Non-Hodgkin lymphoma (NHL) is a cancer of a type of white blood cell called lymphocytes. Lymphocytes are part of the immune system that protects the body from infection and disease. NHL is a group of 30 or more cancers that begin in the lymphocytes.
These cancers are similar in some ways but have many differences in the way they affect people. They are all called non-Hodgkin lymphoma to distinguish them from another cancer of the lymphocytes called Hodgkin lymphoma.
Non-Hodgkin lymphoma symptoms and diagnosis
NHL is the fifth most common cancer in the United States, with about 56,000 cases diagnosed each year. Although NHL can occur in people of any age, fewer than 5% of people with NHL are children. The risk of getting NHL increases with age, and the average age at diagnosis is about 65. It occurs somewhat more often in men than women. For most people, the cause of NHL is unknown.
Lymphocytes and symptoms of NHL
NHL is a cancer of the lymphocytes. Lymphocytes make antibodies, proteins that attach to foreign cells and mark them to be attacked. Lymphocytes also direct the rest of the immune system to attack the foreign cells and help in the attack.
Lymphocytes are stored in lymph nodes and travel through the body in a network of small lymph vessels. As fluid carrying the lymphocytes passes through the lymph nodes, the lymph nodes filter out bacteria and viruses that can cause infection. This is why the lymph nodes sometimes become swollen when the body is fighting an infection.
Infection is by far the most common cause of a swollen lymph node, but a swollen lymph node can also be a symptom of NHL. NHL begins when a lymphocyte changes into a cancer cell that divides and grows into more and more cancer cells. These cancer cells join, forming tumors (lymphomas) in the lymph nodes and elsewhere in the body.
Many people with NHL do not notice any symptoms. Their disease may be found during a routine physical exam or a test for another health problem. When people do notice symptoms, a swollen lymph node is the most common. Other symptoms may be caused by the growth of tumors. These symptoms depend on where the tumor is growing. For example, a person may have stomach pain or indigestion if a tumor grows in or near the stomach. Other common symptoms include:
- Night sweats
- Unexplained weight loss (losing more than 10% of the body's weight in six months)
- Fatigue or extreme tiredness
- Loss of appetite
- Very itchy skin
These symptoms can also be signs of other illnesses. If you have these symptoms, it is important to see your doctor for a diagnosis.
To diagnose lymphoma, a doctor will look at a sample of cells from an affected lymph node or tumor. Taking a sample of cells is called a biopsy. For a biopsy, a doctor usually removes all of the tumor in surgery, though sometimes only part of it is removed. The cell sample is checked in a laboratory to find out whether a person has lymphoma, the type of lymphoma and other information that can help a doctor plan treatment.
The doctor will also do a physical exam, health history and other tests to find out more about the lymphoma. These tests may include:
- Blood tests to:
- Count red blood cells, white blood cells and platelets — lymphoma can cause low numbers of one, two or all three types of blood cells.
- Look for changes in the blood that can be caused by disease in certain organs or tissues.
- Tests that can show if the lymphoma has spread, such as:
- Chest X-ray
- Computed tomography (CT or CAT) scan, which uses special X-rays to show cross-sections of the body's tissues and organs
- Magnetic resonance imaging (MRI), which uses magnets and radio waves to show detailed images of the body's tissues and organs
- Positron emission tomography (PET) scan, which shows an image of where lymphoma is active using a radioactive substance that is injected into a vein
- Tests on bone marrow samples to look for signs of disease in the marrow
- Lumbar puncture (spinal tap) to see if lymphoma has spread to the central nervous system
A doctor will diagnose the type of NHL, the stage (whether the tumor has spread and how far) and how fast the tumor is growing. The doctor will also assess a risk score. The risk score helps predict the chances that a person's disease will return after treatment as well as his or her overall chances of survival (prognosis). All of this information is important to planning the best treatment.
