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Non-Hodgkin's lymphoma

Description

An in-depth report on the causes, diagnosis, and treatment of non-Hodgkin's lymphoma.

Alternative Names

Lymphoma - non-Hodgkin's; NHL; B-cell lymphomas

Staging and Treatment Guidelines

General Approach for Treating Non-Hodgkin's Lymphoma

Treatment for non-Hodgkin's lymphoma is highly specific for each patient and is determined by the tumor classification. It includes the following factors:

• Stage
• Grade
• Histologic type (cellular structure)
• Location
• Other factors, such as blood levels of lactate dehydrogenase

Treatment for lymphomas has been primarily dependent on chemotherapy (particularly intensive regimens using several drugs) or a combination of chemotherapy and radiation. For advanced or refractory lymphomas and for relapse, patients may undergo bone marrow or stem cell transplantation. New treatments, especially those known as immunotherapies, or biological response modifier (BRM) therapies, are showing promise. Some experts recommend that patients ask their doctors about getting into well-designed clinical trials as early as possible.

Assessing Treatment Success

In assessing the success of a clinical trial, experts often refer to the tumor response . A complete response, for example, means that there is no longer any evidence at all of the disease by examination, blood tests, or x-ray studies. It does not necessarily mean, however, that the disease is cured. It may still recur later on.

In judging the success of a treatment for NHL, the most important criteria are overall survival and the duration of time until the disease progresses or the patient dies.

Early Stage Lymphomas (Stage I and Stage II)

In Stage I, lymphoma is found in only one lymph node area or in only one area or organ outside the lymph nodes. Either of the following indicates stage II:

• Lymphoma is found in two or more lymph node areas on the same side of the diaphragm.
• Lymphoma is found in only one area or organ outside the lymph nodes and in the lymph nodes around it. Other lymph node areas on the same side of the diaphragm may also have lymphoma.

Early Stage Indolent (Low-Grade) Lymphoma. Below are the general treatment options:

• Radiation therapy. Radiation to local areas can achieve a cure in 40 - 50% of patients.
• Chemotherapy. Chemotherapy uses drugs to kill cancer cells.
• Watchful waiting. Patients who choose watchful waiting must be aware of signs and conditions indicating the need for treatment. These include B symptoms, endangered organs, massive bulky tumors, or a steady progression that lasts at least 6 months.
• Investigative treatments such conjugated and unconjugated monoclonal antibodies or radiation plus chemotherapy. In one study, a combination of therapies worked better than radiation alone.

The following are treatment options for some specific low-grade lymphomas:

• Mucosa-associated lymphoid tissue (MALT) lymphoma. When disease is in the stomach (gastric MALT) and the patient is infected with H. pylori bacteria, antibiotics can cause regression in a significant number of patients with stage I lymphoma. In certain patients where antibiotics fail, or are not appropriate, radiation alone can achieve significant cure rates. Surgery with or without radiation, or chemotherapy with or without radiation are possible options. Treatment options for patients with MALT localized in other sites depend on the location of the specific disease, ranging from radiation to chemotherapy to biologic therapies, such as interferon.
• Primary gastric lymphoma (indolent). Radiation is the typical treatment for this lymphoma, which is located only in the stomach, small intestine, or other nearby regions. Surgery is being reconsidered since it seems to offer no advantage.

Early Stage Aggressive (Intermediate- to High-Grade) Lymphomas. Treatment options include:

• Chemotherapy alone
• Combinations of chemotherapy (usually CHOP) plus radiation therapy
• Radiation alone (rarely)
• Chemotherapy alone or with surgery for lymphoma in the gastrointestinal region
• Immunotherapies (rituximab, Bexxar) with or without chemotherapy (usually CHOP), or high dose chemotherapy and bone marrow or stem cell transplantation

Advanced Stage Lymphomas (Stage III and IV)

In stage III, lymphoma is found in lymph node areas on both sides of the diaphragm (for instance, in both the chest and the abdomen). The lymphoma may also have spread to the spleen. In stage IV, lymphoma has spread via the bloodstream to organs outside the lymph system, such as the bone marrow or brain. Lymphoma cells may or may not be in the lymph nodes near these organs.

