The treatment information in this document is not official policy of the Society and is not intended as medical advice to replace the expertise and judgment of your cancer care team. It is intended to help you and your family make informed decisions, together with your doctor.

Your doctor may have reasons for suggesting a treatment plan different from these general treatment options. Don't hesitate to ask him or her questions about your treatment options.

In recent years, much progress has been made in treating NHL. The treatment options depend on the kind of lymphoma, its stage, and the factors mentioned in the section "After the Tests: Staging." Of course, no two people are exactly alike, and treatments are often tailored to each person. It is often a good idea to get a second opinion. This can give you more information and help you feel more confident about the treatment plan you choose.

Many different types of treatment can be used to treat non-Hodgkin lymphoma.

Surgery

While surgery may be done to get a tissue sample in order to classify the lymphoma, it is not often used to treat NHL. It has been used to treat lymphomas that start in organs such as the stomach or thyroid, but only if it has not spread beyond these organs. If the lymphoma is only in one place, radiation treatment is more common than surgery.

Radiation Therapy

Radiation therapy is treatment with high energy rays (such as x-rays) to kill or shrink cancer cells. Radiation given from a source outside the body (external beam radiation) is the kind most often used to treat NHL. It might be used as the main treatment for early stage lymphomas, but more often it is used along with chemotherapy.

Radiation can also be used to ease symptoms involving organs such as the brain and spinal cord or to decrease pain when tumors are pressing on nerves.

Possible Side Effects

Side effects of radiation may include mild skin problems or fatigue. Radiation to the abdomen may cause upset stomach and diarrhea. Often these go away after a short while.

Long-term side effects are a bigger problem. Chest radiation may cause lung damage and lead to trouble breathing. Though not common, lung cancer can occur after lung radiation, especially among smokers. Side effects of brain radiation usually become most serious 1 or 2 years after treatment. They can include headaches and trouble with thinking. Other cancers can occur in places that received radiation. Although a person's risk of this happening is not high, this is a major problem because so many people with lymphoma are cured. Radiation may also make the side effects of chemotherapy worse.

Chemotherapy

Chemotherapy (often called "chemo") refers to the use of drugs to kill cancer cells. Usually the drugs are given into a vein or by mouth (as pills). They can also be injected into the spinal fluid to treat lymphoma cells on the surface of the brain or spinal cord. Once the drugs enter the bloodstream, they spread through the body, making this treatment very useful for lymphoma. Chemotherapy may be used alone or along with radiation treatment.

Often many chemotherapy drugs are combined. There are different treatment schedules. Treatments may be given several times in cycles 3 or 4 weeks apart. Most treatments are given in the doctor’s office (or clinic) on an outpatient basis, but some must be given in the hospital. A patient may take one combination of drugs for many cycles and later be switched to a different combination if the first one doesn’t seem to be working.

Possible Side Effects

While the drugs kill cancer cells, they also damage normal cells, causing side effects. The exact side effects depend on the type and dose of drugs used and the length of time they are taken. Side effects can include the following:

• hair loss 
• mouth sores 
• loss of appetite 
• nausea and vomiting 
• greater chance of infection (due to low white blood cell counts) 
• easy bruising or bleeding (from low platelet counts) 
• fatigue (due to low red blood cell counts)

Most of these side effects are short term and go away after treatment is finished. There are often ways to lessen these side effects. For example, there are drugs to help prevent or reduce nausea and vomiting.

Because many of the side effects of chemo are due to low white blood cell counts, some patients find it helpful to keep track of their counts. If you are interested in doing this, ask your doctor or nurse about your blood cell counts and what these numbers mean.

If your white blood cell counts are very low, you can lower your chances of infection by doing the following:

• Wash your hands often. 
• Avoid fresh, uncooked fruits and vegetables and other foods that might carry germs.
• Avoid fresh flowers and plants because they may carry mold. 
• Make sure other people wash their hands before they come in contact with you. 
• Avoid large crowds and people who are sick (wearing a surgical mask offers some protection).

Drugs known as growth factors are sometimes given to keep the white blood cell counts higher and reduce the chance of infection. Another way to prevent infection is to use powerful antibiotics early in the treatment process. If serious side effects occur, chemo may have to be reduced or stopped, at least for a short time.

Tumor lysis syndrome is caused by the rapid breakdown of cancer cells during chemo. When the cells die, they break apart and release their contents into the bloodstream. This “cell waste” can affect the kidneys, heart, and nervous system. To prevent this problem, extra fluids and certain drugs may be given to the patient.

Chemo can also cause side effects that can last over time or that might not happen until years after treatment. One of these is damage to bone marrow cells that can result in leukemia. Also, some drugs can damage heart muscle or cause damage to the kidneys or nerves.

Biological Therapy

This type of treatment uses natural substances made by the immune system to kill lymphoma cells or slow their growth. It is sometimes called immunotherapy.

Monoclonal Antibodies

These are like the antibodies made by the immune system to help fight infections, but they are made in the lab. Instead of attacking germs, they can be designed to attack lymphoma cells. Many monoclonal antibodies are now approved as treatments for lymphoma. The first one approved by the FDA to treat any cancer was rituximab (Rituxan). Patients receive these treatments (as infusions) over a period of about 4 weeks. The treatments can be given in the doctor’s office or clinic. Common side effects are usually mild and might include chills, fever, nausea, rashes, tiredness, and headaches. Newer forms of monoclonal antibodies have radioactive substances attached to them. Other monoclonal antibodies are also being developed.

