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Lymphomas (Non-Hodgkin's)

Description

An in-depth report on the causes, diagnosis, and treatment of 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 classification and includes the following factors:

  • Stage.
  • Grade.
  • Histologic type (its 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 physicians about getting into well-designed clinical trials as early as possible.

Bone marrow - series Click the icon to see an illustrated series detailing bone marrow transplant surgery.

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; or 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. General treatment options. 1. Radiation therapy to local areas can achieve a cure in 40% to 50% of patients. 2. Chemotherapy or watchful waiting in some circumstances. (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 six months.) 3. Investigative treatments: conjugated and unconjugated monoclonal antibodies; radiation plus chemotherapy (in one study, combined modality was more effective 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 stage 1 patients. In patients where antibiotics fail, (or are not felt to be appropriate), radiation alone can achieve significant cure rates in certain patients. 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). (Located only in the stomach, small intestine, or other nearby regions.) Radiation. Surgery being reconsidered since it seems to offer no advantage.
Click the icon to see an image of the digestive system.

Early Stage Aggressive (Intermediate- to High-Grade) Lymphomas. Treatment options 1. Chemotherapy alone. 2. Combinations of chemotherapy (usually CHOP) plus radiation therapy (combined modality). 3. Radiation alone (rarely). 4. Chemotherapy alone or with surgery for lymphoma in the gastrointestinal region. 5. Clinical trial of immunotherapies (e.g., rituximab) with or without chemotherapy (usually CHOP). 6. A clinical trial of high dose chemotherapy and bone marrow or stem cell transplantation. (It is not yet clear if there is an advantage to these treatments over high-dose chemotherapy.)

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: 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. 1. Chemotherapy combinations (CHOP, CVP, C[M]OPP). 2. Nucleoside analogs (e.g., fludarabine) alone or with chemotherapy. 3. Oral alkylating chemotherapy agents (e.g., cyclophosphamide, chlorambucil) with or without steroids. 4. Monoclonal antibodies (MAbs) (.e.g., rituximab) alone or in combinations with CHOP or nucleoside analogs. 5. Chemotherapy (e.g., CHOP) with interferon. 6. Clinical trials: Intensive chemotherapy and radiation followed by bone marrow or stem cell transplantation; antisense RNA.

Advanced Stage Aggressive (Intermediate- to High-Grade) Lymphomas. Treatment options. 1. Doxorubicin-based combination chemotherapy (e.g., CHOP) with or without rituximab. 2. Chemotherapy plus radiation therapy. 3. Clinical trials for patients at high risk for relapse: intensive chemotherapy; high dose chemotherapy and bone marrow or stem cell transplantation; immunotherapies (e.g., various monoclonal antibodies) with or without chemotherapy (e.g., CHOP).4. Treatments to prevent disease from spreading to central nervous system in high-risk patients.

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 to 50 months. Successful retreatment is often possible, but disease-free periods become increasingly shorter with each subsequent treatment.

Treatment options: Older patients may choose watchful waiting. 1. Radiation alone or with chemotherapy. In one study low-dose involved-field radiotherapy was very effective in recurring indolent lymphoma. 2. Chemotherapy (single agents of combinations). 3. High-dose chemotherapy with autologous stem cell transplant. 4. Clinical trials, including monoclonal antibodies, radioimmunotherapy, nucleoside analogues alone or in combination with other agents, stem cell transplantation followed by biologic therapies.

Aggressive Lymphomas Relapse. After initial treatment, more than half 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: 1. Bone marrow or peripheral stem cell transplantation. 2. Clinical trials: continuous infusion chemotherapy, biologic therapies (monoclonal antibodies) alone or in combination with transplantation; bone marrow transplantation with radiation.

Bone-marrow transplant - series Click the icon to see an illustrated series detailing bone marrow transplant surgery.

Preventing and Treating Lymphomas in the Central Nervous System

Treating Lymphoma Restricted to the Central Nervous System. Treatment options: 1. High-dose methotrexate regimens alone or in combination with radiation. Note: a 2002 major trial indicates that the combination improves survival although it is very toxic. 2. Corticosteroids and radiation. 3. Clinical trials: biologic therapies, e.g., 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 four or five 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.

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