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Non-Hodgkin Lymphoma
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This is the American Society of Clinical Oncology's patient information web site. It provides oncologist-approved information on more than 50 types of cancer and their treatments, clinical trials, coping and side effects. The site includes sections on both adult and childhood non-Hodgkin lymphoma.
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Finding an appropriate clinical trial can be daunting so the Coalition of Cancer Cooperative Groups recently introduced this new Web site which offers an online screening questionnaire that helps identify specific clinical trials that match disease type, age, medical history and other criteria
Some 750 clinical trials for non-Hodgkin's lymphoma are currently recruiting patients. This site offers information about the latest promising therapies.
The Leukemia & Lymphoma Society (LLS) is the world's largest voluntary health organization dedicated to funding blood cancer research, education and patient services. They provide information on these diseases through both online and in-person group support. The web site includes live patient help, a chapter finder and comprehensive information on all aspects of NHL.
LRFA raises money for research and provides patient support and information. It was founded in 1991 by a patient with NHL. The Web site includes details of services, information about lymphoma, research grants etc.
This U.S. government site provides information on non-Hodgkin's disease treatment, screening, prevention, genetics, clinical trials and supportive care. They have identified 63 centers around the country that conduct state-of-the-art research in diagnosis and treatment of cancer. You can locate one on the Web at
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While other cancers continue to decline, lymphoma is on the rise. The good news is that with early diagnosis, Non-Hodgkin Lymphoma is often a very treatable disease with a good prognosis.


It's one of the fastest rising cancers in the United States.1 It's the sixth most common cancer among males,2 the fifth most common cancer among females2 and accounts for about 6 percent of childhood cancers.3   In 2008, over 66,000 Americans will be diagnosed with it, and over 19,000 will die from it.4 It claimed the lives of Jacqueline Kennedy Onassis and King Hussein of Jordan.  It's non-Hodgkin lymphoma (NHL).

What is lymphoma?

Like all cancers, lymphoma causes cells to abnormally reproduce, eventually causing tumors to grow.  There are both similarities and differences between the two main categories of lymphoma – Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL).  Both originate in a type of white blood cell known as a lymphocyte, which is found within the lymph nodes or lymphoid tissue within other organs. But, they grow and spread in different ways, and the treatments that work best are different for each.  Doctors distinguish between them by looking for one type of cell (the Reed Sternberg cell) that's found only in Hodgkin lymphoma. 

The mysteries of non-Hodgkin lymphoma are just beginning to be unraveled.  Among it's many puzzles:

  • What makes a lymphocyte transform into a lymphoma cell?
  • How does it relate to other lymphomas and leukemias?
  • What are the risk factors?
  • Why is its incidence increasing while many other cancers are trending down?
  • Why does it take a more aggressive form in some people than in others?
  • Why does it manifest differently in children than in adults?

Causes of non-Hodgkin lymphoma

Cause can be established only in a small minority of non-Hodgkin lymphoma cases.  Despite multiple studies, information about risk factors remains inconclusive.  Researchers have found a number of associations with NHL that warrant further study including: 

  • Certain chemical exposures, such as pesticides (insect killers) and herbicides (weed killers)  
  • Some bacteria and viruses, such as the HIV, Hepatitis C and Epstein-Barr viruses
  • Previous chemotherapy or radiation therapy
  • Conditions which weaken the immune system
  • Constant immune system reactions, such as those triggered by allergies
  • Certain genetic and chromosomal abnormalities
  • Long duration and early use of permanent dark hair dyes
  • Nitrates in drinking water from runoff following the use of nitrogen fertilizer by farms
  • Long-term illegal use of narcotic drugs

Symptoms of non-Hodgkin lymphoma

An individual's first inkling that something is wrong is usually a painless swelling of the lymph nodes, usually in the neck, underarm, groin or in the abdomen.  Of course, nodes can swell as a result of a simple infection, but in that instance they're usually tender.  Other symptoms may include:

  • Unexplained fever
  • Excessive sweating and night sweats
  • Excessive fatigue
  • Unintentional weight loss
  • Severe itching
  • Recurring infections
  • And more, depending on the location and spread of the cancer.  These may include:
    • Coughing or shortness of breath if the windpipe is involved
    • Stomach pain, swelling or nausea
    • Bone pain
    • Headaches, problems concentrating, seizures 

There is no screening test for non-Hodgkin lymphoma and diagnosis is challenging.  See Key Point 1 for more information about diagnosis. 

There are many subtypes of NHL.  Experts disagree on the actual number but most put it in a range of 10 to 30.  The distinction between types matters.  Each is treated differently and prognosis varies greatly.  Staging is important as well, though less so than type for NHL.  See Key Point 2 for more information about treatment. 

