP), often given for shorter periods of time.

Because chemotherapy attacks rapidly dividing cells, including those in normal tissues such as the hair, lining of the mouth, intestines, and bone marrow, children receiving chemotherapy may lose their hair, develop mouth sores, or have nausea and vomiting. In addition, chemotherapy may lower the body's resistance to infection, lead to increased bruising and bleeding, and cause fatigue. These side effects can be controlled during treatment and usually go away after chemotherapy is completed. 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 long-term side effects of chemotherapy also depend on the type and total dose of each drug. Higher doses of chemotherapy can affect heart and lung function and cause infertility in the future. Rarely, children with Hodgkin lymphoma develop a second cancer, acute myeloid leukemia, because of chemotherapy's effects on bone marrow function. Fortunately, the risk of long-term side effects is much lower with newer treatment plans that limit the doses of drugs that cause serious health problems. The pediatric clinical trials now in use in most treatment centers use much less amounts of the drug that may affect the heart (doxorubicin) than the dosages used in many treatment plans for adults (particularly for advanced stage disease). The drugs being tested are also unlikely to cause infertility (for instance, procarbazine is no longer used in these clinical trials). Current pediatric clinical trials also evaluate reduced doses of drugs effective for lymphoma but could cause leukemia in the long-term.

Doctors may recommend treatment with chemotherapy alone or a combination of chemotherapy and radiation therapy for children with Hodgkin lymphoma. For later stage disease, current trials often include radiation therapy. For earlier stage disease, many research studies do not include radiation therapy for those who will benefit from chemotherapy.

For children with bulky and advanced disease, many doctors feel that the combination treatment gives the best chance for cure because there are two ways to attack the cancer cells. In combination treatment, doctors reduce the total amount of chemotherapy and radiation therapy, which should reduce health problems after treatment. The most important consideration is to use sufficient therapy to cure the disease with the first treatment plan, because the intensity of therapy for recurrent disease is high.

The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications prescribed for you, their purpose, and their potential side effects or interactions with other medications. Learn more about your prescriptions through Cancer.Net's Drug Information Resources, which provides links to searchable drug databases.

Radiation therapy

Radiation therapy is the use of x-rays or other particles to kill cancer cells. The most common type of radiation treatment is called external-beam radiation therapy, which is radiation therapy given from a machine outside the body. Treatments for Hodgkin lymphoma in the past used high doses of radiation therapy to all of the lymph node areas. Children treated this way had problems with the growth of muscles and bones and had a higher risk of second cancers as they got older.

Today, treatment with radiation therapy alone is rarely used in children. Doctors combine chemotherapy with low-dose radiation treatment given to areas where lymph nodes contain cancer.

Radiation therapy remains a primary treatment for Hodgkin lymphoma. Pediatric approaches use lower dose (20-25 Gy) and reduced volume (involved field or involved node) compared with traditional regimens. The need for radiation therapy is determined by both stage of disease and its response to chemotherapy. Clinical trials are currently in progress to identify the patients that are most likely to benefit from chemotherapy so they may not need radiation therapy.

Full-dose radiation (30-45 Gy) therapy, necessary to cure Hodgkin disease if chemotherapy is not used, has been associated with significant potential for hypoplasia (limited growth of bone and muscle) in growing children and second cancers (especially breast cancer) as well as thyroid, heart, reproductive, and lung problems.

Short-term side effects from radiation therapy include tiredness, sore throat, dry mouth, mild skin reactions, upset stomach, and loose bowel movements.

Long-term side effects of radiation therapy may include growth problems of bones and soft tissues; thyroid, heart, and lung problems; and second cancers. The risk of long-term side effects is much lower with newer radiation therapy techniques that deliver low doses only to cancerous lymph nodes while protecting normal tissues. While the risk of breast cancer increases after high-dose radiation therapy in girls treated around the time of puberty, the risk of lower doses is less clear. Since early atherosclerotic heart disease, another significant, long-term risk of radiation therapy, affects boys as well, the current approach is to limit radiation therapy for both boys and girls, if possible. However, radiation therapy is a very effective treatment for Hodgkin lymphoma and plays a major role in achieving a cure.

Recurrent Hodgkin lymphoma

Recurrent Hodgkin lymphoma is disease that comes back after treatment. The disease can come back in the same area it began or in a new area of the body. Treatment for recurrent Hodgkin lymphoma depends on where the disease recurs, the type of treatment the child has had previously, and the time since the first treatment was completed. For example, if radiation therapy was the original treatment, then chemotherapy may be used as a second treatment. If chemotherapy was given initially, then the child may be given another round of chemotherapy using different drugs. Ifosfamide (Ifex) and vinorelbine (Navelbine) have recently been shown to be an effective treatment for recurrent disease in children and adolescents, and are now the standard drugs recommended prior to stem cell transplantation/bone marrow transplantation (see below) in the Children's Oncology Group studies. The combination of gemcitabine (Gemzar) with vinorelbine also has recently been shown to be quite effective in children and adolescents.

If the disease has come back very soon after the first treatment or after the use of both chemotherapy and radiation therapy, more aggressive therapy including a stem cell transplantation may be recommended to increase the chances of keeping the disease in remission (the disappearance of the signs and symptoms of the disease).

Stem cell transplantation/bone marrow transplant

Often when high doses of chemotherapy or radiation therapy are used to treat recurrent Hodgkin lymphoma, the bone marrow becomes damaged and can't produce healthy blood cells. To replace those lost cells, a hematopoietic stem cell transplant (SCT) may be recommended.

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 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, called HLA-typing. Most often, a patient's brother or sister serves as the donor, although unrelated donors can serve as the donor too. Millions of people worldwide have volunteered to donate stem cells for patients who do not have matched family members; matches can be made by searching a computer registry. In addition, 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 the high-dose treatment for the transplant is completed.

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 "minitransplants" or "reduced intensity transplants" have less immediate side effects, allowing the procedure to be used for more older patients.

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 two to three weeks. Because there are considerable risks with transplantation, the doctor will consider several factors, including the patient's age and general health, before recommending this approach. 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 is a serious complication of allogeneic transplants and can be fatal. Other side effects may include liver problems, diarrhea, infections, and rashes. At the same time, the donor cells can also recognize the cancer cells as foreign and destroy these cells, a mechanism that is one of the major reasons why ALLO transplantation generally works well over the long term.

However, ALLO transplants have not been used as frequently in patients with recurrent Hodgkin lymphoma because of the greater risks of serious side effects. A study in the Children's Oncology Group is trying to achieve the benefits of ALLO transplantation without the risks by using drugs (cyclosporine [Neoral], interferon gamma [Actimmune], and interleukin-2 [Proleukin]) that may cause the immune system to attack the tumor cells.

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 by reading the Cancer.Net Feature series, Understanding Bone Marrow and Stem Cell Transplantation.

To learn about the terms used in this section, read the Cancer.Net Feature: Cancer Terms to Know: During Treatment.