Non-Hodgkin lymphoma

What is Non-Hodgkin’s lymphoma?

Non-Hodgkin lymphoma is a cancer that starts in the lymphatic system, which is part of the body’s immune system. White blood cells called lymphocytes proliferate improperly in non-lymphoma Hodgkin’s and can form tumours throughout the body.

Non-Hodgkin lymphoma is a type of lymphoma that is not Hodgkin’s lymphoma. This category encompasses a wide range of subcategories. The most prevalent subtypes are diffuse large B-cell lymphoma and follicular lymphoma. Hodgkin’s lymphoma is the other major type of lymphoma.

The prognosis for persons with Non-Hodgkin lymphoma has improved thanks to advances in diagnosis and therapy.

NHL is a term that’s used for many different types of lymphoma that all share some of the same characteristics. There is another main type of lymphoma, called Hodgkin lymphoma, which is treated differently.

Lymphoma affects the body’s lymph system (also known as the lymphatic system). The lymph system is part of the immune system, which helps fight infections and some other diseases. It also helps fluids move through the body.

Where lymphoma starts ?

Lymphomas can start anywhere in the body where lymph tissue is found. The major sites of lymph tissue are:

  • Lymph nodes: Lymph nodes are bean-sized collections of lymphocytes and other immune system cells throughout the body, including inside the chest, abdomen, and pelvis. They are connected by a system of lymphatic vessels.
  • Spleen: The spleen is an organ under the lower ribs on the left side of the body. The spleen makes lymphocytes and other immune system cells. It also stores healthy blood cells and filters out damaged blood cells, bacteria, and cell waste.
  • Bone marrow: The bone marrow is the spongy tissue inside certain bones. This is where new blood cells (including some lymphocytes) are made.
  • Thymus: The thymus is a small organ behind the upper part of the breastbone and in front of the heart. It’s important in the development of T lymphocytes.
  • Adenoids and tonsils: These are collections of lymph tissue in the back of the throat. They help make antibodies against germs that are breathed in or swallowed.
  • Digestive tract: The stomach, intestines, and many other organs also have lymph tissue.

Types of non-Hodgkin lymphoma

  • Chronic lymphocytic leukemia
  • Cutaneous B-cell lymphoma
  • Cutaneous T-cell lymphoma
  • Follicular lymphoma
  • Waldenstrom macroglobulinemia

Treatment for NHL depends on which type it is, so it’s important for doctors to find out the exact type of lymphoma you have. The type of lymphoma depends on what type of lymphocyte is affected (B cells or T cells), how mature the cells are when they become cancerous, and other factors. 

B-cell vs T-cell lymphomas

The lymph system is made up mainly of lymphocytes, a type of white blood cell that helps the body fight infections. There are 2 main types of lymphocytes:

  • B lymphocytes (B cells): B cells normally help protect the body against germs (bacteria or viruses) by making proteins called antibodies. The antibodies attach to the germs, marking them for destruction by other parts of the immune system.
  • T lymphocytes (T cells): There are several types of T cells. Some T cells destroy germs or abnormal cells in the body. Other T cells help boost or slow the activity of other immune system cells.

Lymphoma can start in either type of lymphocytes, but B-cell lymphomas are most common.

Indolent vs. aggressive lymphomas

Types of NHL can also be grouped based on how fast they grow and spread:

  • Indolent lymphomas grow and spread slowly Some indolent lymphomas might not need to be treated right away, but can be watched closely instead. The most common type of indolent lymphoma in the United States is follicular lymphoma.
  • Aggressive lymphomas grow and spread quickly, and usually need to be treated right away. The most common type of aggressive lymphoma in the United States is diffuse large B cell lymphoma (DLBCL).
  • Some types of lymphoma, like mantle cell lymphoma, don’t fit neatly into either of these categories.

Regardless of how quickly they grow, all non-Hodgkin lymphomas can spread to other parts of the lymph system if not treated. Eventually, they can also spread to other parts of the body, such as the liver, brain, or bone marrow.

