Search

Non-Hodgkin Lymphoma

Lymphoma comprises more than 67 subtypes of two related cancers that affect the lymphatic system, Hodgkin lymphoma (formerly referred to as Hodgkin's lymphoma) and non-Hodgkin lymphoma (NHL) (formerly referred to as non-Hodgkin's lymphoma). There are six types of Hodgkin lymphoma and at least 61 types of non-Hodgkin lymphoma. Non-Hodgkin lymphomas are different from Hodgkin lymphomas in the way they develop, spread and are treated. Lymphoma is the most common blood cancer and the third most common cancer among children.

Attend an Education Program
Contact the Helpline
Join the Support Network
Order Free Publications
Focus On FL

Overview

Non-Hodgkin lymphoma is the most common cancer of the lymphatic system. Since the early 1970's, incidence rates for NHL have nearly doubled. Over the 25-year period between 1973 and 1998, new cases of NHL seen each year escalated almost 83 percent, among the highest increases of any cancer. The overall five-year survival rate is only 63 percent. Of the nearly 500,000 Americans with lymphoma, 332,000 have this form. In 2009, it is estimated that 65,980 new cases of NHL will be diagnosed and 19,500 Americans will die from the disease. NHL is not a single disease, but rather a group of several closely related cancers that affect the lymphatic system, which is part of the immune system.

Non-Hodgkin lymphoma is broadly divided into two major groups: B-cell lymphomas (which develop from abnormal B-lymphocytes, which is most common), and T-cell lymphomas (which develop from abnormal T-lymphocytes). Lymphocytes are a type of white blood cell that helps the body fight infections. B-cells develop into plasma cells that produce antibodies to fight infections, while T-cells attack foreign invaders (bacteria, viruses, etc.) directly.

Development

Non-Hodgkin lymphoma can start in the lymph nodes, in a specialized lymphatic organ such as the spleen, or in lymph tissue found in organs such as the stomach or intestines. Since lymphocytes (white blood cells) can circulate to all parts of the body through the lymphatic vessels and bloodstream, abnormal lymphocytes can spread to any part of the body. While some NHLs are localized to one area, most are present in other parts of the body by the time the diagnosis is confirmed.

Signs and Symptoms

While most people who have these complaints will not have NHL, anyone with persistent symptoms should be seen by a doctor to make sure that lymphoma is not present: chills, swelling of the lymph nodes (which are often but not always painless), fever, night sweats, unexplained weight loss, lack of energy, and itching.

Risk Factors

The causes of non-Hodgkin lymphoma remain unknown, but immune system impairment and exposure to environmental carcinogens, pesticides, herbicides, viruses, and bacteria may play a role. There may be a higher risk for getting NHL in individuals:

  • With a family history of NHL (though no hereditary pattern has been well established)
  • Affected with autoimmune disease
  • Who have received an organ transplant
  • Exposed to chemicals such as pesticides, fertilizers or solvents
  • Infected with viruses such as Epstein-Barr, human T-lymphotropic virus type 1, HIV, hepatitis C or certain bacteria, such as H-pylori

Treatment

Many people treated for NHL will receive some form of chemotherapy, radiation therapy, biologic therapy, or a combination of these. Bone marrow or stem cell transplantation may sometimes be used. Surgery may be used under special circumstances, but primarily to obtain a biopsy for diagnostic purposes. 

While many effective treatment options exist, indolent (slow-growing) forms of NHL usually recur, and some people go in and out of remission for years. In certain patients with indolent disease, treatment may not be necessary until there are signs of progression. Treatment that worked initially may be ineffective the next time, making it necessary to always keep abreast of the latest information on new or experimental treatment options.

Current Research

The Lymphoma Research Foundation funds some of the most innovative research to find a cure for NHL.

NHL Resources

The Lymphoma Research Foundation has developed a number of resources, in a variety of formats, to provide relevant information to those diagnosed with NHL as well as their caregivers and loved ones.

For more information, call 1-800-500-9976, e-mail helpline@lymphoma.org, or continue to visit www.lymphoma.org.