Non-Hodgkin lymphoma types, staging and risk scores
Types of NHL
Non-Hodgkin lymphoma includes more than 30 lymphomas that are different in many ways. These lymphomas can be grouped together based on how quickly they are growing:
- Lymphomas that tend to grow slowly are called indolent or low-grade lymphomas. Some — but not all — indolent lymphomas may need little treatment other than watchful waiting for years.
- Lymphomas that tend to grow quickly are called aggressive lymphomas. They may also be called intermediate-grade or high-grade. Aggressive lymphomas may become life-threatening within months without effective treatment.
Over time, an indolent lymphoma can sometimes change into an aggressive lymphoma.
Lymphomas are also grouped based on the type of lymphocyte that is affected. There are two kinds of lymphocytes that can develop lymphomas, B cells and T cells. Most NHLs (about 85%) are B-cell lymphomas.
Three of the more common types of NHL — all of which are sometimes treated with a bone marrow or cord blood transplant — are:
- Diffuse large B-cell lymphoma — About 30-35% of people with NHL have this type. It is an aggressive B-cell lymphoma.
- Follicular lymphoma — Worldwide about 20% of people with NHL have this type, but it is more frequent in North America. It is an indolent B-cell lymphoma.
- Mantle cell lymphoma — About 6% of people with NHL have this type. It is an aggressive B-cell lymphoma that is often widespread at diagnosis.
A doctor will also determine the stage of lymphoma, or how much cancer is in the body. The stage is based on how many groups of lymph nodes and/or organs show cancer and whether the cancer is limited to a small area or widespread. There are four stages. Stage I disease is limited to a small area, while stage IV disease is more widespread. The more widespread the disease, the harder it may be to treat the cancer.
When lymphomas are found early, they are more likely to be at stage I or II. Stages I and II are also called early-stage disease. However, it is more common to find lymphoma in a late stage. Lymphomas that have had more time to grow before they are discovered are likely to be at stage III or IV, also called late-stage disease.
Risk scores for NHL
When planning treatment, it can also be important to determine a patient's risk score. The risk score predicts the chances that a person's disease will return after treatment as well as his or her overall chances of survival. The risk score for NHL patients is based on a system called the International Prognostic Index (IPI). The IPI risk score is determined by factors including:
- Stage of the disease
- Performance status, or how well the person can do normal daily activities
- Number of areas or organs other than lymph nodes that show disease
- Amount of an enzyme called lactate dehydrogenase (LDH) in the blood — high levels of LDH may be a sign of fast-growing tumors
A person with a low IPI risk score has a low risk of disease returning after treatment. A person with a high IPI risk score has a high risk of disease returning after treatment. For someone with high-risk disease, a doctor may recommend more aggressive treatment or newer treatments being studied in clinical trials.
Planning non-Hodgkin lymphoma treatments
There are several treatment options for people with non-Hodgkin lymphoma. The most effective treatment for two people with NHL may be very different. If you have NHL, your doctor will plan your treatment based on your specific situation. The best treatment for you depends on the type and stage of NHL you have, your risk score, your own choices and other factors specific to you.
Watch and wait
For some people with indolent lymphoma who have few or no symptoms, a doctor may recommend a plan of watchful waiting. To watch and wait means not treating the disease right away. Instead, regular doctor visits are used to watch for changes in disease.
For some people, the disease may change very little for a long time. With watchful waiting, they can avoid the possible risks and side effects of other treatment during this time. If the disease becomes more active, treatment can begin.
For patients whose lymphoma is active, the main treatment options (all discussed further below) include:
- Radiation therapy
- Bone marrow or cord blood transplant (also called a BMT)
These treatments may be used alone or used in combination. For some people with relapsed follicular or diffuse large B-cell lymphoma or with mantle cell lymphoma, a transplant may offer the best chance of long-term remission. A transplant is a strong treatment with risks of serious side effects, so it is not used for all patients with NHL. A transplant is used when other treatment options are unlikely to provide a long-term remission.
