Non-Hodgkin lymphoma medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Treatment for non-Hodgkin's lymphoma depends on the stage of the disease, the type of cells involved, whether they are indolent or aggressive, and the age and general health of the patient.

Non-Hodgkin's lymphoma is often treated by a team of specialists that may include a hematologist, medical oncologist, and/or radiation oncologist. Non-Hodgkin's lymphoma is usually treated with chemotherapy, radiation therapy, or a combination of these treatments. In some cases, bone marrow transplantation, biological therapies, or surgery may be options. For indolent lymphomas, the doctor may decide to wait until the disease causes symptoms before starting treatment. Often, this approach is called "watchful waiting."

Taking part in a clinical trial (research study) to evaluate promising new ways to treat non-Hodgkin's lymphoma is an important option for many people with this disease.

Medical Therapy

Medical therapy for Non-Hodgkin lymphoma

Stage	Watchful waiting	Chemotherapy	Radiotherapy	Biological therapy	Stem cell transplant
Indolent Lymphoma
Limited stage	Offered to patients who do not have symptoms	Offered if patients cannot have radiation therapy If lymphoma is causing symptoms	External beam radiation therapy is used most often	May be offered along with chemotherapy Rituximab is used most often Only used for B-cell lymphomas	---------
Advanced stage	Offered to patients who do not have symptoms	Offered to patients who have symptoms Single Drug Regimen: Chlorambucil OR Fludarabine OR Cyclophosphamide Combination Drug Regimen: (CVP) Cyclophosphamide AND Vincristine AND Prednisone	May also be given to specific areas to control symptoms	May be offered	---------
Recurrent	---------	Single Drug Regimen: Fludarabine Combination Drug Regimen: (CHOP) Cyclophosphamide AND Doxorubicin AND Vincristine AND Prednisone (CVP) Cyclophosphamide AND Vincristine AND Prednisone (FND) Fludarabine AND Mitoxantrone AND Dexamethasone	May be given to relieve pain or to control the symptoms	May be offered	May be offered
Aggressive Lymphoma
Limited stage	----------	Chemotherapy is usually the main treatment Combination Drug Regimen: (CHOP) Cyclophosphamide AND Doxorubicin AND Vincristine AND Prednisone	Radiation therapy is usually given after chemotherapy Used if the lymphoma is localized in one area of the body	Rituximab is used most often Used in combination with chemotherapy	----------
Advanced stage	----------	Combination Drug Regimen: (CHOP) Cyclophosphamide AND Doxorubicin AND Vincristine AND Prednisone CNS Prophylaxis: Drug Regimen (Intrathecal or Intravenously): Methotrexate OR Cytarabine To treat primary CNS lymphoma As preventive for lymphomas that tend to spread to the CNS: Lymphoma that involves paranasal sinuses or the testicles Very aggressive lymphomas, such as Burkitt lymphoma or lymphoblastic lymphomas	May be offered	May be offered	May be considered
Recurrent	---------	Combination Drug Regimen: (DHAP) Dexamethasone AND Cytarabine AND Cisplatin (EPOCH) Etoposide AND Prednisone AND Vincristine AND Cyclophosphamide AND Doxorubicin (ESHAP) Etoposide AND Methylprednisolone AND Cytarabine AND Cisplatin (GDP) Gemcitabine AND Dexamethasone AND Cisplatin (ICE) Ifosfamide AND Cisplatin AND Etoposide (mini-BEAM) Carmustine AND Etoposide AND Cytarabine AND Melphalan	---------	May be offered	May be recommended

Chemotherapy

• Chemotherapy may be used:

• As the primary treatment, with or without radiation therapy, to destroy cancer cells

• Alone or along with biological therapy or radiation therapy, depending on the type and stage of Non-Hodgkin lymphoma
• Early stage, slow-growing (indolent) lymphomas may be treated with radiation therapy by itself or with chemotherapy (single drugs or a combination of drugs) or biological therapy, if the person has symptoms
• Fast-growing (aggressive) lymphomas are usually treated immediately with combination chemotherapy and biological therapy (with or without radiation therapy). This treatment offers the best chance of success

• In people with a lymphoma that tends to spread to the brain and spinal cord
• In combination with biological therapy or radiation therapy to treat recurrent or relapsed lymphoma
• To relieve pain or to control the symptoms of advanced Non-Hodgkin lymphoma (palliative chemotherapy)

Radiation therapy

Radiation may be used for Non-hodgkin lymphoma:

• As the main treatment for early stage (stage I or sometimes stage II) indolent Non-Hodgkin lymphoma

• Radiation therapy may be used when Non-Hodgkin lymphoma is in 1 or 2 lymph node areas in the same part of the body
• Early stage Non-Hodgkin lymphoma often responds very well to radiation therapy

• With chemotherapy to destroy lymphoma cells

• Radiation therapy is often given with chemotherapy, either after or along with chemotherapy, to help destroy lymphoma cells and to reduce the risk of the cancer recurring
• Radiation therapy to certain areas is usually combined with chemotherapy to treat aggressive lymphomas or for large tumors

• To relieve pain or to control the symptoms of advanced lymphoma (palliative radiation therapy)

• Radiation can be used to shrink tumors that are pressing on or spreading into other organs or structures
• It can also be used to shrink enlarged lymph nodes and relieve symptoms caused by tumors

External beam radiation therapy

• Radiation therapy treatment is usually given each day for 5 days a week, the dose and schedule for the radiation therapy is determined by:

• The type of Non-Hodgkin lymphoma
• The extent of the disease
• Whether the treatment is being given to cure the lymphoma or relieve symptoms (palliate)

Radiation fields

• Radiation treatments are given to different areas of the body when treating Non-Hodgkin lymphoma. The radiation field is the part of the body that receives the radiation. Some of the fields where radiation is given for treating lymphoma are:
• Involved field – most commonly used

• Radiation is given to only 1 or a few lymph node areas known to contain lymphoma and is used for localized, early stage Non-Hodgkin lymphoma. Involved field radiation therapy is also called IFRT.