Types of NHL & Disease-Specific Resources

AIDS-Related Lymphomas
Anaplastic Large-Cell Lymphoma
Angioimmunoblastic Lymphoma
Blastic NK-Cell Lymphoma
Burkitt’s Lymphoma, Burkitt-like Lymphoma (Small Non-Cleaved Cell Lymphoma)
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Cutaneous T-Cell Lymphoma
Diffuse Large B-Cell Lymphoma
Enteropathy-Type T-Cell Lymphoma
Follicular Lymphoma
Hepatosplenic Gamma-Delta T-Cell Lymphoma
Lymphoblastic Lymphoma
Mantle Cell Lymphoma
Marginal Zone Lymphoma
Nasal T-Cell Lymphoma
Pediatric Lymphoma
Peripheral T-Cell Lymphomas
Primary Central Nervous System Lymphoma
T-Cell Leukemias
Transformed Lymphomas
Treatment-Related T-Cell Lymphomas
Waldenstrom's Macroglobulinemia

AIDS-Related Lymphomas
Lymphomas occurring in HIV-positive patients are usually aggressive. It is estimated that as many as ten percent of people who are HIV-positive will ultimately develop lymphoma. Although both Hodgkin and non-Hodgkin lymphomas may occur in AIDS patients, non-Hodgkin lymphomas are more common and include diffuse large B-cell, Burkitt’s/Burkitt-like and primary central nervous system lymphoma.

Anaplastic Large-Cell Lymphoma
Anaplastic large-cell lymphoma (ALCL) is a rare type of aggressive T-cell lymphoma comprising about 3 percent of all lymphomas in adults and between 10 percent and 30 percent of all lymphomas in children. It can present either systemically (meaning in organs throughout the body) or cutaneously (on the surface of the skin). Systemic anaplastic large-cell lymphoma may respond well to chemotherapy treatment and is potentially curable. When ALCL is confined to the skin, it follows a less aggressive course and is associated with a rare condition called lymphomatoid papulosis (LyP), which, though not classified as a lymphoma, is often a precursor to development of cutaneous anaplastic large-cell lymphoma. Patients with systemic ALCL are divided into two groups, depending on the expression of a protein called anaplastic lymphoma kinase (ALK). The prognosis for ALCL depends on whether a patient is ALK positive (expresses the protein) or ALK negative (does not express the protein). ALK positive disease responds well to chemotherapy, putting most patients in long-term remission or cure. A majority of ALK negative patients will relapse within five years and are treated more aggressively, often with transplant.

Angioimmunoblastic Lymphoma
Angioimmunoblastic lymphoma (AILD) is a fast-growing T-cell lymphoma that accounts for between one percent and two percent of all cases of NHL in the United States. Symptoms include high fever, night sweats, skin rash and some types of autoimmune disorders, such as autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP), in which the body does not recognize its own cells. As a result, the body makes antibodies against and destroys its own cells or tissues, such as platelets (ITP) and red blood cells (AIHA). Angioimmunoblastic lymphoma may be treated first with steroids, although it often progresses and requires chemotherapy and other medications. In advanced cases, transplantation may be used.

Blastic NK-Cell Lymphoma
Blastic NK-cell lymphoma is a very rare T-cell lymphoma, affecting only a few people (usually adults) each year. This lymphoma is very fast growing, is difficult to treat and can arise anywhere in the body. Since this disease is so rare, patients should consult with their medical team to find promising therapies or clinical trials.

Burkitt Lymphoma, Burkitt-like Lymphoma (Small Non-Cleaved Cell Lymphoma)
Burkitt lymphoma is an aggressive B-cell form of NHL that occurs most often in children and young adults. There are three main types of Burkitt’s lymphoma: sporadic, endemic and immunodeficiency-related disease. While sporadic Burkitt’s lymphoma occurs throughout most of the world, endemic Burkitt's lymphoma is found mostly in Africa and is often associated with the Epstein-Barr virus (EBV). Immunodeficiency-related Burkitt's lymphoma is diagnosed most often in people infected with HIV/AIDS. The disease may affect the jaw, central nervous system, bone marrow, bowel, kidneys, ovaries or other organs. Burkitt's lymphoma has a specific chromosomal abnormality called the t(8;14) translocation and behaves aggressively. Burkitt's lymphoma is potentially curable.

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
According to the American Cancer Society, approximately 15,000 new cases of CLL and 3,600 new cases of SLL are diagnosed annually. This form of cancer is usually diagnosed in older adults over the age of 50—more than half of the people with CLL are over age 70. Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are considered B-cell malignancies and are essentially the same disease with slightly different manifestations. The same kind of cell, known as a lymphocyte, is involved in both CLL and SLL. The only difference between the two diseases is where the cancer primarily occurs. When the cancer cells are located mostly in the lymph nodes, the disease is called SLL. When most of the cancer cells are located in the bloodstream and the bone marrow, the disease is referred to as CLL, although the lymph nodes and spleen are often involved as well. Thinking of CLL/SLL as a lymphoma and not a form of leukemia is important because CLL has a clinical course and treatment regimen that is similar to other indolent lymphomas. Chronic lymphocytic leukemia tends to be a slow-growing cancer. However, over time, it can progress to a more aggressive type of lymphoma. The staging system for CLL is different from the staging system applied to other NHLs.