Classifying types of NHL

There are many different types of non-Hodgkin lymphoma (NHL), so classifying it can be quite confusing (even for doctors). Several different systems have been used, but the most recent system is the World Health Organization (WHO) classification. The WHO system groups lymphomas based on: 

  • The type of lymphocyte the lymphoma starts in
  • How the lymphoma looks under a microscope
  • The chromosome features of the lymphoma cells
  • The presence of certain proteins on the surface of the cancer cells

Symptoms of non-Hodgkin’s lymphoma

Signs and symptoms of non-Hodgkin’s lymphoma may include:

  • Swollen lymph nodes in your neck, armpits or groin
  • Abdominal pain or swelling
  • Chest pain, coughing or trouble breathing
  • Persistent fatigue
  • Fever
  • Night sweats
  • Unexplained weight loss

Risk factors for non-Hodgkin lymphoma

Anything that enhances your chances of having a disease like cancer is considered a risk factor. The risk factors for various malignancies varies. Some risk factors, such as smoking, are modifiable. Others, such as a person’s age or family history, are impossible to determine.

However, just because you have a risk factor, or even several risk factors, does not indicate you will develop the disease. Furthermore, many persons who have the condition have little or no established risk factors.

Researchers have discovered a number of factors that can influence a person’s risk of developing non-Hodgkin lymphoma (NHL). There are many different varieties of lymphoma, and some of these characteristics have only been related to certain types of lymphoma.

  • Age: Getting older is a strong risk factor for lymphoma overall, with most cases occurring in people in their 60s or older . But some types of lymphoma are more common in younger people.
  • Gender: Overall, the risk of NHL is higher in men. than in women , but there are certain types of NHL that are more common in women. The reasons for this are not known.
  • Family history: Having a first degree relative (parent, child, sibling) with NHL increases your risk of developing NHL.
  • Drugs & chemical exposure: Chemicals like benzene and some herbicides and insecticides (weed- and insect-killing compounds) have been associated to an elevated risk of NHL in some studies. The investigation into these suspected connections is currently ongoing.

    Some chemotherapy medicines used to treat other malignancies have been linked to an increased risk of acquiring NHL several years later. Patients who have been treated for Hodgkin lymphoma, for example, have a higher risk of acquiring NHL later. However, it’s unclear whether this is related to the sickness or a side effect of the treatment.

    Certain medicines used to treat rheumatoid arthritis (RA), such as methotrexate and tumour necrosis factor (TNF) inhibitors, have been linked to an increased risk of NHL in some studies. Other studies, on the other hand, have shown no evidence of an increased risk. The fact that persons with RA, an autoimmune disease, already have a higher risk of NHL complicates determining if these medicines enhance risk.

  • Exposure to radiation:

    Survivors of atomic bombs and nuclear reactor accidents have an elevated risk of getting cancers such as NHL, leukaemia, and thyroid cancer, according to studies.

    Patients who have received radiation therapy for other malignancies, such as Hodgkin lymphoma, are at a slightly higher risk of acquiring NHL later in life. Patients who receive both radiation therapy and chemotherapy are at a higher risk.

  • Weak immune system: People with weakened immune systems have an increased risk for NHL. For example:

    People who receive organ transplants are treated with drugs that suppress their immune system to prevent it from attacking the new organ. These people have a higher risk of developing NHL.
    The human immunodeficiency virus (HIV) can weaken the immune system, and people infected with HIV are at increased risk of NHL.
    In some genetic (inherited) syndromes, such as ataxia-telangiectasia (AT) and Wiskott-Aldrich syndrome, children are born with a deficient immune system. Along with an increased risk of serious infections, these children also have a higher risk of developing NHL.

  • Autoimmune diseases:

    Rheumatoid arthritis, systemic lupus erythematosus (SLE or lupus), Sjogren’s disease, celiac disease (gluten-sensitive enteropathy), and other autoimmune illnesses have all been associated to a higher risk of NHL.

    The immune system misidentifies the body’s own tissues as foreign and assaults them as it would a germ in autoimmune illnesses. Lympocytes (the cells that give rise to lymphomas) are immune system cells. Lympocytes may develop and divide more often than normal due to an overactive immune system in autoimmune disorders. This could make them more likely to become lymphoma cells.

