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Non-Hodgkin Lymphoma

Non-Hodgkin lymphoma (NHL) is a blood cancer that develops in the lymphatic system. It usually starts in the lymphocytes, which are a type of white blood cell, and because lymphocytes are all over the body, it can grow in other parts of the body as it travels through the blood and lymphatic system.

The World Health Organization has identified more than 60 different subtypes of NHL. Most are classified as B-cell lymphomas or T-cell lymphomas depending on what type of cell they affect. The most common types of NHL are diffuse large B-cell lymphoma and follicular lymphoma. For both of these, survival rates are high.

There are many treatments available for NHL, including chemotherapy, radiation, immunotherapy and targeted therapy. Because non-Hodgkin lymphoma is one of the most common cancers in the United States, options for support and treatment are numerous and improving on a consistent basis.

What Is Non-Hodgkin Lymphoma?

Non-Hodgkin lymphoma (NHL) is a blood cancer that occurs when a white blood cell called a lymphocyte develops mistakes and makes too many copies of itself, and doesn’t die when it should. NHL usually begins in the lymph nodes — areas of the body where lymphocytes collect such as blood vessels and organs — but can spread and grow anywhere in the body.

NHL is generally categorized into two main groups: B-cell lymphomas and T-cell lymphomas. According to the Lymphoma Research Foundation, the three most common types of NHL in the United States are diffuse large B-cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma and follicular lymphoma.

There are more than 60 different types of NHL and the disease is more common in adults than children.

What’s the Difference Between Hodgkin Lymphoma and Non-Hodgkin Lymphoma?

There are two main types of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Both diseases begin in your lymphatic system — specifically in a lymphocyte, which is a type of white blood cell. The primary difference between the two is the presence of Reed-Sternberg cells, a type of cancer cell derived from B lymphocytes. If Reed-Sternberg cells are present, the cancer is classified as Hodgkin lymphoma; if they are not present, it is diagnosed as non-Hodgkin lymphoma. Despite their similar names, these two diseases are very different, both in how they behave and in how they are treated.

Non-Hodgkin Lymphoma Symptoms

The first and most common symptom of NHL is a painless, swollen lymph node. These can occur anywhere in the body but are usually noticed in the neck, armpit or groin.

Several other conditions can cause swelling of the lymph nodes, but if a lymph node continues to increase in size, or if new lumps develop in the same area or in other parts of the body or a person has other symptoms, this may be because of NHL.

Other symptoms of NHL often include one or more of the following:

  • fever
  • fatigue
  • chills
  • abdominal pain or pressure
  • frequent infections
  • drenching night sweats
  • weight loss

Non-Hodgkin Lymphoma Causes

Like many forms of cancer, changes to your genes, also known as genetic mutations, can trigger cells to multiply when they shouldn’t and to not die when they should.

Although doctors and researchers do not currently know all of the mutations that cause NHL, many have been identified. These include a translocation (swapping of genetic material) between chromosomes 14 and 18, which results in the BCL-2 oncogene. An oncogene is a gene that can potentially cause cancer.

Non-Hodgkin Lymphoma Risk Factors

There are several known risk factors for developing NHL.


This is the most significant factor in developing lymphoma, as the disease most commonly occurs in those over the age of 60.


While certain types of NHL are more common in women, men make up the majority of NHL cases.

Race/Ethnicity and Place of Residence

NHL is more common in Caucasians than in African Americans; and specific types of lymphoma are also more common in Latino populations than other populations. NHL is more prevalent in developed countries.

Exposure to Chemicals or Drugs

Exposure to benzene may increase your risk of having NHL. Additionally, some chemotherapy drugs increase the chances of developing NHL, as well as certain medication prescribed for autoimmune diseases, such as methotrexate and tumor necrosis factor (TNF) inhibitors.

Breast Implants

In rare cases, people with breast implants can develop a type of anaplastic large cell lymphoma associated with the implant.