Cutaneous T-Cell Lymphoma
Cutaneous T-cell lymphomas (CTCL) arise in the skin and account for approximately two percent to three percent of all NHL cases. The age of presentation is usually between 55 and 60 years. The most common form of CTCL is mycosis fungoides, which is often indolent and appears as reddish patches, plaques or scales on the skin. An advanced, or variant, form of mycosis fungoides is called Sézary syndrome, which is often characterized by redness and scaling of the skin, enlarged lymph nodes and malignant T-cells circulating in the blood. Depending on the symptoms or stage of disease, treatments are directed at the skin (e.g., ultraviolet light, topical steroids, topical chemotherapies, topical retinoids and electron beam radiation therapy) or the entire body (e.g., oral retinoids, photopheresis, fusion proteins, interferon and systemic chemotherapy).

Diffuse Large B-Cell Lymphoma
Diffuse large B-cell lymphoma (DLBCL) is the most common form of NHL, accounting for up to one-third of newly diagnosed cases. Although most frequently seen in adults—the median age at diagnosis is 57—the disease may also be seen in young people. The disease is an aggressive, or fast-growing, lymphoma and can arise in the lymph nodes or outside of the lymphatic system. It may be localized or generalized (spread throughout the body). Despite being an aggressive lymphoma, DLBCL is potentially curable. The first sign of DLBCL is usually rapid swelling in the neck, armpit or groin caused by enlarged lymph nodes. Other symptoms include night sweats, chills, unexplained fevers and weight loss.

Enteropathy-Type T-Cell Lymphoma
Enteropathy-type T-cell lymphoma is an extremely rare subtype of T-cell lymphoma that appears in the intestines and is strongly associated with celiac disease. As with other rare cancers, patients should discuss treatment options with their medical team.

Follicular Lymphoma
Follicular lymphoma (FL) is the most common indolent (slow- growing)form of NHL, accounting for approximately 12 percent of all B-cell NHLs, and typically occurs in middle-aged and older adults, but it can affect younger people in their 30s and 40s. Follicular lymphoma is typically slow-growing (indolent) and arises from B-lymphocytes, making it one of the B-cell lymphomas. Follicular lymphoma usually appears in lymph nodes throughout the body. They arise in the germinal center or follicle of the lymph node. Often, the first sign of follicular lymphoma is a painless swelling in the neck, armpit or groin caused by enlarged lymph nodes. Because follicular lymphoma is a common indolent lymphoma, it is often used as a model for the treatment of other slow-growing lymphomas. Follicular lymphoma may eventually transform into a more aggressive form of the disease, often referred to as histologic transformation. As with most indolent lymphomas, follicular lymphoma may present itself in many parts of the body, including the bone marrow.

Hepatosplenic Gamma-Delta T-Cell Lymphoma
Hepatosplenic gamma-delta T-cell lymphoma is an extremely rare and aggressive disease that starts in the liver or spleen. This lymphoma may occur in people with Crohn’s disease whose immune system is suppressed. As with other rare cancers, patients should discuss treatment options with their medical team.

Lymphoblastic Lymphoma
Lymphoblastic lymphoma can appear in both B-cells and T-cells, but is much more common in T-cells, comprising 80 percent of all lymphoblastic lymphomas. This lymphoma is most often diagnosed in children. With intensive chemotherapy, the complete remission rate can be very high. The disease is often treated similarly to acute lymphoblastic leukemia.

Mantle Cell Lymphoma
Mantle cell lymphoma is a B-cell lymphoma that affects approximately six percent of all NHL patients. Mantle cell lymphoma usually affects men over 50. Frequently, patients with mantle cell lymphoma have many lymph nodes, one or more organs and bone marrow involved. The gastrointestinal tract is a very common extra-nodal site of involvement. Mantle cell lymphoma may initially follow an indolent (slow-growing) course, but may transform early into an aggressive disease and is, therefore, often treated as an aggressive lymphoma. In general, it is currently incurable with standard approved therapies.

