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
- Angioimmunoblastic Lymphoma
- Burkitt lymphoma
- Central nervous system (CNS) lymphoma
- Diffuse large B-cell lymphoma (DLBCL)
- Mantle cell lymphoma (MCL)
- Peripheral T-cell lymphoma (PTCL)
Patients with fast-growing NHL are frequently treated with chemotherapy that consists of four or more drugs. In most cases, this is the combination therapy called R-CHOP (rituximab [Rituxan®], cyclophosphamide [Cytoxan®], doxorubicin [hydroxydoxorubicin], Oncovin® [vincristine] and prednisone). This intensive, multidrug chemotherapy can be very effective for aggressive lymphoma, and cures have been achieved. Chemotherapy can be supplemented by radiation therapy in select cases, for instance, when large NHL masses are found during the diagnostic and staging process.
The types of NHL that are most often seen in people with acquired immune deficiency syndrome (AIDS) are diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma and primary central nervous system (CNS) lymphoma. Treatment outcomes depend on how well the patient with AIDS responds to therapy and manages the effects of chemotherapy on blood counts. Because AIDS already leads to low blood cell counts, chemotherapy must be carefully considered to determine whether the chemotherapy's additional effects on blood levels can be managed. The number of people developing AIDS-associated NHL has decreased in the last several years because of improved treatment of HIV (the virus that can lead to AIDS).
Patients with this diagnosis are treated in the same way as patients with acute lymphoblastic leukemia (ALL).
This aggressive B-cell subtype grows and spreads very quickly. It may involve the jaw, bones of the face, bowel, kidneys, ovaries, bone marrow, blood, central nervous system (CNS) and other organs. Burkitt lymphoma may spread to the brain and spinal cord (part of the CNS), therefore, treatment to prevent CNS spread should be included in any treatment regimen. Doctors typically use highly aggressive chemotherapy to treat this subtype of NHL. Commonly used regimens include:
- CODOX-M/IVAC (cyclophosphamide, vincristine [Oncovin®], doxorubicin and high-dose methotrexate) alternating with IVAC (ifosfamide, etoposide and highdose cytarabine)
- Hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin [Adriamycin®] and dexamethasone) alternating with methotrexate and cytarabine). In small studies, rituximab was used in combination with hyper-CVAD.
- DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine [Oncovin®], cyclophosphamide, doxorubicin plus rituximab)
Studies report an 80 to 90 percent survival rate among adults with Burkitt lymphoma who are treated with the aggressive chemotherapy regimens listed. Patients who do not respond to an intensive regimen are encouraged to participate in clinical trials.
There are two types of central nervous system (CNS) lymphoma: primary and secondary. Primary CNS lymphoma starts in the brain and/or the spinal cord. It is often a feature of 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. Patients with highly aggressive lymphomas, such as Burkitt lymphoma, DLBCL and PTCL, are at a higher risk of CNS relapse. Thus, first-line treatment for these types of lymphoma may include chemotherapy given into the spinal fluid.
Both primary and secondary CNS lymphomas are uncommon. Standard treatment may include chemotherapy that includes intrathecal methotrexate, corticosteroid drugs and/or radiation therapy. Immunotherapy and high-dose chemotherapy with stem cell transplantation are being studied in clinical trials. Read more>>
Diffuse large B-cell lymphoma (DLBCL) is the most common NHL subtype, making up about 30 percent of all NHL cases in the United States. It grows rapidly in the lymph nodes and frequently involves the spleen, liver, bone marrow or other organs. Usually, DLBCL development starts in lymph nodes in the neck or abdomen and is characterized by masses of large B cells. In addition, patients with DLBCL often experience B symptoms (fever, night sweats and loss of more than 10 percent of body weight over 6 months).
For some patients, DLBCL may be the initial diagnosis. For other patients, an indolent lymphomas such as small lymphocytic lymphoma or follicular lymphoma transform and become DLBCL. Treatments include
- R-CHOP (rituximab [Rituxan®], cyclophosphamide [Cytoxan®], doxorubicin [hydroxydoxorubicin], Oncovin® [vincristine] and prednisone).
- Dose adjusted EPOCH-R,(dose-adjusted etoposide, prednisone, vincristine [Oncovin®], cyclophosphamide, hydroxydoxorubicin [doxorubicin] plus rituximab.
- Rituximab and hyaluronidase human (Rituxan HycelaTM)
Mantle cell lymphoma (MCL) originates from a lymphocyte in the mantle zone of the lymph node. It begins in the lymph nodes and spreads to the spleen, blood, bone marrow and sometimes the esophagus, stomach and intestines. Some patients do not show signs or symptoms of the disease, so delaying treatment may be an option for them. Most patients need to start treatment after diagnosis.
Treatment will depend on several factors, which include
- The patient’s age
- The patient’s fitness
- The presence of symptoms
- The patient’s MCL International Prognostic Index (MIPI) risk category
- Proliferative index
- Cell variant
- Additional—as yet unknown—factors (genetic anomalies)
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.
Peripheral T-cell lymphoma (PTCL) refers to a group of aggressive NHL subtypes that originate in mature T-cell lymphocytes. The most common subtypes include:
- Peripheral T-cell, not otherwise specified (PTCL NOS) - This is the most common subtype of PTCL. It often involves lymph node sites but can also involve other areas such as the liver, bone marrow, gastrointestinal track and skin.
- Anaplastic Large Cell Lymphoma (ALCL) - This subtype usually starts in the lymph nodes and can spread to the skin. There are two main subtypes of ALCL:
- Systemic ALCL (sALCL)
- Systemic ALCL ALK-1 positive - About 80 percent of patients with this subtype are cured. This disease is more common in young people.
- Systemic ALCL ALK-1 negative - This subtype occurs mainly in older patients. Treatment with chemotherapy or radiation therapy is often less successful and a stem cell transplant may be discussed.
- Primary cutaneous anaplastic large cell lymphoma (pcALCL) - This subtype mostly affects the skin, but other parts of the body may be involved.
- Systemic ALCL (sALCL)
- Hepatosplenic T-cell lymphoma - This uncommon subtype of PTCL starts in the liver and spleen and usually affects young men.
- Angioimmunoblastic T-cell lymphoma - This type of T-cell lymphoma often involves lymph nodes and the bone marrow and is generally associated with viral infection. Many patients have “paraneoplastic symptoms” including fevers, rashes and abnormal protein levels in their blood.
- Enteropathy-type intestinal T-cell lymphoma (EATL)- This subtype develops in the small bowel of patients with untreated celiac disease.
- Extranodal natural killer/T-cell lymphoma (ENK/TCL) - This is an uncommon type of lymphoma that can occur in the nasal sinuses or in other parts of the body. It is usually a very aggressive lymphoma that requires both chemotherapy and radiation.
PTCL is commonly treated with the regimens used for diffuse large B-cell lymphoma (DLBCL). CHOP (cyclophosphamide [Cytoxan®], doxorubicin [hydroxydoxorubicin], vincristine [Oncovin®], and prednisone) is the standard treatment for newly diagnosed PTCL; however, the treatment outcomes are not as favorable as they are for DLBCL. The following drugs have also been approved for the treatment of PTCL:
- Pralatrexate (Folotyn®)
- Romidepsin (Istodax®)
- Brentuximab vedotin (Adcetris®)
- Belinostat (Beleodaq®)
For more information about PTCL and treatment options, download or order LLS's free fact sheet Peripheral T-Cell Lymphoma Facts.