Aggressive non-Hodgkin lymphoma (NHL) progresses rapidly. It makes up about 60 percent of all NHL cases in the United States. Aggressive subtypes include:
- AIDS-associated lymphoma
- Anaplastic large cell lymphoma
- Burkitt lymphoma
- Central nervous system (CNS) lymphoma
- Diffuse large B-cell lymphoma (DLBCL)
- Hepatosplenic lymphoma
- Mantle cell lymphoma
- Mucosa-associated lymphoid tissue (MALT) lymphoma (transformed)
- Peripheral T-cell lymphoma (most types)
- Transformed follicular lymphoma
The goal of treatment for many subtypes is a cure. Treatment for aggressive NHL starts at the time of diagnosis.
Chemotherapy has often proved to be an effective approach to treating aggressive subtypes. The standard of care for each subtype varies. Below are some examples of specific approaches to therapy:
- Early-stage disease. Treatment can include the combination chemotherapy CHOP or involved field radiation therapy, or both. Sometimes the monoclonal antibody drug rituximab (Rituxan®) is added to the CHOP regimen (R-CHOP).
- Advanced-stage disease. First-line treatment is CHOP with Rituxan (R-CHOP).
- Disease that's spread to other areas or organs. If lymphoma is in the bone marrow, nasal sinuses or testicles or near the spinal cord, there's a risk that it may spread to the central nervous system. In these circumstances, chemotherapy may be given directly into the spinal fluid.
- High-risk disease. Factors associated with a high risk for relapse after standard therapy include high levels or the presence of certain proteins in the blood and the p53 gene mutation. In these cases, a more aggressive initial treatment than normal is needed. A clinical trial can be an effective treatment option.
Treating Specific Aggressive Subtypes
Certain types of NHL are seen more often in people who have autoimmune deficiency syndrome (AIDS), including diffuse large B-cell lymphoma, Burkitt lymphoma and primary central nervous system lymphoma. Treatment outcome depends on how well AIDS is responding to therapy. Because AIDS already leads to low blood cell counts, chemotherapy must be carefully considered to determine whether the treatment's additional effect on blood levels can be managed. Improved treatment for human immunodeficiency virus (HIV) in recent years has helped reduce the number of people diagnosed with AIDS-associated NHL.
Anaplastic large cell lymphoma, most common in young people, usually starts in lymph nodes and can spread to the skin. But it can also start in the skin. A combination of radiation therapy and chemotherapy has proved to be an effective two-pronged approach to treating this subtype. Brentuximab vedotin, (Adcetris(R)) also known as SGN-35, is FDA approved for the treatment of patients with systemic anaplastic large cell lymphoma (ALCL) after failure of at least one prior multi-agent chemotherapy regimen. Brentuximab vedotin is administered by injection. About 80 percent of anaplastic large cell lymphoma patients are cured. The combination therapy is most effective if a patient's tumor cells contain a protein called ALK-1.
This B-cell subtype is considered to be highly aggressive. It usually appears as a lymphoma mass in the abdominal (stomach) area. It can also appear in bone marrow, blood, the central nervous system and other organs. Burkitt lymphoma, named after the surgeon who first identified the disease in children in Africa, mostly affects older adults. In Africa, the disease usually appears in children as a mass in a facial bone, especially the jaw. Doctors typically use chemotherapy to treat the disease. Drugs used include prednisone, cyclophosphamide (Cytoxan®), vincristine (Oncovin®), cytarabine (Cytosar-U®, cytosine arabinoside, ara-C), doxorubicin (Adriamycin® PFS, Adriamycin®) and methotrexate (Rheumatrex®, Trexall®).
There are two types of this rare central nervous system (CNS) lymphoma: primary and secondary. Primary CNS lymphoma starts in the brain or spinal cord and is an AIDS-associated lymphoma, although it may be related to other NHL subtypes as well. Secondary CNS lymphoma starts in another area of the body and spreads to the brain and/or spinal cord. Researchers are currently studying effective treatments for both types in clinical trials. Standard treatment may include chemotherapy, glucocorticosteroid drugs and/or radiation therapy. Treatment in clinical trials includes immunotherapy and high-dose chemotherapy with stem cell transplantation.
Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive NHL subtype, making up about 30 percent of all NHL cases in the United States. It affects mostly middle-aged and older adults. Although it falls into the aggressive category, DLBCL can sometimes start out as an indolent lymphoma, such as small B-cell lymphoma or a follicular lymphoma. The chemotherapy regimen R-CHOP has proved successful in curing 50 percent to 60 percent of patients with DLBCL and is the standard of care for advanced-stage disease.
This type of T-cell lymphoma is an extremely rare and aggressive disease that starts in the liver or spleen and usually affects young adults in their 20s and 30s. Treatment for patients with hepatosplenic T-cell lymphoma includes anthracycline-based chemotherapy and, in some cases, stem cell transplantation. See Disease Registries and Other Disease Studies for information about a study that is currently under way.
By the time mantle cell lymphoma is diagnosed, it's usually already widespread in the lymph nodes and bone marrow and sometimes in the liver, intestines and spleen. NHL develops in a lymphocyte in an area of a lymph node known as the mantle zone. Mantle cell lymphoma is most commonly diagnosed in men older than 50. Doctors typically treat mantle cell lymphoma with chemotherapy drugs and the monoclonal antibody rituximab (Rituxan®).
To read more about mantle cell lymphoma and treatment options, download or order The Leukemia & Lymphoma Society's (LLS's) free fact sheet Mantle Cell Lymphoma Facts.
Mucosa-associated lymphoid tissue (MALT) lymphoma, which affects sites outside the lymph nodes such as the gastrointestinal tract, eyes, thyroid gland, salivary glands, lungs or skin, and represents about 7.5 percent of NHL cases. Patients with MALT lymphoma may have a history of autoimmune disease. A higher incidence of MALT lymphoma involving the stomach is seen in patients who have been infected with the bacterium Helicobacter pylori (H. pylori). Bacteria have also been implicated in other forms of MALT lymphoma. Treatment often includes potent combinations of antibiotics, which both eradicate the H. pylori infection and cause the lymphoma to regress. Many patients with H. pylori have been cured of MALT lymphoma without radiation or chemotherapy.
Transformed MALT lymphoma is an aggressive lymphoma and is uncommon. For this small subset of patients, MALT lymphoma can transform into diffuse large B-cell lymphoma (DLBCL). These patients have shown to benefit from treatments used for DLBCL. See Diffuse Large B-cell Lymphoma (above).
Peripheral T-cell lymphoma is one of the most difficult lymphomas to treat. There are several forms of this subtype:
- Acute adult T-cell lymphoma (the most common)
- Extranodal T-cell or natural killer-cell (NK-cell) lymphoma
- Nasal type lymphoma, which often affects the upper-airway passages, such as the nose and nasopharynx, and skin and digestive tract
- Enteropathy type T-cell lymphoma, which can affect people sensitive to gluten
- Subcutaneous panniculitis-like T-cell lymphoma, which invades the skin's deepest levels, causing nodules to form under the skin
Peripheral T-cell lymphoma is usually treated like diffuse large B-cell lymphoma, usually with R-CHOP. However, studies are under way to develop more effective treatment approaches.
For more information about peripheral T-cell lymphoma and treatment options, download or order LLS's free fact sheet Peripheral T-Cell Lymphoma Facts.
Follicular lymphoma starts out as an indolent NHL subtype. However, it often transforms to an aggressive large B-cell lymphoma. High-dose chemotherapy followed by autologous stem cell transplantation can be an effective treatment to manage the disease.
A clinical trial can also be a good option for follicular lymphoma patients whose disease has transformed despite several different treatment approaches having been tried. Other treatment choices are:
- Chemotherapy with or without the monoclonal antibody rituximab (Rituxan®).
- A radioimmunotherapeutic monoclonal antibody such as Zevalin®
- Radiation therapy
- Supportive care
- Combination chemotherapy with Rituxan and possibly radiation therapy for patients whose FL transformed before a significant amount of treatment and is in a single area
- Autologous stem cell infusion (in a clinical trial)
Treatment options for indolent FL and factors that affect treatment outcome are described in Treatment for Indolent NHL Subtypes.