Marginal Zone Lymphoma
Marginal zone B-cell lymphomas, a group of indolent lymphomas whose cells come from B-lymphocytes normally found in the marginal zone of the secondary lymphoid follicles in the spleen and lymph nodes, accounts for approximately seven percent of all NHLs. The median age for diagnosis of this type of lymphoma is 65. Marginal zone lymphomas encompass three basic types: (1) extranodal or mucosa-associated lymphoid tissue (MALT), occurring outside the lymph nodes, (2) nodal, occurring within the lymph nodes, and (3) splenic, occurring mostly in the spleen and blood. Skin-associated lymphoid-tissue-related B-cell lymphoma (SALT) is also considered a form of MALT lymphoma. Marginal zone and MALT lymphomas vary from other types of B-cell NHLs in a number of ways: (1) their natural history is different; (2) many people who develop MALT lymphoma have a history of inflammation or autoimmune disorders; (3) chronic inflammation is associated with Helicobacter pylori (H. pylori), a microbial pathogen linked to chronic gastritis; and, (4) sometimes, MALT lymphomas can be treated with antibiotics. Different infections have also been implicated in other forms of MALT lymphoma. Hepatitis C has been associated with splenic marginal zone lymphoma. Nodal marginal zone B-cell lymphomas are uncommon and are sometimes called monocytoid B-cell lymphomas.

Nasal T-Cell Lymphoma
Although this fast-growing lymphoma is very rare in the United States, it is relatively common in Asia and parts of Latin America, leading researchers to suspect that some ethnic groups may be more prone to this cancer, which affects both children and adults. This type of lymphoma is associated with the Epstein-Barr virus. As with other rare cancers, patients should consult with their medical team for treatment options and the availability of clinical trials.

Pediatric Lymphoma
Childhood NHL comprises about five percent of all NHL cases diagnosed in the United States. The most common types are lymphoblastic lymphoma, Burkitt’s lymphoma, diffuse large B-cell lymphoma and anaplastic large-cell lymphoma. Lymphoblastic lymphoma is closely related to childhood acute lymphoblastic leukemia. The number of children with NHL continues to increase.

Peripheral T-Cell Lymphomas
Peripheral T-cell lymphomas (PTCL) refer to a large number of different T-cell lymphomas that together comprise between 10 percent and 15 percent of all NHL cases and can occur anytime during adulthood. The term "peripheral T-cell lymphoma" is based on the fact that these tumors are composed of T-cells (not B-cells) and that the cells are mature. Most peripheral T-cell lymphomas are aggressive; with the exception of mycosis fungoides. Some varieties of peripheral T-cell lymphoma are quite rare in the United States but can more commonly be found in Asia, notably Japan, where an infection with a virus called HTLV-1 is prevalent. Its presence makes it more likely for an individual to develop a specific type of peripheral T-cell lymphoma. It has also been found in individuals coming from Caribbean countries.

Primary Central Nervous System Lymphoma
Primary central nervous system lymphoma (PCNSL) is a type of cancer that is limited to the brain or spinal cord but may also be found in tissues around the eye. An increasing occurrence of this disease has been seen in patients with AIDS and others whose immune system has been compromised. Median age of diagnosis for patients with PCNSL is 55 years for patients with a normal immune system and 31 years for AIDS patients. Although in the past the outlook for patients with this cancer has been poor, today, the survival rate has greatly improved.

T-Cell Leukemias
T-cell leukemias are also derived from T-cells and can act like T-cell lymphoma. These cancers include T-cell promyelocytic leukemia, T-cell granular lymphocytic leukemia, aggressive NK-cell leukemia and adult T-cell lymphoma/leukemia.

Transformed Lymphomas
Although indolent B-cell lymphomas, such as follicular lymphomas, are most commonly associated with transforming to aggressive disease, slow-growing T-cell lymphomas can also progress to aggressive disease.

Treatment-Related T-Cell Lymphomas
Treatment-related T-cell lymphomas may appear after solid organ or bone marrow transplantation. The immune system suppression that is required for transplant patients can put them at risk for developing post-transplant lymphoproliferative disorders, certain unusual forms of peripheral T-cell lymphoma and other types of NHL. Treatment-related T-cell lymphomas may require therapy that differs from the standard treatments normally used to treat these conditions.

Waldenstrom Macroglobulinemia
Waldenstrom macroglobulinemia (also known as lymphoplasmacytic lymphoma or immunocytoma) is a rare B-cell lymphoma that occurs in less than two percent of people with NHL. There are about 1,500 new cases of Waldenstrom each year. The disease usually affects older adults and is primarily found in the bone marrow and spleen, although lymph nodes may sometimes be involved. Waldenstrom is characterized by a high level of a protein called immunoglobulin M (IgM) in the blood. These high levels of IgM can cause a thickening of the blood, resulting in symptoms such as nosebleeds, headaches, dizziness and blurring or loss of vision.