When radiation is given to a larger area to cover nearby or the next level of lymph node sites, this may be called extended field radiation therapy (EFRT).

• Mantle field

• Radiation is given to the lymph nodes in the neck, chest and underarms

• Upper abdominal field

• Radiation is given to lymph nodes around the heart and aorta (para-aortic area) and possibly the spleen (unless it has been removed)

• Pelvic field

• Radiation is given to lymph nodes in the pelvis and groin
• A large amount of bone marrow is also radiated because the hip bones, which contain the most bone marrow, are in this field

• Inverted (upside down) Y field

• Radiation is given to lymph nodes in the upper abdominal and pelvic fields

Hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation (HSCT), or Bone marrow transplantation (BMT) may also be a treatment option, especially for patients whose non-Hodgkin's lymphoma has recurred (come back). BMT provides the patient with healthy stem cells (very immature cells, found in the marrow, that produce blood cells), the function of which is to replace white blood cells that are damaged or destroyed by treatment with very high doses of chemotherapy and/or radiation therapy. The healthy bone marrow may come from a donor, or it may be "autologous" (marrow that was removed from the patient, stored, and then given back to the person following the high-dose treatment). Autologous transplants are preferred, as the recipient is less likely to reject the cells, the origins of which were the same entity. However, in order for an autologous transplant to be performed, certain physiological conditions must be optimal within the patient. If these conditions are not present, transplanted stem cells can come from other donors. Until the transplanted bone marrow begins to produce enough white blood cells, patients have to be carefully protected from infection due to the virtual elimination of the auto-immune system resulting from the high-intensity treatment. Without the introduction of the stem cells following the high dose treatment, the patient will not survive as the body will be unable to produce infection-fighting white blood cells. Patients usually stay in the hospital for several weeks and will be monitored for transplant rejection and overall health.

Immunotherapy

Biological therapy (also called immunotherapy) is a form of treatment that uses the body's immune system, either directly or indirectly, to fight cancer or to lessen the side effects that can be caused by some cancer treatments. It uses materials made by the body or made in a laboratory to boost, direct, or restore the body's natural defenses against disease. This approach is under close investigation. Biological therapy is sometimes also called biological response modifier therapy.

Measuring response to treatment

After treatment for non-Hodgkin's lymphoma, the response is classified as follows:

• Complete Response (CR). This indicates the disappearance of all detectable disease.
• Partial Response (PR). A reduction in the bulk of disease by at least 50%, but with some remaining disease.
• Stable Disease. Less than a partial remission, but no progression of disease and no new sites of disease.
• Progressive Disease. Growth in bulk of disease by >50%, or the appearance of new sites of disease.

If a complete remission is achieved, the patient is watched closely for any evidence of recurrent disease. Standard guidelines dictate that a patient be monitored for relapse every three months in the first year following a complete remission, every six months in the second year, and finally once annually in the third and later years. Diffuse large b-cell lymphoma is the most common type of lymphoma that is considered curable. Currently, if a patient maintains a complete remission for 3 years, the patient is considered cured. Generally most relapses of diffuse large b-cell lymphoma occur within the first year after a complete remission is obtained. Reoccurences after 3 years are rare but they do occur. The effect of Rituximab on relapse rates for diffuse large b-cell lymphoma is still largely unknown, though initial relapse rates since 2003 have been much lower than expected.

Patients with follicular lymphoma are generally not considered cured. Instead, they are categorized as in ongoing complete remission. Relapses occur steadily over time. Relapse rates are estimated to be 33%, 66%, and 100% for follicular lymphoma's Grades I, II, and III respectively.

Research has indicated that relapse rates can be lowered on patients with follicular lymphoma by giving supplemental radiation therapy, however, it is known that this additional therapy increases the chances of a second malignancy of unknown type later in life.

If the response to treatment falls short of a complete response, more treatment may be administered (using a differentchemotherapy regimen), or watchful waiting may be utilized, depending on the goals of treatment.

Nutrition during treatment

Eating well during cancer treatment means getting enough food energy and protein to help prevent weight loss and regain strength. Good nutrition often helps people feel better and have more energy.

Some people with cancer find it hard to eat a balanced diet because they may lose their appetite. In addition, common side effects of treatment, such as nausea, vomiting, or mouth sores, can make eating difficult. Often, foods may taste or smell different. Also, people being treated for cancer may not feel like eating when they are uncomfortable or tired.

Doctors, nurses, and dietitians can offer advice on how to get enough food energy and protein during cancer treatment. Patients and their families also may want to read the National Cancer Institute (USA) booklet Eating Hints for Cancer Patients, which contains many useful suggestions.

Followup care

People who have had non-Hodgkin's lymphoma should have regular followup examinations after their treatment is over. Followup care is an important part of the overall treatment plan, and people should not hesitate to discuss it with their health care provider. Regular followup care ensures that patients are carefully monitored, any changes in health are discussed, and new or recurrent cancer can be detected and treated as soon as possible. Between followup appointments, people who have had Non Hodgkin's lymphoma should report any health problems as soon as they appear.

References

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