Treatment

The treatment of NHL depends on the stage of the cancer, whether the cancer has spread, and the person’s overall health. In many cases, a team of doctors will work with the patient to determine the best treatment plan.

This section outlines treatments that are the standard of care (the best treatments available) for this specific type of cancer. Patients are also encouraged to consider clinical trials when making treatment plan decisions. A clinical trial is a research study to test a new treatment to prove it is safe, effective, and possibly better than standard treatment. Your doctor can help you review all treatment options. For more information, visit the Clinical Trials section.

There are three main treatments for NHL: chemotherapy, radiation therapy, and immunotherapy. Occasionally, surgery may play a role.

Watchful waiting

Some patients with indolent lymphoma may not require any immediate treatment if they are otherwise healthy and the lymphoma is not causing any symptoms or problems with other organs. In these cases, patients are closely monitored using physical examinations, CT and PET scans, and other laboratory tests on a regular basis. Treatment only begins if symptoms or tests indicate that the cancer is progressing. This approach is referred to as watchful waiting (also called watch-and-wait and active surveillance). There is very good evidence that, in some patients with indolent lymphoma, the watch-and-wait approach does not affect the chances of survival as long as regular and careful follow-up is performed.

Chemotherapy

Chemotherapy is the use of drugs to kill cancer cells and bone marrow. It is the primary treatment for NHL. Chemotherapy may be given by mouth or injected into a vein. Systemic chemotherapy is delivered through the bloodstream, targeting cancer cells throughout the body.

The chemotherapy used depends on the stage and type of the cancer. The most common chemotherapy combination for the initial treatment of NHL is called CHOP and contains four drugs: cyclophosphamide (Cytoxan, Neosar), doxorubicin (Adriamycin), vincristine (Oncovin), and prednisone (a type of corticosteroid). Recent evidence has shown that for most patients with B-cell lymphoma, the addition of rituximab (see the section on monoclonal antibodies below) to CHOP gives better results than the use of CHOP alone.

The side effects of chemotherapy depend on the individual, type of drug and dose used, and how long it is taken, but can include fatigue, risk of infection, nausea and vomiting, loss of appetite, and diarrhea. These side effects can be controlled during treatment and usually go away once treatment is finished. Chemotherapy may also cause long-term side effects, also called late effects.

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 high energy x-rays or other particles to kill cancer cells and shrink cancerous tumors. Radiation treatment for NHL is usually external-beam radiation therapy, which is radiation given from a machine outside the body. It is mainly used for patients who have a tumor in the early-stage disease or have a lymph node that is particularly large (usually more than 10 centimeters). Radiation therapy is usually given following or in addition to chemotherapy. It is often given to patients who have mediastinal B-cell lymphoma, which is more similar to a tumor.

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. Radiation therapy may also cause late effects.

Immunotherapy

Immunotherapy (also called biologic therapy) is designed to boost the body’s natural defenses to fight the cancer. It uses materials either made by the body or in a laboratory to bolster, target, or restore immune system function. Monoclonal antibodies, interferon, and vaccines are biologic therapies being tested in clinical trials as treatments for NHL.

Monoclonal antibodies. The monoclonal antibody, rituximab, is used to treat many different types of B-cell lymphoma. Rituximab works by targeting a molecule called CD20 that is located on the surface of lymphoma cells. When the antibody attaches to this antigen, some lymphoma cells die and others appear to become more susceptible to chemotherapy. Although it is quite effective by itself, there is increasing evidence that, when added to chemotherapy for patients with most types of B-cell NHL, it produces better results than chemotherapy alone.

Radiolabeled antibodies. Radiolabeled antibodies are monoclonal antibodies with radioactive particles attached that are designed to focus radioactivity directly on the lymphoma cells. This type of drug (ibritumomab [Zevalin] and tositumomab [Bexxar] and iodine I-131 are the drugs currently available) is relatively new and much is still being learned. In general, the radioactive antibodies are thought to be stronger than regular monoclonal antibodies but more damaging to the bone marrow. This type of therapy is referred to as radioimmunotherapy (RIT).

Interferon. Interferons are proteins that help strengthen the immune system and are given alone or together with chemotherapy for some types of low-grade lymphoma.

Stem cell transplantation/bone marrow transplantation

A stem cell transplant is a medical procedure in which diseased bone marrow is replaces by highly specialized cells, called hematopoietic stem cells. Today, this procedure is more commonly called a stem cell transplant, rather than a bone marrow transplant, because blood stem cells are typically what is being transplanted (injected into a vein), not the actual bone marrow. It is a difficult treatment and is generally reserved for patients with NHL whose disease is progressive or recurrent.

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

In 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 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; 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 both types, the goal of transplantation is to destroy cancer cells in the marrow, blood, and other parts of the body and have replacement blood stem cells create healthy bone marrow. In most stem cell transplants, the patient is treated with high doses of chemotherapy and/or radiation therapy to destroy as many cancer cells as possible. These high doses are used since patients who undergo this treatment have disease that has proven to be resistant to normal chemotherapy doses. Higher doses of chemotherapy are more effective against recurrent NHL than standard doses of chemotherapy. This chemotherapy and/or radiation therapy 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 or 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.) It is sometimes given to patients who may not have the strength to go through the standard bone marrow transplantation process and is being evaluated in clinical trials to determine if it is effective in treating lymphoma.

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 two 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 ALLO transplant, another major risk is that the donor’s cells will recognize the patient’s body as foreign, causing graft-versus-host disease (GVHD). GVHD may be a serious complication of allogeneic transplants and can be fatal. Other side effects may include liver problems, diarrhea, infections, and rashes. However, GVHD can also be a benefit, in that the donor cells can recognize the cancer cells as foreign and destroy these cells, a mechanism that is one of the major reasons why ALLO transplantation generally works so well over the long term. The risk of GVHD can be reduced with exact HLA-type matching and the use of preventative drugs.

In 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.

Refractory NHL and recurrent NHL treatment

If NHL is still present after initial treatment, the disease is called refractory NHL. As explained earlier, recurrent NHL is when the disease comes back after initial treatment. Choice of treatment for NHL in these settings depends on three factors: where the cancer is, the type of treatment given previously, and the patient’s overall health. The doctor may use chemotherapy or bone marrow transplantation or may recommend a clinical trial.

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