- How is non-Hodgkin lymphoma treated?
- Chemotherapy for non-Hodgkin lymphoma
- Radiation therapy for non-Hodgkin lymphoma
- Immunotherapy for non-Hodgkin lymphoma
- High-dose chemotherapy and stem cell transplant for non-Hodgkin lymphoma
- Surgery for non-Hodgkin lymphoma
- Clinical trials for non-Hodgkin lymphoma
- Complementary and alternative therapies for non-Hodgkin lymphoma
- Treating specific types of non-Hodgkin lymphoma
- Palliative care for non-Hodgkin lymphoma
- More treatment information for non-Hodgkin lymphoma
Treating specific types of non-Hodgkin lymphoma
Diffuse large B-cell lymphoma
In most cases, the treatment for diffuse large B-cell lymphoma (DLBCL) is chemotherapy (chemo), usually with a regimen of 4 drugs known as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), plus the monoclonal antibody rituximab (Rituxan). This regimen, known as R-CHOP, is usually given for about 6 months.
If the lymphoma is stage I or II (that is, if it is localized to 1 or 2 lymph node groups on the same side of the diaphragm), radiation therapy to the lymph node areas may be added to treatment with R-CHOP. If radiation is given, then the treatment time with R-CHOP may be shortened to about 2 to 3 months. Sometimes, if the lymphoma mass is large, radiation may be added after a full course of treatment (about 6 months) with R-CHOP.
For stage III or IV lymphomas, most doctors will give R-CHOP for about 6 months as first-line treatment, although some doctors may prefer to give other chemo regimens. People with lymphoma in certain locations (such as the sinuses or testicles) are often given chemo to treat the brain and spinal cord as well.
Some studies have suggested that for younger patients with a high International Prognostic Index (IPI) score, high-dose chemo followed by an autologous stem cell transplant may be better than chemo alone. But it’s not yet clear if transplants are better as the initial treatment. Most doctors feel that if a transplant is done as part of the first treatment, it should be done in a clinical trial.
If the lymphoma doesn’t go away completely with treatment or if it recurs (comes back) after treatment, doctors will usually suggest another chemo regimen. Several different regimens are being used, and they may or may not include rituximab. If the lymphoma shrinks with this treatment, a stem cell transplant is often suggested if possible, as it offers the best chance of curing the lymphoma. Stem cell transplants are not effective unless the lymphoma responds to chemo. Unfortunately, not everyone is a good candidate for a stem cell transplant. Clinical trials of new treatments may be another good option for some people.
DLBCL can be cured in about half of all patients, but the stage of the disease and the IPI score can have a large effect on this. Patients with lower disease stages have better survival rates, as do patients with lower IPI scores.
Primary mediastinal B-cell lymphoma: This lymphoma is treated like a localized diffuse large B-cell lymphoma. The main treatment is usually about 6 courses of CHOP chemo plus rituximab (R-CHOP). A PET/CT scan is typically done after the chemo to see if there’s any tumor remaining in the chest. If no active lymphoma is seen on the PET/CT, the patient may be observed without further treatment. If the PET/CT scan is positive (shows possible active lymphoma), radiation may be needed. Often, the doctor will order a biopsy of the chest tumor to confirm that lymphoma is still present before starting radiation.
This type of lymphoma is often slow growing and responds well to treatment, but it is very hard to cure. It is common for this lymphoma to come back after treatment, although it can take years to do so. It is not always clear if treating the lymphoma right away is helpful. Because of this, some doctors recommend no treatment until the lymphoma has begun to cause problems other than mildly swollen lymph nodes. Some patients may never need treatment at all. In those that do, treatment is needed after an average of about 3 years.
If treatment is needed and the lymphoma is localized to 1 lymph node group or to 2 nearby groups on the same side of the diaphragm (stage I or early stage II), it can often be treated with only radiation therapy to the lymph node areas.
Regardless of the stage of the lymphoma, there are usually several treatment options. Many doctors will first try rituximab (Rituxan) combined with chemo, using either a single chemo drug (such as bendamustine or fludarabine) or a combination of drugs, such as the CHOP or CVP regimens. Rituximab alone or chemo alone (either one or several drugs) may also be used. Large areas of follicular lymphoma may also be treated with radiation to reduce symptoms, even if it’s not stage I or II.
The radioactive monoclonal antibody tositumomab (Bexxar) is also a possible treatment option, although it is more often used as a second-line treatment than in newly-diagnosed patients. It is usually given alone, but in some cases chemo may be given too.
For patients who may not be able to tolerate more intensive chemo regimens, rituximab alone, milder chemo drugs (such as chlorambucil or cyclophosphamide), or both may be good options.