Whichever treatment you and your doctor decide on, you may choose to be part of a clinical trial. Even standard treatments continue to be studied in clinical trials. These studies help doctors improve treatments so that more patients can have better results.
Chemotherapy for non-Hodgkin lymphoma
Chemotherapy has been used as a treatment for NHL for many years. Chemotherapy uses drugs to destroy cancer cells or stop them from growing. The goal is to either slow down the disease or to bring it into remission (no more signs of disease). There are many different chemotherapy drugs and combinations of drugs that may be used to treat NHL. Chemotherapy may also be used in combination with other treatments for NHL.
Chemotherapy for indolent lymphoma
For indolent lymphomas, chemotherapy often brings a remission, but relapse (return of the disease) is common. At relapse, a doctor may recommend repeated chemotherapy or another treatment option, such as a transplant or immunotherapy. For some people, repeated relapses can be managed with chemotherapy for many years and they may have a good quality of life much of the time.
However, less than half of patients with indolent lymphoma have a long-term remission with chemotherapy alone. Over time, the disease may develop into an aggressive form of lymphoma. If this happens, a bone marrow or cord blood transplant may be a treatment option.
Chemotherapy for aggressive lymphomas
Aggressive lymphomas are usually treated with a combination of chemotherapy drugs. It is also common to combine the chemotherapy with a type of immunotherapy called monoclonal antibody therapy.
If there is disease in the central nervous system or risk that disease will spread there, the patient may receive additional chemotherapy injected directly into the fluid around the spinal cord. This is called intrathecal chemotherapy.
Chemotherapy can often bring aggressive lymphomas into remission. Long-term remissions are more common for aggressive lymphoma than for indolent lymphoma. However, for patients with a high IPI risk score, there is a high risk of relapse. Further treatment is usually recommended while the disease is still in remission. Common treatments at this point are more chemotherapy or a bone marrow or cord blood transplant.
Radiation therapy for NHL
Radiation therapy uses energy to stop cancer cells from growing and multiplying. Radiation therapy is often part of the treatment for NHL, especially for disease in an early stage, when the lymphoma is limited to a small area. If the lymphoma is indolent and in an early stage, radiation therapy may be used alone. Often, however, radiation therapy is used together with chemotherapy.
For patients with NHL, radiation may be directed at the area including the neck, chest and lymph nodes under the arms. This area is called the mantle field. Radiation may also be given to a larger area (extended field) or only to the part of the body where cancer was found and to nearby lymph nodes. The area treated and dose given depend on the patient's specific diagnosis. Radiation may also be targeted to cancer cells using a type of immunotherapy called monoclonal antibodies, as described below.
Immunotherapy for NHL
Immunotherapy (also called biological therapy) is treatment that uses parts of the immune system to fight disease. There are several different types of immunotherapy that may be used to treat NHL. Immunotherapy is a newer approach, and many immunotherapy treatments are offered through clinical trials.
Monoclonal antibody therapy
The most common immunotherapy for NHL is rituximab. Rituximab is a monoclonal antibody therapy. An antibody is a protein the immune system uses to mark foreign cells (such as infection) to be attacked by other immune cells. Monoclonal antibodies are made in a laboratory and designed to mark specific types of cells. Rituximab and other monoclonal antibodies used to treat B-cell lymphomas are designed to mark the B lymphocytes for attack by the body's immune system.
Today, essentially all patients with B-cell lymphomas will receive monoclonal antibody therapy, usually in combination with chemotherapy. Newer monoclonal antibody therapies may be available in clinical trials or are in development in the laboratory.
Monoclonal antibodies with radiation — radioimmunotherapy
Another type of immunotherapy that may be used to treat NHL is called radioimmunotherapy. Radioimmunotherapy uses monoclonal antibodies to carry radiation directly to cancer cells. When the antibodies attach to a cancer cell, the cell receives a dose of direct radiation.
