What is non-Hodgkin lymphoma?

Risk factors: Some known and potential risk factors for non-Hodgkin
lymphoma include age (over forty years); gender (more common in men); a
compromised immune system (such as from immunosuppressant treatments or acquired
immunodeficiency syndrome, AIDS); autoimmune or chronic inflammatory conditions,
such as rheumatoid arthritis and Sjögren
syndrome; chronic infection, such as with Epstein-Barr
virus (increases risk of Burkitt
lymphoma),
Helicobacter pylori
,
and hepatitis C
virus; radiation exposure; and chemical exposure (such as to
certain solvents, pesticides, herbicides and fertilizers).

Despite the list of known and suspected risk factors for non-Hodgkin lymphoma, most people diagnosed have no known risk factors, and many who have risk factors never develop the disease.

Etiology and the disease process: For most patients, the exact cause
of non-Hodgkin lymphoma is unknown. One suspected cause is the activation of
certain abnormal genes that allow uncontrollable lymphocyte division and growth.
This uncontrolled growth causes lymph nodes and other lymphatic tissues to swell.
Because lymphatic tissue is in various locations throughout the body, non-Hodgkin
lymphoma can start almost anywhere and tends to be widespread, although
slower-growing types may be confined to one place. Typically, non-Hodgkin lymphoma
begins in the lymph nodes and spreads to other parts of the lymphatic system.
Occasionally, non-Hodgkin lymphoma also invades organs outside the lymphatic
system, including the stomach, brain, and lungs.

Incidence: Non-Hodgkin lymphoma is the fifth most common type of
cancer among adults and the sixth leading cause of cancer deaths in the United
States. According to the National Cancer Institute, in 2014, an estimated 70,800
non-Hodgkin lymphoma cases were diagnosed and 18,990 deaths were attributed to
non-Hodgkin lymphoma.

Non-Hodgkin lymphoma occurs in all age groups, but the risk of developing the disease increases with age (95 percent of cases occur in adults age forty and older). Some subtypes are more common in certain age groups. In children, non-Hodgkin lymphoma is most commonly diagnosed between the ages of seven and eleven, and some types of non-Hodgkin lymphoma are among the most common childhood cancers.

Symptoms: Symptoms vary depending on the area of the body in which the tumor originated and the areas to which the cancer has spread. Swollen, painless lymph nodes in the neck, underarms, stomach, or groin are commonly the only sign of non-Hodgkin lymphoma in early stages.

Generalized symptoms include fever, unexplained weight loss, fatigue, excessive sweating, night sweats, chills, easy bruising, itchiness, and unusual infections.

Tumors in the stomach can cause pain and swelling, which can lead to loss of appetite, constipation, nausea, and vomiting. Tumors in the thymus or chest lymph nodes can cause coughing and shortness of breath. Lymphoma of the brain can cause headaches, personality changes, and seizures.

Screening and diagnosis: Many tests are used to diagnose non-Hodgkin lymphoma and assess the spread of the disease. Diagnosis begins with a medical history and physical examination, which commonly focuses on the lymph nodes, liver, and spleen. Blood and urine tests may be performed to help rule out infections and other diseases that cause swollen nodes.

An excisional biopsy is the best way to definitively diagnose lymphoma and
determine the subtype.

Lymph node biopsy from the neck, armpits, or groin is most common. Bone marrow biopsy may be performed to establish whether the disease has spread.

Imaging tests such as X-rays, magnetic resonance imaging, and computed
tomography scanning may be used to detect the presence of non-Hodgkin lymphoma,
determine the size of tumors, and determine the extent to which the cancer has
spread.

Staging helps to determine treatment. A system commonly used to stage
non-Hodgkin lymphoma is a modified Ann Arbor staging system. This system
classifies lymphoma into four stages:

• Stage I: Lymphoma is limited to a single region, usually one lymph node or one lymph node region in the body.





• Stage II: Lymphoma involves two or more lymph node regions on the same
  side of the diaphragm.