  • Infections: Some types of infections may raise the risk of NHL in different ways. Infections that directly transform lymphocytes. Some viruses can directly affect the DNA of lymphocytes, helping to transform them into cancer cells:

    Infection with human T-cell lymphotropic virus (HTLV-1) increases a person’s risk of certain types of T-cell lymphoma. This virus is most common in some parts of Japan and in the Caribbean region, but it’s found throughout the world. In the United States, it causes less than 1% of lymphomas. HTLV-1 spreads through sex and contaminated blood and can be passed to children through breast milk from an infected mother.
    Infection with the Epstein-Barr virus (EBV) is an important risk factor for Burkitt lymphoma in some parts of Africa. In developed countries such as the United States, EBV is more often linked with lymphomas in people also infected with HIV, the virus that causes AIDS. EBV has also been linked with some less common types of lymphoma.
    Human herpes virus 8 (HHV-8) can also infect lymphocytes, leading to a rare type of lymphoma called primary effusion lymphoma. This lymphoma is most often seen in patients who are infected with HIV. HHV-8 infection is also linked to another cancer, Kaposi sarcoma. For this reason, another name for this virus is Kaposi sarcoma-associated herpes virus (KSHV).

  • Infections that weaken the immune system:
    Infection with human immunodeficiency virus (HIV), also known as the AIDS virus, can weaken the immune system. HIV infection is a risk factor for developing certain types of NHL, such as primary CNS lymphoma, Burkitt lymphoma, and diffuse large B-cell lymphoma.

  • Infections that cause chronic immune stimulation:
    Some long-term infections may increase a person’s risk of lymphoma by forcing their immune system to be constantly active. As more lymphocytes are made to fight the infection, there is a greater chance for mutations in key genes to occur, which might eventually lead to lymphoma. Some of the lymphomas linked with these infections actually get better when the infection is treated.

    Helicobacter pylori, a type of bacteria known to cause stomach ulcers, has also been linked to mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach.
    Chlamydophila psittaci (formerly known as Chlamydia psittaci) is a type of bacteria that can cause a lung infection called psittacosis. It has been linked to MALT lymphoma in the tissues around the eye (called ocular adnexal marginal zone lymphoma).
    Infection with the bacterium Campylobacter jejuni has been linked to a type of MALT lymphoma called immunoproliferative small intestinal disease. This type of lymphoma, which is also sometimes called Mediterranean abdominal lymphoma, typically occurs in young adults in eastern Mediterranean countries.
    Long-term infection with the hepatitis C virus (HCV) seems to be a risk factor for certain types of lymphoma, such as splenic marginal zone lymphoma .
    Body weight
    Some studies have suggested that being overweight or obese might increase your risk of NHL. More research is needed to confirm these findings. In any event, staying at a healthy weight, keeping physically active, and following a healthy eating pattern that includes plenty of fruits, vegetables, and whole grains, and that limits or avoids red and processed meats, sugary drinks, and highly processed foods has many known health benefits outside of the possible effect on lymphoma risk.

  • Breast implants:
    Although it is rare, some women with breast implants develop a type of anaplastic large cell lymphoma (ALCL) in their breast. This seems to be more likely with implants that have textured (rough) surfaces (as opposed to smooth surfaces).

Diagnosis of non-Hodgkin lymphoma

Your doctor will likely ask you about your personal and family medical history. He or she may then have you undergo tests and procedures used to diagnose non-Hodgkin’s lymphoma, including:

  • Physical exam. Your doctor checks for swollen lymph nodes, including in your neck, underarm and groin, as well as for a swollen spleen or liver.
  • Blood and urine tests. Blood and urine tests may help rule out an infection or other disease.
  • Imaging tests. Your doctor may recommend imaging tests to look for signs of lymphoma cells elsewhere in your body. Tests may include CTMRI and positron emission tomography (PET).
  • Lymph node test. Your doctor may recommend a lymph node biopsy procedure to remove all or part of a lymph node for laboratory testing. Analyzing lymph node tissue in a lab may reveal whether you have non-Hodgkin’s lymphoma and, if so, which type.
  • Bone marrow test. A bone marrow biopsy and aspiration procedure involves inserting a needle into your hipbone to remove a sample of bone marrow. The sample is analyzed to look for non-Hodgkin’s lymphoma cells.
  • Lumbar puncture (spinal tap). If there’s a concern that the lymphoma may affect the fluid around your spinal cord, your doctor might recommend a procedure to remove some of the fluid for testing. During a spinal tap, the doctor inserts a small needle into the spinal canal in your lower back.

