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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

Chemotherapy

Chemotherapy plays a role in the treatment of nearly all lymphoma patients and has achieved remarkable results, even in late stages. It uses drugs to kill cancer cells. Such drugs are called cytotoxic drugs. Chemotherapy is referred to as bodywide or systemic therapy because the drugs travel throughout the bloodstream to the entire body.

Studies indicate that chemotherapy as sole treatment is adequate for most children and young adults in early and perhaps in many advanced stages. (Radiation has been commonly used for these patients but carries particular dangers for children.)

Chemotherapy Administration

A chemotherapy cycle is usually 21 - 28 days. Patients take the drugs for a few days, then have a period of rest. The drugs may be taken by mouth or given by injection. Chemotherapy is injected into the spinal fluid if the cancer has spread to the brain. This is called intrathecal chemotherapy. Intrathecal chemotherapy is also used as a preventive measure in patients at high risk for central nervous system involvement. Chemotherapy may be administered at a medical center or in a doctor's office. Some patients receiving chemotherapy need to remain in the hospital for several days so the effects of the drug can be monitored. Patients with lymphoblastic lymphoma may need long-term maintenance chemotherapy. Such therapy does not seem to benefit patients with small-noncleaved-cell and large-cell lymphomas.

Effective Regimens and Drugs

CHOP. The current standard chemotherapy regimen for NHL is CHOP. CHOP is a combination of cyclophosphamide, doxorubicin hydrochloride (Adriamycin), vincristine (Oncovin), and prednisone. It is proving to be particularly effective for many stages of lymphoma when used in combination with rituximab (Rituxan), a monoclonal antibody. Some studies of this combination in low-grade lymphomas have reported response rates of 70 - 100%. CHOP alone is still preferred for HIV patients, who tend to have a toxic response to rituximab.

CVP. This stands for cyclophosphamide, vincristine, and prednisone. It may be used with CHOP in certain cases.

Fludarabine and Nucleoside Analogues. Fludarabine (Fludara) is a type of drug called a nucleoside analogue. It is one of the most active drugs for treating low-grade lymphomas and may be effective for other NHLs, including mantle cell lymphomas. Promising regimens containing fludarabine are under investigation. For example, FND (fludarabine, mitoxantrone, and dexamethasone) may be helpful in combination with rituximab for certain patients, including those with indolent NHL. Other nucleoside analogues include gemcitabine and cladribine. Toxicities and infection rates from high dose nucleoside analogues have been high. Fludarabine also has been associated with a risk for leukemia.

Bendamustine. This potent drug has shown to be effective for indolent NHLs and possibly aggressive lymphomas. One study suggested that a single dose of low-dose etoposide, taken by mouth, may be beneficial for elderly patients.

Other Drugs

Antibiotics. Antibiotics, such as doxycycline, may cure or put into complete remission about half of mucosa-associated lymphoid tissue (MALT) lymphoma cases. MALT lymphoma is a type of lymphoma that sometimes affects the eyes. It is associated with the bacterium Helicobacter pylori ( H. pylori ), which also causes stomach ulcers. Doctors are finding that antibiotics are a good alternative to chemotherapy or radiation for patients with this type of lymphoma. Patients most likely to respond positively to antibiotics are those with MALT lymphoma in its early stages.

Vorinostat . Vorinostat (Zolinza) was approved in 2006 for treatment of cutaneous T-cell lymphoma (CTCL), a rare form of NHL.

Supportive Drugs

Granulocyte Colony-Stimulating Factor. Granulocyte colony-stimulating factor or G-CSF (lenograstim, filgrastim, sargramostim, nartograstim) regulates blood-cell growth. It is used to allow higher doses of chemotherapy. Doctors hope it might reduce infections and allow standard chemotherapy treatments and in elderly people, who otherwise could not withstand toxicities. Studies suggest it speeds up recovery after treatment but it is unclear if it reduces the rate of infection. Toxicities and infections are still common, even with the use of G-CSF.

Side Effects and Complications

Side effects and complications of any chemotherapeutic regimen are common. They are more severe with higher doses. Side effects may increase over the course of treatment.

Common Side Effects . Common side effects include:

• Nausea and vomiting -- Drugs known as serotonin antagonists, such as ondansetron (Zofran) or granisteron (Kyril), can relieve these side effects in nearly all patients given moderate drugs and most patients who take more powerful drugs.
• Diarrhea
• Hair loss
• Weight loss
• Depression

These side effects are nearly always temporary. Most patients are able to continue with normal activities for all but perhaps a few days a month.

Serious Side Effects. Serious side effects can also occur and may vary depending on the specific drugs used. They include the following:

• Neutropenia is a severe drop in white blood cells. Neutropenia increases the chance for infection from suppression of the immune system. White blood cell count may be improved with the addition of a drug called granulocyte colony-stimulating factor (filgrastim, pegfilgrastim, and lenograstim). There is no evidence that these drugs have any effect on survival or cancer recurrence.
• Anemia is a lack of red blood cells. Erythropoietin stimulates red blood cell production and can help reduce or prevent this side effect. It is available as epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp). Aranesp persists longer in the blood than epoetin alfa and requires fewer injections.
• Liver and kidney damage
• Abnormal blood clotting ( thrombocytopenia )
• Allergic reaction

Long-Term Complications.

• Fatigue and Somatic Symptoms. Chemotherapy has been associated with long-term somatic symptoms, which are general conditions, such as fatigue and aches and pains that have no apparent physical basis. Fatigue is especially common after chemotherapy and can even last for years.
• The most serious long-term complications from chemotherapy are secondary cancers, particularly in people over age 40.
• Infertility is also a danger, particularly with the use of cyclophosphamide.
• Some patients report osteoporosis and damage in bone cells, possibly related to corticosteroid treatments.
• Regimens containing certain drugs, particularly doxorubicin or mitoxantrone, increase the risk for future heart failure.

In general, these serious late side effects are dependent on the cumulative drug dose and rate of administration. There is a 1 - 5% mortality rate from complications of chemotherapy and certain people may be at greater risk. A 2001 study suggested that the risk was highest in those who had low performance scores (are more debilitated than others) or have tests that show low levels of white blood cells.

Combinations of Chemotherapy and Radiation (Combined Modality)

Doctors are particularly concerned about the effects of combinations of chemotherapy with radiation, especially leukemia and heart problems. Interestingly, in one study on patients with intermediate- and high-grade NHL, those on chemotherapy alone had more toxic effects than those on combined modality, most likely because it employed fewer cycles of chemotherapy. Better radiation techniques are also reducing the risks of combined modality treatments.

• 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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