If the lymphoma shrinks or goes away with the initial treatment, doctors may advise either close follow-up or further treatment. This might include either rituximab for up to 2 years or treatment with a radioactive antibody. Further treatment may lower the chance that the lymphoma will come back later and may help some patients live longer, but it can also have side effects.
If follicular lymphoma doesn’t go away after initial treatment or if it comes back later, other treatment approaches such as using different chemo drugs, monoclonal antibodies, or some combination of these can be tried. If the lymphoma responds to this treatment, a stem cell transplant may be an option.
In some cases, follicular lymphoma can change (transform) into or return as a diffuse large B-cell lymphoma. When this happens, the treatment is the same as for this more aggressive disease.
Chronic lymphocytic leukemia/small lymphocytic lymphoma
Like follicular lymphoma, these types of lymphoma are often slow growing, but they are very hard to cure. The treatment of chronic lymphocytic leukemia (CLL) is described in detail our document Leukemia -- Chronic Lymphocytic.
Treatment for both CLL and small lymphocytic lymphoma (SLL) is generally similar to that for follicular lymphoma. When the lymphoma is only in one lymph node or lymph node area (Ann Arbor stage I), it may be treated with radiation treatment alone. Often, disease that isn’t causing any problems or growing quickly can be watched closely without treatment for a time. When treatment is needed, chemo, with or without rituximab, is the usual first-line treatment. Treatment depends on the age and health of the patient, as well as on whether the cancer cells have certain chromosome changes.
Other monoclonal antibodies are most often used as second-line treatment if the disease doesn’t respond or comes back after initial treatment.
Mantle cell lymphoma
This type of lymphoma is very hard to cure. It has often spread widely when it’s first found, and although it doesn’t usually grow as quickly as some fast-growing lymphomas, it often doesn’t respond as well to treatment, either. Because current treatments for this type of lymphoma are very unlikely to cure it, patients might want to consider taking part in a clinical trial.
Early stage lymphomas (stages I or II), which are extremely rare, can sometimes be treated with radiation therapy. Otherwise, chemo plus rituximab is the usual treatment. When possible, the chemo treatment is intense, using combinations of drugs that may be changed during treatment. Less intense chemo regimens may be used for people who are older or who have other health issues. No specific regimen is clearly better than others, although there are reports that higher doses of chemo may be more effective. For those whose lymphoma responds well to initial treatment, a stem cell transplant may be a good option.
For mantle cell lymphomas that don’t respond or that come back after initial treatment, chemo with drugs such as fludarabine, cladribine, or pentostatin may be used, sometimes along with other chemo drugs or with rituximab. Newer drugs such as bortezomib (Velcade) and lenalidomide (Revlimid) and ibrutinib (Imbruvica) may also be options. The exact role of these drugs in treating mantle cell lymphoma is still being worked out in clinical trials.
Extranodal marginal zone B-cell lymphoma – mucosa-associated lymphoid tissue (MALT) lymphoma
The most common type, gastric (stomach) lymphoma, is thought to occur as a result of a chronic infection with the bacterium, H. pylori. Because of this, treatment for gastric lymphomas is different from treatment for the other lymphomas in this group.
For early-stage gastric MALT lymphomas (stages I and II) in people who test positive for H. pylori, treatment often consists of antibiotics, along with proton pump inhibitors, which are drugs that block acid secretion by the stomach. Usually the drugs are given for 10 to 14 days. This may be repeated after a couple of weeks. Examination of the stomach lining using gastroscopy (where a flexible tube with a viewing lens is passed down the throat) is then repeated at certain intervals to see if the H. pylori is gone and if the lymphoma has decreased in size. About 2 out of 3 of these lymphomas go away completely with antibiotic treatment, but it can sometimes take several months to be effective. In cases where symptoms need to be relieved before the antibiotics take effect or where antibiotics don’t shrink the lymphoma, radiation therapy to the area is often the preferred treatment. The monoclonal antibody rituximab may be another option.
For early stage gastric MALT lymphomas (stages I and II) in people who test negative for H. pylori, treatment is usually either radiation therapy to the stomach or rituximab.
For more advanced (stage III or IV) gastric MALT lymphomas, which are rare, treatment is often similar to that for follicular lymphoma (see above). Lymphomas that are not growing quickly may be followed without treatment right away. If the lymphoma is large, is causing symptoms, or is growing, radiation therapy to the stomach or chemo may be used. The drugs used are the same as those used for follicular lymphoma, and may include single agents such as chlorambucil or fludarabine or combinations such as CVP, often along with rituximab.
For MALT lymphomas that start in sites other than the stomach (non-gastric lymphomas), treatment depends on the site of the lymphoma and how extensive it is. Early stage lymphomas can often be treated with local radiation. In certain sites (such as the lungs, breast, or thyroid), surgery may be an option. For more advanced disease (stage III or IV), treatment is generally the same as for follicular lymphoma (see above).