• Stage III: Lymphoma has spread to lymph node regions on both sides of the
  diaphragm.





• Stage IV: Widespread disease has affected one or more nonlymphatic
  organs.

A lettering system is commonly used in combination with the stage to indicate
the presence of symptoms. An “E” indicates involvement of organs outside the lymph
system; a “B” indicates the presence of weight loss, night sweats, or unexplained
fever; an “A” indicates the absence of symptoms; and an "S" indicates the
involvement of the spleen.

Treatment and therapy: Treatment of non-Hodgkin lymphoma depends on the type and stage of the disease, symptoms, and the patient’s age and overall medical condition. Three main treatments are used: chemotherapy, radiation therapy (RT), and immunotherapy (also called biological therapy). Surgery is rarely used to treat the disease but may be used to relieve problems caused by non-Hodgkin lymphoma, such as bowel obstruction and spinal cord compression.

Chemotherapy is the primary treatment for non-Hodgkin lymphoma. It may be used
alone or in combination with other treatments. Intermediate- and high-grade
lymphomas and advanced low-grade lymphomas are commonly treated with multiple
agents; single-drug therapy may be used for early-stage, low-grade disease. The
exact medications, routes, doses, and duration of treatment depend on the stage
and type of lymphoma. A common chemotherapy regimen for the initial treatment of
non-Hodgkin lymphoma includes cyclophosphamide, doxorubicin, vincristine, and
prednisone. Patients are usually treated on an outpatient basis unless problems
arise.

Radiation therapy is used to kill or shrink cancer cells. In some cases of Stage I and II non-Hodgkin lymphoma, curative treatment with radiation therapy is possible. Sometimes, radiation therapy is used with chemotherapy to treat intermediate-grade tumors or tumors in specific sites, such as the brain. However, it is typically ineffective against more advanced lymphomas. Radiation therapy may also be used to ease symptoms.

Immunotherapy is an evolving treatment in which substances naturally made by
the immune system are used to kill lymphoma cells or slow their growth.
Investigational immunotherapies for non-Hodgkin lymphoma include monoclonal
antibodies and interferons. Rituximab is a monoclonal antibody approved by the US Food and Drug
Administration for the treatment of B-cell non-Hodgkin lymphoma. It is commonly
used in combination with chemotherapy. Some forms of radioimmunotherapy, in which
monoclonal antibodies are attached to radioactive substances, are also used to
treat non-Hodgkin lymphoma. Examples include ibritumomab and tositumomab. Because
of their life-threatening side effects, these drugs are used only after other
treatments have failed.

If non-Hodgkin lymphoma recurs, treatment with high-dose chemotherapy, total-body or total-lymph node irradiation, or bone marrow or stem cell transplantation may be necessary.

Prognosis, prevention, and outcomes: The one-year relative survival
rate for non-Hodgkin lymphoma is 81 percent; five-year, 63 percent; and ten-year,
49 percent. Rates vary depending on the person, type of lymphoma, and stage of
disease. As with most other cancers, the earlier the diagnosis, the greater the
chances for successful treatment. However, 70 percent to 80 percent of patients
with aggressive lymphomas achieve complete remission with treatment. Typically,
the type of tissue involved is a better prognostic predictor than cancer
stage.

The International Prognostic Index (IPI) is used to help predict lymphoma growth and patient response to treatment. Based on patient age, cancer stage and spread, patient function, and lactate dehydrogenase levels, the IPI is mainly used in patients with aggressive lymphomas.

Low-grade non-Hodgkin lymphomas tend to be advanced when diagnosed. Although
they usually respond well to treatment, they may also recur. High-grade
non-Hodgkin lymphomas sometimes require intensive chemotherapy. These lymphomas
are often curable (some have 60 to 80 percent cure rates). However, if the cancer
does not respond to chemotherapy, the disease can cause death.

Because most people who have non-Hodgkin lymphoma have no known risk factors
and the cause of the cancer is unknown, prevention is elusive.

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