Exposure to Radiation

This includes exposure to nuclear events as well as radiation therapy.

Certain Autoimmune Diseases

Rheumatoid arthritis, systemic lupus erythematosus, Sjogren (Sjögren) disease and celiac disease have been linked to NHL.

Certain Infections

Some viruses may alter the DNA of lymphocytes, which can increase the risk of NHL. These include human immunodeficiency virus (HIV), human T-cell lymphotropic virus (HTLV-1), Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV-8).

Non-Hodgkin Lymphoma Diagnosis

If you develop NHL symptoms, your doctor will likely recommend a physical exam followed by a biopsy to confirm or rule out the disease.

  • Physical Exam: First, your doctor is likely to perform a physical exam, paying special attention to your lymph nodes. They will also likely ask about your symptoms and family medical history.
  • Biopsy: If your doctor finds any swollen lymph nodes during the physical exam, they will likely order a biopsy to examine a lymph node or part of a lymph node. A biopsy is the only way to confirm a case of NHL.
    The most common biopsy types used in diagnosing NHL are excisional biopsies, during which a surgeon removes an entire lymph node, and a core biopsy or fine-needle aspiration, during which only a section of the lymph node is removed.
    Core biopsies and fine needle aspirations can be performed using a local anesthetic while excisional biopsies may require general sedation or anesthesia.

Is a Bone Marrow Biopsy Necessary to Diagnose Non-Hodgkin Lymphoma?

Bone marrow biopsies can be used to see if NHL has spread to a patient’s bone marrow and can help doctors stage the disease in certain instances. In some contexts, these are necessary and in some, they are not.

I’ve Been Diagnosed with Non-Hodgkin Lymphoma, Now What?

Ask your doctor how to proceed. If possible, consult an oncologist who specializes in treating NHL. With telemedicine, you may even be able to speak to a lymphoma specialist from the comfort of your own home. With NHL, it’s important to find out what type you have because different subtypes of the disease respond better to certain treatments than others. Ask your doctor for your exact diagnosis, including what type of lymphoma you have, your prognosis and goals of treatment. This discussion will help guide you in making informed decisions about your treatment.

Non-Hodgkin Lymphoma Stages

Non-Hodgkin lymphoma is staged based on the location of the cancer and how many lymph node regions are affected.

Stage I: Lymphoma is found in a single lymph node region plus or minus nearby tissue.

Stage II: Lymphoma is found in two or more lymph node regions on the same side of the diaphragm, either above or below it.

Stage III: Lymphoma is found in lymph nodes on both sides of the diaphragm.

Stage IV: The cancer is in one or more tissues or organs outside the lymphatic system, such as the liver, lungs, or bones, and may also be found in lymph nodes near or far away from those parts of the body.

In addition to staging non-Hodgkin lymphoma, doctors also grade this type of cancer-based on the growth pattern and aggressiveness of the cells:

  • Low Grade: indolent or slow-growing
  • Intermediate Grade: moderate growth rate
  • High Grade: aggressive or rapidly growing

The grade and stage are both important factors when doctors are evaluating treatment plans and prognosis.

Non-Hodgkin Lymphoma Treatment

If your NHL is indolent (slow to grow), you and your treating doctor may decide to take a watch-and-wait approach. This means delaying treatment until needed, while closely monitoring for disease progression.

If you are having symptoms, have an aggressive lymphoma or have problems caused by NHL, you may need treatment, which may consist of chemotherapy, immunotherapy and/or radiation therapy. Treatment may also include targeted therapies or stem-cell transplants.


Chemotherapy consists of strong drugs that kill or damage cancer cells. The types of chemotherapy drugs regularly used for treating NHL include alkylating agents, anthracyclines, anti-metabolites, corticosteroids, platinum drugs and purine analogs. These are often combined.

Radiation Therapy

Radiation therapy is used as part of or the only treatment for some types of NHL.