Nodal marginal zone B-cell lymphoma
This rare type of lymphoma is generally slow growing. It is usually treated like follicular lymphoma (see above) with either close follow-up or low-intensity chemo. It can also change into a fast-growing large cell lymphoma, which would require more aggressive chemotherapy.
Splenic marginal zone B-cell lymphoma
This is also a slow-growing lymphoma. If it is not causing symptoms, it is often watched closely without treating it right away. If the spleen is enlarged, doctors may decide to remove it with surgery, especially if the patient has symptoms. This alone can sometimes lead to a long-term remission of the disease. Treatment with rituximab may be another option. Patients who have chronic hepatitis C virus infection may also benefit from treatment with anti-viral drugs.
If the disease is more advanced or progresses, it’s usually treated in the same way as a follicular lymphoma, which might include chemo or other options.
In some cases this lymphoma can transform into an aggressive large-cell lymphoma, which requires more intensive chemo.
This is a very fast-growing lymphoma that usually must be treated in the hospital with intensive chemo. Most regimens for this disease include at least 5 chemo drugs. Many regimens also include a steroid drug such as prednisone or dexamethasone. Rituximab may also be added. Because this lymphoma tends to invade the spinal fluid, a chemo drug such as methotrexate is given into the spinal fluid (this is called intrathecal therapy). Some examples of chemo regimens used for this lymphoma include hyper-CVAD, CODOX-M, and EPOCH.
An important part of the initial treatment of this disease is making sure these patients get plenty of fluids and drugs like allopurinol to help prevent tumor lysis syndrome (described in the “Chemotherapy for non-Hodgkin lymphoma” section).
More than half of all patients with Burkitt lymphoma can be cured with modern treatments.
Lymphoplasmacytic lymphoma (Waldenstrom macroglobulinemia)
The main treatment for this lymphoma is usually chemo or rituximab. For more detailed information see our document Waldenstrom Macroglobulinemia.
Hairy cell leukemia
This is a slow-growing lymphoma that tends to invade the spleen and lymph nodes as well as the blood. Patients without symptoms often don’t need to be treated right away, but they do need to have careful follow-up exams. These are done every few months to check for disease progression and the appearance of symptoms. Some patients with hairy cell leukemia (HCL) live for many years without having any symptoms or treatment.
Treatment may be advised for HCL patients with low blood cell counts, recurrent infections, or an enlarged spleen or lymph nodes. Treatment is most often with chemo drugs such as cladribine (2-CdA) or pentostatin. Up to 80% to 90% of patients respond to these drugs, and the responses last more than 5 years in most patients. Even if HCL recurs (comes back), many patients will respond to a second treatment with these drugs.
Giving rituximab after these drugs may get rid of any remaining disease in people who haven’t fully responded. Because this is a fairly rare disease, too few people have been treated with rituximab to know if it makes a difference.
In rare cases, HCL may not respond to chemo. Rituximab or interferon-alfa, a type of immunotherapy, may be helpful. If a patient is uncomfortable because of an enlarged spleen, removing the spleen by surgery (splenectomy) can often help relieve pain or other symptoms.
Precursor T-lymphoblastic lymphoma/leukemia
This disease can occur in both children and adults. The treatment for the lymphoma form of this disease is similar to that used for the leukemia form, which is discussed in more detail in our documents, Leukemia--Acute Lymphocytic (Adults) and Childhood Leukemia.
It’s considered a lymphoma if there are tumor masses and if lymphoma cells make up less than 25% of the bone marrow. This is a fast-growing disease that’s treated with intensive chemo when possible.
Combinations of many drugs are used. These can include cyclophosphamide, doxorubicin (Adriamycin), vincristine, L-asparaginase, methotrexate, prednisone, and, sometimes, cytarabine (ara-C). Because of the risk of spread to the brain and spinal cord, a chemo drug such as methotrexate is also given into the spinal fluid. Some doctors suggest maintenance chemo for up to 2 years after the initial treatment to reduce the risk of recurrence. High-dose chemo followed by a stem cell transplant may be another option.
An important part of the initial treatment of this disease is making sure patients get plenty of fluids and drugs like allopurinol, as they are at risk for tumor lysis syndrome (described in the “Chemotherapy for non-Hodgkin lymphoma” section).
Although this lymphoma is fast-growing, if it hasn’t spread to the bone marrow when it’s first diagnosed, the chance of cure with chemo is quite good. But once it has spread to the bone marrow, only about 40% to 50% of patients can be cured.
Cutaneous T-cell lymphomas (mycosis fungoides, Sezary syndrome, and others)
Treatment of these skin lymphomas is discussed in our document Lymphoma of the Skin.
