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What Is Non-Hodgkin Lymphoma? An Overview

Posted on July 19, 2021
Medically reviewed by
Mark Levin, M.D.
Article written by
Kristopher Bunting, M.D.

Non-Hodgkin lymphoma (NHL), a blood cancer, is one of two main types of lymphoma. The other is Hodgkin lymphoma (also called Hodgkin disease), and both types have multiple subtypes. Lymphoma is related to other blood cancers, including leukemia, myeloma, and myeloproliferative neoplasms (MPNs). Each of these conditions arises from different types of blood cells and appears in different parts of the body.

Lymphoma forms from abnormal lymphocytes — a type of white blood cell — and occurs in the lymphatic system. The lymphatic system is part of both the immune system and the circulatory system. It includes multiple organs, including bone marrow, lymph channels, lymph nodes, the spleen, the thymus, the tonsils, and tissue in the digestive tract. The purpose of the lymphatic system is to drain excess fluid and remove waste and bacteria from the body.

Non-Hodgkin lymphomas are very treatable. Survival rates vary according to the subtype of NHL, but overall, NHL has a good survival rate with treatment.

What Causes Non-Hodgkin Lymphoma?

Lymphoma, like other cancers, is caused by genetic mutations in cells that become cancer cells. Some risk factors for developing NHL include age, sex, ethnicity, certain inherited genes, autoimmune disease, and having a weakened immune system. Other risk factors, called acquired risk factors, are potentially avoidable. These risk factors include:

  • Radiation exposure
  • Chemical exposure (including certain chemotherapy drugs)
  • Infections such as HIV and Epstein-Barr virus

Learn more about what causes lymphoma.

Signs and Symptoms of Non-Hodgkin Lymphoma

Signs and symptoms are different indicators of a condition. Symptoms are what a person experiences, such as a headache or fatigue. Signs are observable or measurable by a doctor, such as a fever or high blood pressure. Non-Hodgkin and Hodgkin lymphomas share many signs and symptoms. Some of the symptoms — fever, night sweats, and unexplained weight loss — are called B symptoms. B symptoms are systemic symptoms that affect the whole body.

Other common signs and symptoms include:

  • Swollen lymph nodes, especially in the neck, armpits, and groin
  • Fatigue
  • Coughing, chest pain, or shortness of breath, caused by enlarged lymph nodes in the chest
  • Swollen abdomen, due to an accumulation of fluid in the abdomen or an enlarged liver or spleen
  • Frequent infections
  • Central nervous system symptoms such as headaches, changes in personality, difficulty thinking, and seizures
  • Nausea and vomiting
  • Loss of appetite
  • Abdominal pain

Note that most signs and symptoms of lymphoma can also occur with other medical conditions, including other types of cancer, so talk to your doctor if you have concerns.

Read more about signs and symptoms of lymphoma.

Diagnosis and Staging of Non-Hodgkin Lymphoma

Diagnosis of both non-Hodgkin and Hodgkin lymphoma begins with a thorough medical history and physical exam to identify what signs, symptoms, and risk factors you may have. Additional tests used to diagnose and stage NHL include biopsies of tumors and bone marrow, imaging tests, and blood tests. A pregnancy test is also very important in women of reproductive age. Hepatitis testing is recommended before starting therapy.

Staging of non-Hodgkin lymphoma involves classifying the spread of the disease — which organs are affected — in order to determine the appropriate treatments and a disease prognosis.

Physical Exam

A thorough physical exam for lymphoma includes careful palpation (feeling by hand) of the neck, armpits, and groin for swollen lymph nodes. Your doctor may also feel your abdomen to check for enlargement of the spleen.

Biopsy

When performing a biopsy, a doctor takes a sample of a tumor or mass to analyze it for abnormalities. A biopsy can be useful to diagnose cancer and to identify what kind it is. Surgical removal of an entire lymph node or a significant portion of it is the best way to clearly identify and diagnose lymphoma and its subtype.

Imaging

Imaging tests such as X-rays, CT scans, positron emission tomography (PET) scans, and MRI can help doctors find tumors throughout the body.

Blood Tests

The most important blood test for non-Hodgkin lymphoma is a complete blood count (CBC). CBC testing measures the amounts of red blood cells, hemoglobin, white blood cells, and platelets in a blood sample. Further analysis, called differential analysis, looks at the different types of white blood cells in a blood sample and whether or not they appear abnormal.

Standard blood tests for liver and kidney function, as well as tests for HIV and hepatitis B and C, are also needed to help determine which treatments are most appropriate.

