Non-Hodgkin lymphoma

ALSO KNOWN AS: Non-Hodgkin’s lymphoma, NHL

RELATED CONDITIONS: Autoimmune disorders

DEFINITION: Non-Hodgkin lymphoma describes a group of more than twenty different cancers originating in the lymphatic system, a part of the immune system. This system, which fights disease and infection, consists of the body's lymph nodes, spleen, bone marrow, and other organs. Non-Hodgkin lymphoma develops in two types of white blood cells (lymphocytes)—B cells and T cells. Most lymphomas (90 percent) start in B cells.

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 a common cancer among adults, with more than half of cases occurring in those sixty-five or older at diagnosis. Non-Hodgkin lymphoma occurs in all age groups, but the risk of developing the disease increases with age. Some subtypes are more common in certain age groups. In children, non-Hodgkin lymphoma is most common 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 where the tumor originated and the areas in which the cancer has spread. Swollen, painless lymph nodes in the neck, underarms, stomach, or groin are commonly the only signs of non-Hodgkin lymphoma in the 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, leading 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 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 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. The Lugano classification system, a modified Ann Arbor staging system, is commonly used to stage non-Hodgkin lymphoma. 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 with the stage to indicate the presence of symptoms. An “E” indicates the 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 include chemotherapy, radiation therapy (RT), and immunotherapy (biological therapy). Surgery is rarely used to treat the disease but may be used to relieve associated problems, such as bowel obstruction and spinal cord compression.

Chemotherapy is the primary treatment for non-Hodgkin lymphoma. It may be used alone or with other therapies. Intermediate, high-grade, 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 kills or shrinks 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 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. Other forms of monoclonal antibody treatments include brentuximab vedotin (Adcetris), moxetumomab pasudotox, pembrolizumab (Keytruda), and nivolumab (Opdivo). 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 overall five-year survival rate for individuals with non-Hodgkin lymphoma is over 70 percent. The ten-year survival rate is 60 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. The tissue type involved is usually a better prognostic predictor than the 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 at diagnosis. 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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