Angioimmunoblastic T-cell lymphoma
This fast-growing lymphoma is often first treated with steroids (such as prednisone or dexamethasone) alone. This treatment can reduce fever and weight loss, but the effect is often temporary, and usually chemo is needed. Several chemo drugs are often used. If the lymphoma is only in one area, radiation therapy may be used as well.
Chemo rarely produces long-term remissions, so a stem cell transplant is often suggested after initial chemotherapy if a person can tolerate it.
Extranodal natural killer/T-cell lymphoma, nasal type
This rare lymphoma is often confined to the nasal passages. If there are no poor risk factors, radiation therapy alone may be an option. Otherwise, this lymphoma is usually treated with radiation therapy plus chemo, using a regimen such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). Chemo may be given into the spinal fluid as well.
If the lymphoma has spread or is outside the nasal passages, the chemo regimen may be more intense. Several drugs are used at high doses, and a stem cell transplant may be done if possible.
Enteropathy type T-cell lymphoma
This lymphoma develops from hypersensitivity to gluten, and is almost always in the intestines. It’s very hard to treat. Chemo using several drugs is usually the first treatment. If the lymphoma is only in one area, radiation therapy may be used as well. A stem cell transplant may be an option if the lymphoma responds to chemo.
Anaplastic large cell lymphoma
This lymphoma often responds well to treatment, and long-term survival is common, especially if the lymphoma cells stain positive for the ALK protein. If the cells lack the ALK protein or if the lymphoma returns after initial treatment, an autologous stem cell transplant may be an option. Another option for lymphomas that no longer respond to initial treatment is the labeled monoclonal antibody brentuximab vedotin (Adcetris).
Peripheral T-cell lymphoma, unspecified
These lymphomas are generally treated the same way as diffuse large B-cell lymphomas. Chemo with CHOP or other drug combinations is used. For early-stage disease, radiation therapy may be added. Stem cell transplants may be recommended as part of the treatment when possible.
If other treatments are no longer working, newer chemo drugs such as pralatrexate (Folotyn), targeted drugs such as bortezomib (Velcade), belinostat (Beleodaq), or romidepsin (Istodax), or immunotherapy drugs such as alemtuzumab (Campath) and denileukin diftitox (Ontak) may be tried.
The outlook is usually not as good as in diffuse B-cell lymphoma, so taking part in a clinical trial of newer treatments is often a good option.
Special types of lymphoma
Some types of lymphoma are treated differently enough to be mentioned separately.
Primary central nervous system (CNS) lymphoma
This lymphoma begins in the brain or spinal cord. It often develops in older people or those with immune system problems caused by AIDS or drugs given to keep transplanted organs from being rejected.
Most patients are treated with chemo and/or radiation. One problem with treating this disease is that most chemo drugs commonly used to treat lymphoma don’t reach the brain when given intravenously (IV). For people in reasonably good health, high IV doses of the drug methotrexate have been shown to be the most effective treatment. This is given along with the drug leucovorin and IV fluids, which help limit serious side effects. Other chemo drugs, such as cytarabine, may be added. Rituximab may be added as well. For those who aren’t able to tolerate this treatment, other, less intensive chemo regimens or radiation therapy alone may be tried.
One problem with radiation therapy, especially in older patients, is that it often causes mental changes. Doctors limit the dose of radiation to try to lessen this problem.
If CNS lymphoma keeps growing or comes back after treatment, further options may include chemo (using different drugs), radiation therapy, or a stem cell transplant if a person is healthy enough.
Historically, the outlook for patients with primary CNS lymphoma has not been as good as for other lymphomas, but this is at least partly related to the fact that they tend to be older or have other serious health problems.
Treatment of lymphoma of the eye (primary intraocular lymphoma) is discussed in our document, Eye Cancer (Melanoma and Lymphoma).
People with HIV infections are at increased risk for lymphoma. Although people with HIV often have aggressive forms of lymphoma such as diffuse large B-cell lymphoma, primary CNS lymphoma, or Burkitt lymphoma, their outlook has improved a great deal in recent years. The use of highly active anti-retroviral therapy (HAART) to treat HIV has helped patients to better tolerate chemo.
The major problem in the past was that patients with HIV infection tended to have low blood cell counts to begin with, which made it hard to treat them with full courses of chemo. This problem has been relieved somewhat by the use of HAART and by the use of drugs to help the patient’s body make new blood cells. Still, doctors give chemo cautiously and monitor blood counts closely.
Most experts believe that the prognosis (outlook) for a person with HIV-associated lymphoma relates at least as much to the HIV infection as to the lymphoma. Modern anti-HIV therapy can often control the immune deficiency in patients with AIDS, so the outlook for those patients who develop lymphoma has improved. The treatment of the lymphoma itself depends on the specific type of lymphoma.
Last Medical Review: 03/27/2013
Last Revised: 07/03/2014