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
- Burkitt lymphoma
- Central nervous system (CNS) lymphoma
- Diffuse large B-cell lymphoma (DLBCL)
- Mantle cell lymphoma (MCL)
- Peripheral T-cell lymphoma (PTCL)
- T-cell lymphoblastic (T-LBL)
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.
For information about relapsed or refractory NHL, click here.
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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).
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 that BL is curable in a significant group of patients when treated with high-dose, multidrug chemotherapy regimens that include central nervous system (CNS) prophylaxis. About 60 to 90 percent of children and young adults with the disease achieve durable remissions if treated timely and appropriately. Older patients with BL have less favorable outcomes than younger patients.
Patients with relapsed or refractory BL are encouraged to participate in clinical trials. Consolidation treatment with a high-dose conditioning therapy and autologous stem cell transplantation (or allogeneic transplantation, if a donor is available) may be considered for patients who achieve remission after their second-line treatment.
Primary CNS lymphoma forms in the brain and/or the spinal cord. It is often a feature of AIDS-associated lymphoma, but most patients in the United States who have primary CNS lymphoma do not have a clear predisposing cause. Secondary CNS lymphoma develops when a lymphoma already present in other parts of the body spreads to the brain and/or the spinal cord. Patients with highly aggressive lymphomas, such as Burkitt lymphoma and DLBCL, are at a higher risk of disease relapse with CNS involvement. So, first-line treatment for these types of lymphoma may include chemotherapy administered directly 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 31 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.
The standard treatment is a combination chemotherapy regimen, either with or without an autologous stem cell transplant. Common treatment regimens include bendamustine plus rituximab; a form of CHOP in which bortezomib is used instead of vincristine; and various regimens Non-Hodgkin Lymphoma I 29 including high-dose cytarabine. The following agents are indicated for relapsed and refractory MCL: acalabrutinib (Calquence®), given by mouth; bortezomib (Velcade®), given by IV or subcutaneous injection; ibrutinib (Imbruvica®), given by mouth; zanubrutinib (BrukinsaTM), given by mouth; and lenalidomide (Revlimid®), given by mouth. Allogeneic transplantation with a standard or reduced-intensity conditioning regimen may be considered for patients with relapsed and refractory MCL who achieve remission following second-line therapy.
To read more about mantle cell lymphoma and treatment options, download or order LLS's free fact sheet Mantle Cell Lymphoma Facts.
Peripheral T-cell lymphomas (PTCLs) are a group of rare and often fast-growing non-Hodgkin lymphomas that develop from mature T cells and natural killer (NK) cells. They account for approximately 10 percent of non Hodgkin’s lymphoma cases. Some subtypes include:
- Peripheral T-cell lymphoma, not otherwise specified (PTCL NOS)—This is the most common subtype of PTCL, accounting for about 30 percent of PTCL cases. It most often appears in the lymph nodes, but it can also affect the liver, bone marrow, gastrointestinal tract and the skin.
- Anaplastic large-cell lymphoma (ALCL)— This accounts for about 12 percent of PTCL cases. It can appear throughout the body (systemic) or a specific variant called primary cutaneous ALCL that mainly or only affects the skin, known as Primary Cutaneous Anaplastic Large Cell Lymphoma (pcALCL).
- Angioimmunoblastic T-cell lymphoma (AITL)—One of the most common types in the US and Europe. It is associated with B cells infected with the Epstein-Barr virus.
- 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.
- Adult T-Cell Leukemia/ Lymphoma (ATLL)—This is a rare and aggressive type of PTCL that is associated with the human T-cell lymphotropic virus-1 (HTLV-1).
- Enteropathy-associated T-cell lymphoma (EATL)—This T-cell lymphoma frequently develops in the small bowel of patients with untreated celiac disease.
- Monomorphic Epitheliotropic Intestinal T-cell Lymphoma (MEITL)—This is a lymphoma of the gastrointestinal tract that is NOT associated with celiac disease.
- Hepatosplenic T-cell lymphoma (HSTCL)—This uncommon subtype of PTCL generally affects young men.
- Subcutaneous Panniculitis-like T-cell Lymphoma (SPTCL)— This is a very rare form of skin lymphoma that occurs primarily in the subcutaneous fat tissue, where it causes nodules to form.
- Primary Cutaneous gamma/delta T-cell lymphoma (PCGDTCL)—This is a very rare and aggressive skin lymphoma.
Once you learn that you have PTCL, you need to decide where to get treatment. A PTCL diagnosis is associated with a wide range of outcomes, so it is essential to seek treatment in a center with doctors experienced in caring for patients who have PTCL.
For most newly diagnosed cases of PTCL, the initial treatment is usually combination chemotherapy. Clinical trials are underway to study the efficacy and safety of potential new drugs and drug combinations to treat PTCL.
For more information about PTCL and treatment options, download or order LLS's free fact sheet Peripheral T-Cell Lymphoma.
Patients with this diagnosis are treated in the same way as patients with acute lymphoblastic leukemia (ALL). To read more about treatment options, download or order LLS's free fact booklet Acute Lymphoblastic Leukemia.