Patient Information

Non-Hodgkin's Lymphoma

About Non-Hodgkin's Lymphoma (NHL)

A lymphoma is a cancer that affects lymphocytes, a type of white blood cell. There are 2 major categories of lymphomas: non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). These are further subdivided into several types that are different in the way they develop and spread, and in how affected patients are treated.

Lymphomas usually develop when a change, or mutation, occurs within a lymphocyte, causing the abnormal cell to replicate faster than, or live longer than, a normal lymphocyte. Like normal lymphocytes, cancerous lymphocytes can travel through the blood and lymphatic system and spread and grow in many parts of the body, including the lymph nodes, spleen, bone marrow, and other organs. This is why most types of lymphomas are found throughout the body by the time a patient is diagnosed with the disease.

NHL is divided into the following 2 major groups:

  • B-cell lymphomas: These lymphomas develop from abnormal B-lymphocytes (“B” because B-lymphocytes come from the bone marrow) and account for 85 % of all NHL.
  • T/NK-cell lymphomas: These lymphomas develop from abnormal T-lymphocytes (“T” because normally T-lymphocytes spend part of their lifespan in the thymus gland, a small organ in the chest) or natural killer (NK) cells. These account for the remaining 15 % of NHL.

NHL types are also often grouped according to how quickly they grow:

  • Indolent lymphomas (also called low-grade lymphomas) grow slowly and tend to cause few symptoms. While indolent lymphomas are usually not curable, patients can live a long time with these types of lymphomas because they generally respond well to treatment and may potentially remain in remission for many years (even decades). Over time, some indolent lymphomas may transform into aggressive lymphomas.
  • Aggressive lymphomas (also called intermediate-grade and high grade lymphomas) grow and spread more quickly than indolent lymphomas. Aggressive lymphomas, while potentially life threatening, can often be cured with chemotherapy and other newer treatments.

Follicular lymphoma (FL), a B-cell lymphoma, is the most common indolent (slow-growing) form of NHL. Of the more than 66,000 cases of NHL estimated to have been diagnosed in 2008 in the United States, 15-20% were follicular lymphomas.2 FL usually appears in lymph nodes spread throughout the body. Often, one of the first signs of FL is a painless swelling in the neck, armpit, or groin caused by these enlarged lymph nodes. FL may eventually transform into a more aggressive form of the disease.

Stages of NHL:

Ann Arbor staging is used to describe how widely the lymphoma has spread in adult patients with NHL. There are 4 main stages of lymphoma (Stage I-IV), with Stage I indicating localized disease and Stage IV indicating widespread disease.

The doctor may also add any of the following single letters to the stage.

  • A: if patients have not experienced symptoms such as significant weight loss (more than 10% in 6 months), drenching night sweats, or fevers.
  • B: if patients have lost weight (more than 10% in 6 months) and have experienced drenching night sweats or fevers.
  • X: if patients have a lymphoma that is greater than 10 cm (4 inches) wide. This is also called bulky disease.
  • S: if the disease has spread to the spleen.
  • E: if the disease is "extranodal" (not in the lymph nodes) or has spread from lymph nodes to adjacent tissue.

How common is NHL?

The number of new cases of NHL was 19.7 per 100,000 men and women per year. The number of deaths was 6.3 per 100,000 men and women per year. These rates are age-adjusted and based on 2007-2011 cases and deaths. Approximately 2.1 percent of men and women will be diagnosed with NHL at some point during their lifetime, based on 2009-2011 data. In 2011, there were an estimated 530,919 people living with NHL in the United States.3

In 2014, an estimated 70,800 people will be diagnosed with NHL and there will be approximately 19,020 deaths due to the disease.4

Some patients with NHL do not experience any symptoms. Their disease may be detected initially by their doctor during a routine physical examination or only after the tumor becomes large enough to cause symptoms.

Signs and symptoms:

General symptoms of NHL can include:

  • Unexplained weight loss
  • Fever for no known reason
  • Drenching night sweats
  • Severe or frequent infections
  • Easy bruising or bleeding
  • Numbness or tingling in feet and/or hands
  • Headaches and/or blurry vision
  • Fatigue

NHL may cause different signs and symptoms depending on the location of the tumor in the body.

  • Swollen lymph nodes: Lumps under the skin on the sides of the neck, in the groin or underarms, or above the collar bone
  • Enlarged lymph nodes in the abdomen: Accumulation of large amounts of liquid in the abdomen; swollen, tender abdomen
  • Lymphoma in the intestine: Abdominal pain, nausea, or vomiting.
  • Lymphoma of the stomach: Stomach pain, nausea, and decreased appetite
  • Lymphoma in the chest: Cough, trouble breathing, chest pain
  • Lymphoma of the brain: Headache, weakness in certain parts of the body, personality changes, seizures
  • Lymphoma of the skin: Itchy, red, or purple lumps or nodules under the skin

Risk Factors

The characteristics that make a person possibly more susceptible to developing any type of disease are called risk factors. Having 1 or more of these risk factors does not mean a person will develop NHL. In fact, most people with risk factors never develop the disease and many people diagnosed with NHL have never been exposed to any clearly identifiable risk factors.

Risk Factors You Cannot Change5

Age: The risk for developing NHL increases with age.

Gender: Men are affected slightly more than women.