Treatment of non-Hodgkin lymphoma

There are a number of non-Hodgkin lymphoma (NHL) treatments available. The specifics of your lymphoma, such as the types of cells involved and if your lymphoma is aggressive, will determine which treatment or combination of treatments is best for you. Your doctor will also take into account your overall health and preferences.

You might not need therapy right away if your lymphoma appears to be slow-growing (indolent) and doesn’t create any signs or symptoms. Instead, your doctor may suggest that you have routine checks every few months to evaluate your health and see if your cancer is progressing.

Your doctor may recommend therapy if your non-Hodgkin lymphoma (NHL)is aggressive or creates signs and symptoms. Among the possibilities are:


Chemotherapy is a pharmacological treatment for cancer cells that kills them. It can be taken orally or intravenously. Chemotherapy medications can be used on their own, with additional chemotherapy agents, or in combination with other treatments.

For non-Hodgkin lymphoma (NHL), chemotherapy is a popular first-line treatment. It’s also a possibility if your lymphoma returns after your initial treatments.

Chemotherapy is also used as part of a bone marrow transplant, also known as a stem cell transplant, for persons with non-lymphoma. Hodgkin’s Chemotherapy at very high doses can help your body prepare for the transplant.

Radiation therapy

To kill cancer cells, radiation therapy uses high-powered energy beams such as X-rays and protons. You lie on a table while receiving radiation therapy, and a big machine revolves around you, directing energy beams to particular locations on your body.

Radiation therapy may be the only therapeutic option for certain kinds of non-Hodgkin lymphoma (NHL) especially if the lymphoma is slow-growing and only affects one or two areas. Radiation is routinely used after chemotherapy to eliminate any remaining lymphoma cells. Radiation can be directed towards the afflicted lymph nodes as well as the surrounding area of nodes where the disease may spread.

Targeted drug therapy

Targeted drug treatments focus on specific abnormalities present within cancer cells. By blocking these abnormalities, targeted drug treatments can cause cancer cells to die.

For non-Hodgkin’s lymphoma, targeted drugs can be used alone, but are often combined with chemotherapy. This combination can be used as your initial treatment and as a second treatment if your lymphoma comes back.

Engineering immune cells to fight lymphoma

A specialized treatment called chimeric antigen receptor (CAR)-T cell therapy takes your body’s germ-fighting T cells, engineers them to fight cancer and infuses them back into your body.

CAR-T cell therapy might be an option for certain types of B-cell non-Hodgkin’s lymphoma that haven’t responded to other treatments.

Bone marrow transplant

Bone marrow transplant, also known as a stem cell transplant, involves using high doses of chemotherapy and radiation to suppress your bone marrow and immune system. Then healthy bone marrow stem cells from your body or from a donor are infused into your blood where they travel to your bones and rebuild your bone marrow.

For people with non-Hodgkin’s lymphoma, a bone marrow transplant might be an option if other treatments haven’t helped.


Immunotherapy is a type of cancer treatment that makes use of your immune system. Because cancer cells create proteins that assist them hide from immune system cells, your body’s disease-fighting immune system may not attack your cancer. Immunotherapy works by interfering with the immune system’s natural processes.

If other therapies have failed, immunotherapy medications may be an option for certain kinds of non-lymphoma. 


CAR T-Cell therapy

CAR T-cell therapy is a viable treatment option for some individuals with non-Hodgkin lymphoma (NHL) who have relapsed or who have failed to respond to prior treatments (refractory). It’s a highly sophisticated treatment that entails genetically altering a patient’s own T cells in order to combat cancer. Several CAR T-cell treatments for lymphoma have been authorized by the FDA. Dana-Farber/Brigham and Women’s Cancer Center (DF/BWCC) is one of the first cancer institutes to offer FDA-approved CAR T-cell therapy to patients who have failed to respond to other treatments.

Apply for CAR T-Cell therapy

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  • December 12th, 2021


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