Learn more about diagnosing lymphoma.

Stages of Non-Hodgkin Lymphoma

After diagnosis, your doctor will stage your cancer to describe the extent of the disease. Different types of cancer use different systems for staging, but cancer stages are usually described as stage 1 through 4 (sometimes using Roman numerals) with subclassifications. Non-Hodgkin lymphoma is staged using the Lugano classification system. In this system, stages are based on whether the lymphoma is localized or widespread, especially if the lymphoma has spread from one side of the diaphragm to the other. Stages are defined further by the size, or bulk, of the tumor, and whether or not lymphoma has spread beyond the lymphatic system.

Stages 1 and 2 are limited to one side of the diaphragm, involving lymph nodes or one organ outside the lymphatic system. Stages 3 and 4 are characterized by advanced lymphoma that has spread to both sides of the diaphragm and that may include organs outside of the lymphatic system.

Staging Small Lymphocytic Lymphoma

A type of NHL called small lymphocytic lymphoma (SLL) involves the same type of cancer cells as chronic lymphocytic leukemia (CLL). When in the blood, it is called small lymphocytic leukemia. Both diseases are staged using a different system from the Lugano system. In the United States, the Rai system is used, while in Europe, the Binet system is used.

Read more about the stages of NHL.

Subtypes of Non-Hodgkin Lymphoma

Non-Hodgkin lymphoma is a term that covers all lymphomas not classified as Hodgkin lymphoma. There are as many as 60 different subtypes of NHL, according to the World Health Organization. NHLs can be grouped into broad categories based on the type of lymphocytes involved — B cells, T cells, or nature killer (NK) cells — and whether the lymphoma is aggressive or indolent (slow-growing). Identifying the subtype of NHL helps doctors determine the best treatment and the prognosis (outlook) for treatment.

B-Cell Lymphomas

B-cell lymphomas arise from B cells, the white blood cells that make antibodies. Mature B-cell lymphomas account for 85 percent to 90 percent of all NHLs. The most common lymphoma of this type is diffuse large B-cell lymphoma, an aggressive NHL. The most common indolent B-cell lymphoma is follicular lymphoma. Other significant mature B-cell lymphomas include:

T-Cell and NK-Cell Lymphomas

T-cell lymphomas arise from T cells, another type of white blood cell important for protection from disease. NK-cell lymphomas arise from natural killer cells, white blood cells that can destroy tumor cells and cells infected with viruses. Mature T-cell and NK-cell lymphomas make up 10 percent to 15 percent of all NHLs.

The most common aggressive lymphomas of this type are:

  • Peripheral T-cell lymphoma
  • Systemic anaplastic large-cell lymphoma
  • Lymphoblastic lymphoma

Some indolent lymphomas of this type include:

Read more about types of non-hodgkin lymphoma.

Treatment of Non-Hodgkin Lymphoma

Your doctor will determine the best course of treatment based on the subtype, stage, and your age and overall health. The goal of treatment can vary depending on the type of NHL. Some lymphomas can be treated with an expectation of full remission, while others can be controlled and kept in check by treatment.

Chemotherapy

Chemotherapy for NHL varies by subtype and may involve different combinations of chemotherapy drugs and steroids. One of the most commonly used chemotherapy regimens for non-Hodgkin lymphomas is R-CHOP, which uses a combination of:

  • Rituximab (sold as Rituxan)
  • Cyclophosphamide (sold as Cytoxan)
  • Doxorubicin (also known as hydroxydaunorubicin and sold as Adriamycin)
  • Vincristine sulfate (formerly sold as Oncovin)
  • Prednisone

Radiation

Radiation therapy is the primary treatment for some indolent lymphomas. It can be used to treat localized problems, such as erosion or pressure of a lymphoma mass upon an organ. Whole-body radiation is also sometimes used to destroy all of a person’s bone marrow before performing a stem cell transplant, but this treatment is becoming less common.

Targeted Therapy

Targeted therapy includes immunotherapy with monoclonal antibodies, treatment with small-molecule drugs, and chimeric antigen receptor (CAR) T-cell therapy.

Monoclonal antibody therapy uses antibodies developed to attach to specific proteins found on the surface of cancer cells. Sometimes chemotherapy drugs are attached to the antibodies.

Small-molecule drugs are drugs that can enter directly into cancer cells and interfere with their ability to grow and replicate.

CAR T-cell therapy uses a person’s own T cells, which are harvested and altered in a lab to add a receptor that binds to specific cancer cell proteins (antigens). Then, the cells are reintroduced into the body. The CAR T-cells can then specifically target cancer cells. The U.S. Food and Drug Administration has approved this treatment for relapsed or refractory lymphoma.