Radioimmunotherapy has been used to treat some types of B-cell lymphoma when the disease has relapsed or does not respond to other treatment. Radioimmunotherapy is being studied in clinical trials as a first treatment option, sometimes in combination with chemotherapy. Radioimmunotherapy is also being studied as part of the treatment to prepare a patient for a transplant using his or her own blood-forming cells (autologous transplant).
Another type of immunotherapy that may be used to treat lymphoma is interferon therapy. Interferons are proteins that the body produces to help fight infection or cancer. The type of interferon used to treat NHL is called interferon-alpha (INFa).
Some studies have shown interferon-alpha can shrink lymphomas and lengthen remission in some people with follicular lymphoma, indolent T-cell lymphoma or hairy cell lymphoma. In other studies, interferon has been less effective. Interferon-alpha is being studied in clinical trials to find the best uses for this therapy, including using it together with chemotherapy or with other forms of immunotherapy.
Other forms of immunotherapy
Other immunotherapy treatments for NHL are being studied in clinical trials. Your doctor can recommend whether any clinical trials of newer immunotherapy treatments may be an option for you.
Bone marrow or cord blood transplant for NHL
For some patients, a bone marrow or cord blood transplant (also called a BMT) may offer the best chance for a long-term remission. A transplant destroys cancer cells with high-dose chemotherapy and sometimes radiation therapy and/or uses immune cells from a donor to attack the cancer cells.
There are two types of transplant that may be used to treat someone with NHL. An autologous transplant uses blood-forming cells collected from the patient. An allogeneic transplant uses blood-forming cells from a family member or unrelated donor or cord blood unit.
A transplant can offer some people with NHL the chance for a long-term remission of disease, but it has serious risks and is not an option for all patients. A transplant may be an option for people with certain types of NHL who:
- Are younger. In general, younger patients tend to do better after a transplant than older patients. However, treatment advances have enabled more older patients to undergo a transplant successfully.
- Are in good overall health, other than their NHL. People with other health problems may be unable to tolerate a transplant.
- Have a suitable donor or cord blood unit, if an allogeneic transplant is an option.
A consultation with a transplant doctor can help a patient determine whether a transplant is a good option, either as a first treatment or as a backup plan. The National Marrow Donor Program® (NMDP)* and the American Society for Blood and Marrow Transplantation (ASBMT) recommend a patient be referred to a transplant doctor for consultation if he or she has:
- Follicular lymphoma and:
- Does not have a good response to his or her first treatment
- Stays in a first remission less than 12 months before having a relapse
- Relapses a second time
- The lymphoma develops into diffuse large B-cell lymphoma
- Diffuse large B-cell lymphoma and:
- Relapses one or more times
- Is in first complete remission and has a high or high-intermediate IPI risk score
- Does not reach a complete remission after the first treatment
- Mantle cell lymphoma, after first treatment
*The NMDP, which operates Be The Match®, also conducts research to learn how to improve patient outcomes.
For an autologous transplant, blood-forming cells are collected from the patient's blood stream or bone marrow. The cells are usually collected after the disease has been brought into remission. The patient is treated with high-dose chemotherapy and sometimes radiation therapy and/or immunotherapy to destroy cancer cells.
This treatment also destroys blood-forming cells, so the patient receives his or her own cells back to replace cells that were destroyed. The high-dose treatment is more intense than can be given without a transplant, so it may be able to destroy more cancer cells.
An allogeneic transplant provides the patient with healthy blood-forming cells from a family member or unrelated donor or cord blood unit. The cancer cells are destroyed by the transplant preparative regimen of high-dose chemotherapy and sometimes radiation therapy and/or by the immune cells received from the donor.
An allogeneic transplant has a higher risk of serious side effects than an autologous transplant. However, the risk of relapse is lower after an allogeneic transplant. One reason for a lower relapse rate may be that the donor's immune cells attack the cancer cells to prevent a relapse. This is called the graft versus lymphoma effect. The graft is the donated cells received in the transplant.