Interferon

Interferons is a protein made by white blood cells to help fight infections. Some studies suggest that giving man-made interferon can cause some types of NHL to shrink. Side effects from this treatment can include tiredness, fever, chills, headaches, muscle and joint aches, and mood changes. Because of these side effects, interferon is not used very often.

High-Dose Chemotherapy and Bone Marrow or Peripheral Blood Stem Cell Transplant

Stem cell transplants are sometimes used to treat lymphoma patients who are in remission or who have a relapse during or after treatment.

Standard doses of chemo drugs can cause serious side effects to quickly dividing tissues such as the bone marrow. Even though higher doses of these drugs might work better to treat NHL, they are not given because the severe damage to bone marrow cells would cause lethal shortages of blood cells, and other vital organs would likely be damaged too.

A stem cell transplant (SCT) allows doctors to use higher doses of chemo and sometimes radiation therapy. After treatment is finished, the patient receives a transplant of blood-forming stem cells to restore the bone marrow.

Types of Transplants

There are 2 main types of stem cell transplants. The difference is the source of the blood-forming stem cells.

Autologous stem cell transplant: For this type of transplant, blood-forming stem cells from the patient’s own blood (or, less often, from the bone marrow) are removed, frozen, and stored. Then very high doses of chemotherapy (with or without radiation therapy) are given in order to kill the cancer. These high doses destroy bone marrow, too. When that happens, the body is no longer able to make new blood cells. So, after the treatment, the stored stem cells are thawed and given back to the patient through a vein. The cells enter the bloodstream and return to the bone, replacing the marrow and making new blood cells.

With some types of lymphoma that tend to spread to the bone marrow or blood, this type of transplant may not be possible because it may be hard to get stem cells free of cancer.

Allogenic stem cell transplant: In this approach, the stem cells come from someone else--usually a matched donor who tissue type is very close to the patient's. The donor may be a brother or sister or someone not related to the patient. Sometimes umbilical cord stem cells are used.

This type of transplant is not used a lot in treating NHL because it is often hard to find a matched donor. Another drawback is that the side effects of this treatment are often too severe for people over 55 years old.

The Transplant Process

The person getting the stem cell transplant may be admitted to the bone marrow transplant (BMT) unit of the hospital or receive treatment as an outpatient, depending on a number of factors.

The treatment works like this: stem cells are collected from the bloodstream in a process called apheresis. The cells are frozen and stored. Patients are then given very high doses of chemo to kill the cancer cells. The patient might also receive total body radiation to kill any remaining cancer cells. After treatment, the stored stem cells are given to the patient like a blood transfusion. The stem cells settle into the patient's bone marrow over the next several days and start to grow and make new blood cells.

People who receive a donor's stem cells are given drugs to prevent rejection. Usually within a couple of weeks after the stem cells are given, they start making new white blood cells. Then they begin making platelets, and finally, red blood cells.

Patients having SCT have to be kept away from germs as much as possible until their white blood cell count is at a safe level. They may be kept in the hospital or see the doctor every day until a measure of their white blood cells (the ANC) reaches a certain number, usually around 1,000. Even after the counts begin to return to normal, they will be seen as an outpatient regularly for about 6 months.

Some Things to Keep in Mind

Stem cell transplantation is a complex treatment. If the doctors think that a patient might be helped by this treatment, it is important that it be done at a hospital where the staff has experience with the procedure. Some transplant programs may not have experience in certain transplants, especially those from unrelated donors.

Stem cell transplant is very expensive (more than $100,000) and often involves a long hospital stay. Because some insurance companies see it as an experimental treatment, they might not pay for it. It is important to find out what your insurance will cover and what you might have to pay before deciding on a transplant.

Possible Side Effects

Side effects from stem cell transplant can be divided into short- and long-term effects. The short-term side effects are about the same as those caused by any other type of high-dose chemo. These side effects can include low blood cell counts (with increased risks of infection and bleeding), nausea, vomiting, loss of appetite, mouth sores, and hair loss.

Some side effects can last for a long time, or may not happen until years after the transplant. These long-term side effects can include the following:

• graft-versus-host disease (GVHD), which occurs only in a donor (allogeneic) transplant (see below) 

• infertility and early menopause in women 

• infertility in men 

• damage to the thyroid gland that causes problems with changing food into energy 

• cataracts (damage to the eye that can affect vision) 

• damage to the lungs, causing shortness of breath 

• bone damage (if damage is severe, the patient will need to have part of the bone and joint replaced) 

• getting leukemia several years later

Graft-versus-host disease is the main problem of a donor (allogeneic) stem cell transplant. It happens when the immune system of the patient is taken over by that of the donor. The donor immune system then starts to attack the patient’s other tissues and organs.

Symptoms can include severe skin rashes with itching and severe diarrhea. The liver and lungs may also be damaged. The patient may also become tired and have aching muscles. If severe enough, the disease can be fatal. Drugs that weaken the immune system may be given to try to control it. On the plus side, this disease also causes any remaining lymphoma cells to be killed by the donor immune system. Mild graft-versus-host disease can be a good thing.

"Mini Transplant"

Most patients over the age of 55 can't have a regular transplant that uses high doses of chemo. Some may be able to have what is called a "mini-transplant" (also called a non-myeloablative transplant or reduced-intensity transplant), where they get lower doses of chemo and radiation which do not destroy all the cells in their bone marrow. They then are given the donor stem cells. These cells enter the body and form a new immune system, which sees the cancer cells as foreign and attacks them (a "graft-versus-lymphoma" effect).

To learn more about stem cell transplants, see the American Cancer Society document, Bone Marrow & Peripheral Blood Stem Cell Transplants.