Surgery
Because lymphoma spreads throughout the lymph system, surgery plays little role. However, in primary extranodal tumors, such as those arising in the spleen or stomach, surgical removal may be useful.  In localized lymphomas of the skin, surgical excision is usually first-line treatment.

Chemotherapy
Chemotherapy is often an essential component of lymphoma treatment, as a systemic approach is necessary to kill cells circulating throughout the lymphatic system .Chemotherapy is usually given in cycles, starting with treatment over several days. It is then followed by a few weeks without treatment so that the patient can recover from side effects, particularly anemia and low white blood cells. The sequence is then repeated until the disease is in remission and then continued to extend remission.

Chemotherapy drugs used for lymphoma may include combinations of the following:

• bleomycin (Blenoxane®)
• cyclophosphamide (Cytoxan®)
• dacarbazine (DTIC-Dome®)
• daunorubicin
• doxorubicin (Adriamycin®)
• etoposide (VP-16, VePesid®)
• mechlorethamine (Mustargen®, a.k.a. nitrogen mustard)
• prednisone
• procarbazine (Matulane®)
• vinblastine (Velban®)
• vincristine (Oncovin®)

Hodgkin’s lymphoma
The following combination chemotherapy protocols are used widely in Hodgkin’s lymphoma:

• ABVD: doxorubicin, bleomycin , vinblastine and dacarbazine
• BEACOPP: bleomycin , etoposide, doxorubicin, cyclophosphamide , vincristine , procarbazine and prednisone
• MOPP: mechlorethamine , vincristine , procarbazine and prednisone

ABVD and MOPP are long-established, while BEACOPP is a newer regimen. BEACOPP, with its seven different components, may have increased side effects, but has also shown favorable treatment outcomes, particularly in higher-stage disease versus other protocols.

Non-Hodgkin’s Lymphoma
Perhaps the most common combination chemotherapy protocol for non-Hodgkin’s lymphomas is CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). However, there are numerous other combination protocols.  Because there are many varieties of non-Hodgkin’s lymphoma, there may be specific treatments applicable to a particular type.

Immunotherapy
Some patients with non-Hodgkin’s lymphoma, especially B cell lymphoma, are often treated with antibodies that have specific activity against the tumor.  These antibodies can work alone or can be given in combination with drugs to enhance the efficacy of chemotherapy. Common monoclonal antibody treatments include:

• Rituxan® (rituximab)
• Bexxar® (tositumomab)
• Zevalin® (ibritumomab tiuxetan)

Radioimmunotherapy
City of Hope has developed novel ways of delivering radiation utilizing monoclonal antibodies, part of the immune system, which have been combined with small amounts of radioactive substances. These radiolabeled antibodies allow doctors to target lymphoma cells directly while minimizing damage to normal tissues.   City of Hope was one of the first programs to use radioimmunotherapy as part of a transplant regimen to improve the safety and efficacy of the treatment.

Adoptive T-Cell Therapy
T-cells are a powerful part of the immune system. A new approach being studied at City of Hope involves redirecting T-cells to recognize cancer cells specific to lymphoma. Researchers are taking normal T-cells from patients with lymphoma, and genetically modifying them to target and destroy the malignant cells. Studies are focusing on patients with recurrent diffuse large cell lymphoma who are undergoing ASCT.
 
Stem Cell Transplantation
Hematopoietic Cell Transplantation (HCT) and Peripheral Blood Stem Cell Transplantation (PBSCT) are therapies that use stem cells (immature blood cells) to treat a patient's malignancy, or to repair diseased or defective bone marrow.  Transplants are sometimes performed early in the course of treatment to improve long-term results. In some patients, it is utilized when other treatments are not working.

Transplant procedures include intensive chemotherapy with or without radiation therapy to destroy (ablate) the cancerous cells, followed by an infusion of healthy new cells.

Autologous Stem Cell Transplantation (ASCT)
The greatest concern for patients with lymphoma is the chance that the disease will return (relapse). The Division of Hematology and Hematopoietic Cell Transplantation at City of Hope pioneered the use of early autologous stem cell transplantation (ASCT) in patients with poor-risk, aggressive NHL to avoid relapse after initial treatment.  It is also the most effective treatment for most patients who suffer a recurrence of their lymphoma or Hodgkin’s disease.

In autologous transplants, a patient donates and receives back his or her own stem cells, typically collected from peripheral (circulating) blood.

• ASCT in AIDS-related Lymphoma and Hodgkin’s Lymphoma

At City of Hope, patients with AIDS-related lymphoma and Hodgkin’s lymphoma are sometimes candidates for ASCT and the results of treatment at City of Hope are excellent.  We are also conducting studies of autologous stem cells that have been genetically engineered to provide additional resistance to HIV infection in patients undergoing ASCT.  This approach is being studied here at City of Hope to help improve the control of the virus after transplant.

Allogeneic Transplantation
In certain situations, a patient’s lymphoma is very advanced, and the blood or bone marrow is extensively involved. In these cases, an allogeneic transplant strategy is preferred, using stem cells from a matched donor, using related, unrelated or cord blood.

In allogeneic transplants, the donor is preferably a sibling. Alternatively, a matched unrelated donor (MUD) who has a similar genetic type may be used. In fact, 45 percent of all allogeneic transplants at City of Hope come from volunteer donors who are unrelated to the patient.

Researchers now understand that the response from the immune system carried in transplanted donor stem cells helps fight the cancer.  This is known as a graft versus tumor effect.

Efforts to decrease allogeneic transplant-related complications are being explored, including the use of less intensive "non-myeloablative" transplant conditioning regimens (also called “mini-HCT”) which have a reduced risk of side effects and can be used to treat older patients with lymphoma, leukemia and myeloma.

Radiation Therapy
Radiation therapy uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. Traditionally, lymphoma treatment required the use of whole-body irradiation, which unnecessarily exposes healthy tissues.

City of Hope was the first in the Western U.S. to provide treatment for lymphoma using the helical TomoTherapy System®. This system combines radiation delivery with real-time imaging, allowing doctors to create a higher dose of energy that more precisely targets the bone marrow. The system not only provides more effective treatment, it reduces the unwanted exposure of normal tissues and reduces potential complications.