Stem Cell Transplant

Stem cell transplantation is frequently used with high-dose chemotherapy. In an autologous stem cell transplant, stem cells are collected from a person’s own blood or bone marrow prior to chemotherapy. They are then transplanted back into the blood or bone marrow. If using a person’s own stem cells does not work, stem cells from another person may be used, called an allogeneic stem cell transplant.

Clinical Trials

New and experimental treatments are constantly being developed and tested in clinical trials. New drugs, new combinations of chemotherapy drugs, and experimental therapies may offer hope to people who have not responded to current therapies or who cannot tolerate standard treatments.

Palliative Care

Another important part of any cancer treatment plan is palliative care, which aims to help with complications associated with cancer and treatment. Palliative care is focused on improving quality of life by treating symptoms caused by illness and treatment. Palliative care can also help you find emotional and spiritual support for you and your caregivers.

Learn about treatments for lymphoma in detail.

Prognosis for Non-Hodgkin Lymphoma

Non-Hodgkin lymphoma tends to have a good prognosis (outlook), especially in earlier stages. A diagnosis of stage 1 NHL has a five-year survival rate of 84 percent. The overall five-year survival rate for all stages combined, according to the American Cancer Society, is about 73 percent. Your doctor will likely use a tool called the International Prognostic Index to predict your individual disease outlook based on your unique case and risk factors.

Talk With Others Who Understand

MyLymphomaTeam is the social network for people with lymphoma and their loved ones. On MyLymphomaTeam, more than 8,500 members come together to ask questions, give advice, and share their stories with others who understand life with lymphoma.

Are you or someone you care for living with non-Hodgkin lymphoma? Share your experience in the comments below, or start a conversation by posting on MyLymphomaTeam.

References
  1. What Is Lymphoma? — Lymphoma Action
  2. Cancer Stat Facts: Non-Hodgkin Lymphoma — National Cancer Institute
  3. Lymphoma — Centers for Disease Control and Prevention
  4. Non-Hodgkin Lymphoma Risk Factors — American Cancer Society
  5. Symptoms of Lymphoma — Lymphoma Action
  6. Non-Hodgkin Lymphoma — Symptoms — Cancer Research UK
  7. Biopsies — Johns Hopkins Medicine
  8. Tests for Non-Hodgkin Lymphoma — American Cancer Society
  9. Tests, Scans and Staging for Lymphoma — Lymphoma Action
  10. Understanding Your Lab Test Results — American Cancer Society
  11. Staging and Response Assessment in Lymphomas: The New Lugano Classification — Chinese Clinical Oncology
  12. What Is Non-Hodgkin Lymphoma? — American Cancer Society
  13. NHL Subtypes — Leukemia & Lymphoma Society
  14. Chemotherapy and Other Drug Therapies — Leukemia & Lymphoma Society
  15. Understanding Non-Hodgkin Lymphoma (Lymphoid Neoplasms) — Lymphoma Research Foundation
  16. Radiation Therapy — Leukemia & Lymphoma Society
  17. Targeted Therapy (Precision Medicine) — MD Anderson Cancer Center
  18. Monoclonal Antibodies and Their Side Effects — American Cancer Society
  19. Immunotherapy for Non-Hodgkin Lymphoma — American Cancer Society
  20. Targeted Therapy Drugs for Non-Hodgkin Lymphoma — American Cancer Society
  21. Chimeric Antigen Receptor (CAR) T-Cell Therapy — Leukemia & Lymphoma Society
  22. Clinical Trials: What You Need To Know — American Cancer Society
  23. Palliative Care in Cancer — National Cancer Institute
  24. How Is Chronic Lymphocytic Leukemia Staged? — American Cancer Society
  25. High-Dose Chemotherapy and Stem Cell Transplant for Non-Hodgkin Lymphoma — American Cancer Society
  26. Lymphoma — Non-Hodgkin: Statistics — Cancer.Net
  27. Survival Rates and Factors That Affect Prognosis (Outlook) for Non-Hodgkin Lymphoma — American Cancer Society
All updates must be accompanied by text or a picture.
Mark Levin, M.D. is a hematology and oncology specialist with over 37 years of experience in internal medicine. Review provided by VeriMed Healthcare Network. Learn more about him here.
Kristopher Bunting, M.D. studied chemistry and life sciences at the U.S. Military Academy, West Point, and received his doctor of medicine degree from Tulane University. Learn more about him here.

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