Risk Factors Linked to Things You Do5

Exposure to certain chemicals: Working in the rubber manufacturing industry and occupational and environmental exposure to certain chemicals (e.g., solvents such as dihloromethane) may increase risk of NHL.

Immune Suppressants: Risk of NHL is elevated in people who receive immune suppressants to prevent organ transplant rejection.

Family history: People with family history of lymphoma and confirmed common genetic variations (including variations in the human leukocyte antigen) are at an increased risk of developing NHL.

Certain viral infections: Risk of NHL is elevated in people infected with human immunodeficiency virus (HIV) or human T-cell leukemia virus type I. Epstein Barr virus causes Burkitt lymphoma (an aggressive type of NHL that occurs most often in children and young adults).

Certain bacterial infections: Infection with Helicobacter pylori (which may cause stomach ulcers) may increase the risk of developing lymphoma in the stomach lining. Infection with Chlamydophila psittaci may increase the risk of a lymphoma that occurs in the tissues of the eye.

About Treatment1, 4


There are various types of therapies for patients with NHL:

  • Chemotherapy, which affects general cell growth and division
  • Monoclonal antibodies (mAbs) or immunotherapy
  • Radioimmunotherapy
  • Proteasome inhibitors
  • Histone deacetylase (HDAC) inhibitors
  • Immunoconjugates
  • Radiation therapy


Most patients with NHL are treated with combination chemotherapy, meaning 2 or more drugs, instead of a single drug. These chemotherapy drugs are given in a specific order (or schedule) during certain days of each treatment cycle- this is called a treatment regimen. The reason to combine drugs is to increase how effectively they kill or damage cancer cells.

Common chemotherapy regimens for NHL include:

  • CHOP: Cyclophosphamide, Doxorubicin, Vincristine, Prednisone
  • DHAP: Dexamethasone, Cytarabine, Cisplatin
  • EPOCH: Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin
  • CVP (COP): Cyclophosphamide, Vincristine, Prednisone
  • CHOEP: Cyclophosphamide, hydroxydaunorubicin, vincristine, etoposide, prednisone
  • ESHAP: Etoposide, Methylprednisolone, Cisplatin, Cytarabine
  • HyperCVAD/MTX-Ara-C: Cyclophosphamide, Vincristine, Doxorubicin, Dexamethasone, Methotrexate, Cytarabine

Monoclonal antibodies (mAb)

Monoclonal antibodies are molecules made in the laboratory that are designed to recognize and stick to specific molecules on, for example, cancer cells. When a monoclonal antibody attaches itself to a cancer cell, it can stop or slow down its growth or it can make it easier for the immune system to recognize it and kill it. The monoclonal antibody rituximab (Rituxan) is approved by the FDA to treat patients with NHL.

With the emergence of rituximab resistance, next-generation anti-CD20 mAbs have been developed to augment effector-function potency and increase CD20 binding avidity. Second (ocrelizumab, veltuzumab, and ofatumumab) and third-generation anti-CD20 antibodies have been developed and are in clinical trials.


Radioimmunotherapy employs mAb or mAb-derived vectors that are chemically conjugated to radioactive isotopes for tumor targeting and delivery. This allows delivery of a radioisotope at the cellular level.


This is a combination of a monoclonal antibody against CD30 (brentuximab) attached to the small toxic drug monomethyl auristatin E (vedotin or MMAE). The monoclonal antibody part of this drug attaches itself to lymphoma cells that express CD30 antigen, causing them to transport the drug into the cells. Once inside cells, the MMAE drug is separated from the antibody molecule. The MMAE attacks and breaks up an internal support skeleton (called the microtubule network) of the cells, causing them to stop dividing and die. Brentuximab vedotin (Adcetris) is a FDA approved drug.

Proteasome inhibitors

Inhibit the ability of cells to properly dispose of proteins. Proteasome inhibition causes an abnormal build-up of proteins in a cancerous cell, resulting in cell death. Bortezomib is approved for the treatment of relapsed mantle cell lymphoma, a type of NHL.

Histone deacetylase (HDAC) inhibitors

Interact with chromosomes in such a way to trigger the production of proteins that normally would have been blocked by the cell. HDAC inhibitors typically result in a cancer cell expressing proteins that interfere with its ability to grow and survive. Currently, there are 2 HDAC inhibitors approved for the treatment of NHL: romidepsin (Istodax) and vorinostat (Zolinza).

Radiation Therapy

Radiation therapy (also called radiotherapy) uses high-energy x-rays or other types of radiation to kill cancer cells and shrink tumors. The term is used typically to describe external radiotherapy, in which radiation is delivered using an external radiation beam.


1. Cancer Management and Research. Treatment challenges in the management of relapsed or refractory non-Hodgkin’s lymphoma – novel and emerging therapies. 2013 (5): 251–269.
2. Freytes CO, et al. Follicular Lymphoma Management Overview. Available at Last accessed on 16-Dec-2014.
3. SEER Stat Fact Sheets: Non-Hodgkin Lymphoma. Available at . Last accessed on 16-Dec-2014.
4. NCCN Clinical Practice Guidelines in Oncology for Non-Hodgkin’s Lymphoma. Version 5. 2014
5. American Cancer Society. Cancer Facts & Figures 2014. Atlanta, Ga: American Cancer Society; 2014. Available at