Advanced Stage Indolent (Low-Grade Lymphomas). Treatment options are controversial because of the low-cure rate and yet slow-growing nature of these lymphomas. Patients without symptoms are often managed by watchful waiting, in which the disease is monitored closely for development of symptoms or bulky tumor masses, particularly if they threaten major organs. At such times, treatment is started. Treatment may include:

• Chemotherapy combinations (CHOP, CVP, C[M]OPP)
• Nucleoside analogs (for example, fludarabine) alone or with chemotherapy
• Oral alkylating chemotherapy drugs such as cyclophosphamide or chlorambucil with or without steroids
• Monoclonal antibodies (MAbs) such as rituximab alone or in combinations with CHOP or nucleoside analogs
• Chemotherapy plus interferon
• Clinical trials involving intensive chemotherapy and radiation followed by bone marrow or stem cell transplantation

Advanced Stage Aggressive (Intermediate- to High-Grade) Lymphomas. Treatment options may include:

• Doxorubicin-based combination chemotherapy with or without rituximab
• Chemotherapy plus radiation therapy
• Immunotherapies with or without chemotherapy
• Treatments to prevent disease from spreading to central nervous system in high-risk patients
• Clinical trials for patients at high risk for relapse that involve intensive chemotherapy, high dose chemotherapy, and bone marrow or stem cell transplantation

Relapsed or Refractory (Nonresponsive to Treatment) Non-Hodgkin's Lymphoma

Indolent-Lymphomas Relapses. Nearly all patients with indolent lymphomas relapse after initial treatment, with duration of remissions after a first treatment averaging 18 - 50 months. Successful retreatment is often possible, but disease-free periods become increasingly shorter with each subsequent treatment.

Older patients may choose watchful waiting. Other treatment options may include:

• Radiation alone or with chemotherapy -- in one study low-dose involved-field radiotherapy was very effective in recurring indolent lymphoma.
• Chemotherapy
• High-dose chemotherapy with autologous stem cell transplant
• Clinical trials involving monoclonal antibodies, radioimmunotherapy, nucleoside analogues alone or in combination with other drugs, or stem cell transplantation followed by biologic therapies

Aggressive Lymphomas Relapse. After initial treatment, more than half of patients with aggressive lymphomas are cured, while about 20% progress and the other 30% relapse after a disease-free period. Among those who relapse, many can still be cured with aggressive treatments.

Treatment options:

• Bone marrow or peripheral stem cell transplantation
• Bone marrow transplantation with radiation
• Clinical trials that involve continuous infusion chemotherapy, biologic therapies (monoclonal antibodies) alone or in combination with transplantation

Preventing and Treating Lymphomas in the Central Nervous System

Treating Lymphoma Restricted to the Central Nervous System. Treatment options may include:

• High-dose methotrexate regimens alone or in combination with radiation
• Corticosteroids and radiation
• Clinical trials that involve biologic therapies, such as rituximab or interferon alpha administered directly into the spinal fluid (intrathecal administration) for meningitis related to central nervous system lymphoma

Preventing (Prophylactic Treatment) Lymphomas in High-Risk Patients. Treatment to prevent the spread of NHL to the central nervous system may be appropriate in some patients. It is not recommended for patients with low-grade NHL. Preventive treatment may be appropriate for certain patients with high-grade NHL, such as those with lymphoblastic and Burkitt's lymphoma or if they have 4 - 5 of the following risk factors: Elevated levels in the blood of the enzyme acetate dehydrogenase and albumin (a common protein), being older than 60, and having lymph nodes beyond the peritoneum (the lining of the abdomen) and involvement of more than one site outside a lymph node.

• Review Date: 1/17/2007
• Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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