In many studies comparing autologous transplants to allogeneic transplants for NHL, overall survival rates are similar or higher after autologous transplant than after allogeneic. The choice between an autologous and an allogeneic transplant may depend on a patient's type of NHL and risk score. If you have NHL, a transplant doctor can recommend whether either an autologous or an allogeneic transplant is a good treatment option for you.
Choosing a donor or cord blood unit for allogeneic transplant
If an allogeneic transplant may be an option for you, you will need a donor. Your doctor will test your blood to find out your HLA tissue type. Your doctor will also test possible donors in your family to find out if they are a suitable match for you. If you do not have a suitable donor in your family, your doctor can work with the NMDP to search for an unrelated donor or cord blood unit from our Be The Match Registry® and other registries worldwide. To save time, your doctor may check for potential donors on the registry at the same time he or she is testing for donors in your family.
The closeness of the donor match can affect a patient's chances of a good transplant outcome. In general, a closely matched sibling donor can give a better chance of survival than an unrelated donor. However, because of advances in unrelated donor transplant in the last decade, for some groups of patients, outcomes for sibling donor and unrelated donor transplants are similar.
Reduced-intensity allogeneic transplants
People who are older or have other health problems, such as heart disease or organ damage from previous chemotherapy, may be unable to tolerate the usual high-dose preparative regimen for an allogeneic transplant. However, a transplant using less intense treatment may be an option for some of these patients. This type of transplant is called a reduced-intensity transplant or non-myeloablative transplant.
A reduced-intensity transplant uses lower doses of chemotherapy and low-dose or no radiation therapy. It relies on the donor's immune cells to attack cancer cells (the graft versus lymphoma effect). This approach may reduce some of the early complications of allogeneic transplants. As a treatment for NHL, reduced-intensity transplant has been used mostly for patients who have relapsed after an autologous transplant or other previous treatment.
Transplant success rates
Transplants have risks of serious complications, but a transplant offers some patients the best chance for a long-term remission. If transplant is an option for you, your doctor can talk with you about the possible risks and benefits of a transplant. For statistics showing patients' results after transplant, see NHL Transplant Outcomes.
Making treatment decisions
If you are diagnosed with NHL, it is important to talk with a doctor who has experience treating NHL. There are many types of NHL, and the course of the disease can be very different for different people. There are also a variety of treatment options available, including newer treatments available in clinical trials. It is important to talk with your doctor about your disease, risk score and treatment options as well as your own treatment goals. The best treatment for you will depend on your NHL type, stage and risk score, age and overall health, as well as your own preferences.
Planning for a possible transplant
If a transplant may be a treatment option for you, your doctor will refer you to a transplant doctor for a consultation. A transplant doctor can determine whether a transplant is a good treatment option for you. A transplant doctor can also help determine whether an autologous or allogeneic transplant is a better option and the best time for a transplant.
For some people, a transplant soon after a first remission is a good choice. For others, a good choice may be to wait and see whether the disease relapses before deciding to have a transplant. An early consultation with a transplant doctor enables your doctors to plan ahead even if a transplant is not your first treatment choice.
If an autologous transplant is planned, you will need to have your blood-forming cells collected and stored. If an allogeneic transplant is an option, the transplant doctor can begin the search for a suitable donor among family members and the Be The Match Registry of unrelated donors and cord blood units.
Information to share with your doctor
The Physician Resources section of this Web site includes information for doctors about timing and outcomes of transplants for NHL, as well as references to related medical journal articles. You may want to share some of this information with your doctor.
More information about NHL
You can get further information about NHL from disease-specific organizations, such as:
For other organizations that offer information and resources, see Organizations That Can Help: A Searchable Directory.
James O. Armitage, M.D., University of Nebraska Medical Center, Omaha, Neb.
C. F. LeMaistre, M.D., Southwest Texas Methodist Hospital, San Antonio, Texas
Paul Shaughnessy, M.D., Texas Transplant Institute, San Antonio, Texas