Immunotherapy helps a patient’s own immune system kill cancer cells using monoclonal antibodies, which are man-made versions of antibodies, to target a specific protein on lymphoma cells or immune checkpoint inhibitors, which help a body’s cells detect and fight against cancer cells. Examples of immunotherapy include pembrolizumab (Keytruda) and immunomodulating drugs (which help the immune system fight cancer although not much is known about exactly how they work) such as lenalidomide (Revlimid). CAR-T can also be used to treat NHL that has relapsed or not responded to therapy. CAR-T uses a patient’s T-cells, which are removed and altered in a lab to add specific receptors on their surface, making them more able to kill NHL. The cells are then multiplied and re-introduced into the patient’s blood.

Targeted Therapies

Targeted therapies are drugs designed to attack lymphoma cells specifically. They include proteasome inhibitors, histone deacetylase (HDAC) inhibitors, Bruton tyrosine kinase (BTK) inhibitors, PI3K inhibitors, EZH2 inhibitors and nuclear export inhibitors.

Stem Cell Transplants

Stem cell transplants are used in combination with very high-dose chemotherapy that wipes out a patient’s bone marrow. First, a patient’s stem cells are collected, then a large dose of chemotherapy is given to a patient, and then the patient’s stem cells are given back to them to regrow all the cells in the patient’s bone marrow.

Here are a few questions to ask when discussing treatment options with your doctor:

  • What type of non-Hodgkin lymphoma do I have?
  • Which treatment option/s do you recommend, and why?
  • Is my lymphoma indolent or aggressive?
  • Do I need to start treatment right away?
  • How long will treatment last?
  • What are the risks or side effects?

Non-Hodgkin Lymphoma Survival

With more than 60 different types of NHL, survival rates vary widely. In general, however, survival rates for NHL are high. According to Surveillance, Epidemiology, and End Results (SEER) data, published by the National Cancer Institute, the relative five-year survival rate from 2010 to 2016 was 72.7%. In cases of non-localized NHL (meaning the disease has spread to other parts of the body), the five-year survival rate is 61.6%. The ten-year survival rate is 60%. This means that approximately 60 out of 100 people diagnosed with NHL were still alive ten years after their diagnosis.

Non-Hodgkin Lymphoma  FAQs

What is Follicular Lymphoma?

This disease is a subtype of non-Hodgkin lymphoma B-cell lymphoma, meaning that it affects B-lymphocytes. According to the Lymphoma Research Foundation, follicular lymphoma accounts for approximately 20% to 30% of all NHL cases. Follicular lymphoma cannot usually be cured. However, the disease is very slow-growing. Patients often have no symptoms at diagnosis, and often live with the disease for decades. However, follicular lymphoma can be variable and, in some patients, it may not respond well to treatment or may transform into a more aggressive lymphoma.

What is Indolent Non-Hodgkin Lymphoma?

The word indolent refers to something that is slow-moving or lethargic, and likewise, indolent NHL is a form of the disease that grows and progresses very slowly. Because of this, patients may not experience any symptoms at all and may not require immediate treatment. Additionally, because indolent NHL is slow-moving, the average life expectancy is a robust 12 to 14 years. Follicular lymphoma is a type of indolent NHL.

What is Diffuse Large B-Cell Lymphoma?

Diffuse large B-cell lymphoma (DLBCL) is an aggressive form of NHL that affects the body’s B-lymphocytes, which are a type of white blood cell responsible for the production of antibodies. This is the most common form of NHL both in the United States and around the world, with more than 18,000 people diagnosed with diffuse large B-cell lymphoma each year. DLBCL is fast-growing and can often be cured.

Is CAR T-Cell Therapy Approved for Follicular Lymphoma?

Yes. Follicular lymphoma is often an indolent, or slow-spreading form of NHL, but occasionally follicular lymphoma does not respond to therapy, returns quickly or transforms to more aggressive lymphomas. In those instances, CAR-T has been shown to be effective in treating follicular lymphoma.

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