1 National Cancer Institute SEER Cancer Statistics Review
2 Melissa Conrad Stöppler, MD and William C. Shiel Jr., MD, FACP, FACR,
3 Nemours Foundation, Jacksonville, FL
4 The Leukemia & Lymphoma Society

Quick Facts

  • Non-Hodgkin lymphoma (NHL) is one of the fastest rising cancers in the United States (Source:  National Cancer Institute SEER Cancer Statistics Review).  The age-adjusted incidence of NHL rose by 79 percent from 1975 to 2005, an average annual percentage increase of 2.6 percent (Source:  The Leukemia & Lymphoma Society).
  • NHL is the sixth most common cancer among males and the fifth most common cancer among females (Source:  Melissa Conrad Stöppler, MD and William C. Shiel Jr., MD, FACP, FACR,
  • NHL accounts for about 6 percent of childhood cancers (Source:  Nemours Foundation, Jacksonville, FL ).
  • About 66,120 people living in the United States will be diagnosed with non-Hodgkin lymphoma (NHL) in 2008 (Source:  The Leukemia & Lymphoma Society).
  • From 2001-2005, the median age at diagnosis was 67 years of age and the median age at death was 75 years of age for NHL (Source:  National Cancer Institute SEER Cancer Statistics Review).
  • Based on rates from 2003-2005, 2.05% of men and women born today will be diagnosed with NHL at some time during their lifetime (Source:  National Cancer Institute SEER Cancer Statistics Review).
  • NHL disproportionately affects males.  Among the new cases of NHL in 2008, 35,450 will be males and 30,670 females (Source:  The Leukemia & Lymphoma Society).
  • Although blacks, starting in their mid-to-late teens to mid-50s, have higher incidence rates of NHL than whites, whites, beginning at age 60, generally have much higher incidence rates than blacks (Source:  The Leukemia & Lymphoma Society).
  • At least 3,000 of the non-Hodgkin lymphomas each year were associated with AIDS (Source:  National Cancer Institute).
  • NHL is comprised of different subtypes grouped into low grade, intermediate grade, and high grade lymphomas.
  • Survival rates vary widely based on the type of lymphoma and stage of disease at the time of diagnosis. However, according to the American Cancer Society, the overall 5-year relative survival rate for people with non-Hodgkin lymphoma is 63% (though the National Cancer Institute puts it at closer to 67 percent), and 10-year relative survival is 51%.

Ask Your Doctor

This list of questions is a good starting point for discussion with your doctor; however, it is not a comprehensive list.

  • What subtype of non-Hodgkin lymphoma do I have?

  • What is the stage of the cancer? Is there any evidence that the cancer has spread?

  • Can this type of NHL be cured?  What is its typical course?

  • How do I get a second opinion? 

  • What are my treatment choices?  What do you recommend and why?

  • How well has this option worked for others? 

  • What are the implications of not having treatment? 

  • How often will treatment be given and how long will it last? 

  • What are the side effects of the treatment? How can they be managed?

  • Are the possible side effects of this treatment serious enough to interfere with continuing therapy?

  • Will treatment keep me from my normal activities? 

  • What should I do to get ready for treatment?

  • How will we know if the treatment is effective?

  • What can be done if the treatment doesn't work?

  • What is the treatment likely to cost? Will my insurance cover the cost?


Key Point 1

Lymphoma is a cancer of the lymph glands.  Classification tells you what kind you have.  Staging tells you where it is.  Early diagnosis, classification and staging affect treatment and prognosis.

Non-Hodgkin lymphoma (NHL) is a very different cancer than those affecting a specific organ of the body – for example cancer of the prostate or lung.  With NHL a blood cell called a lymphocyte, which normally fights infection, makes too many copies of itself.  Since it's a blood cell it can go anywhere, so we see lymphomas in the blood, in the bone marrow, in lymph nodes, and in organs.  It's also an extremely complicated disease – or more accurately, set of diseases.  There are anywhere from 10 to 30 subtypes of non-Hodgkin lymphoma.  Some are so aggressive that patients are immediately admitted to a hospital for treatment. Others are so indolent (slow progressing) that some patients never require therapy at all.1

non-Hodgkin lymphoma's ability to appear almost anywhere in the body and its complexity make it challenging to diagnose.  Yet, a precise diagnosis is particularly critical for NHL patients to give them the best chance of not being over- or under-treated, and of being cured.   

The process of diagnosis starts in the usual way – with a medical history and physical exam.  The doctor feels the lymph nodes to see if they are swollen and if so, assess the texture of the swelling.  Blood tests are used to rule out infection and other diseases.  Imaging studies range from simple X-rays to CT Scans, MRIs and PET scans. The definitive test for diagnosing NHL is a biopsy. Most often, a surgical biopsy is needed to remove a lymph node.  The tissue is studied by a pathologist and if cancer is present, it will be classified, graded and staged.

Lymphomas can be classified and graded by whether they are: 

  • B- or T-cell lymphomas.  B-cell lymphomas make up most (about 85%) of non-Hodgkin lymphomas in the United States.2  The B- or T-cells are further subdivided bywhether they were derived from immature or mature cells and then by their appearance, genetic make-up, and specific chemical markers.
  • Indolent (slow progressing) or aggressive (fast progressing).
    • Patients with indolent lymphomas can live many years before the disease poses a risk.  They often go into remission for long periods, but they usually relapse.  The majority of the non-Hodgkin lymphomas are indolent.   
    • Aggressive lymphomas are more likely to cause rapid death, but with aggressive treatment they are more likely to be cured than indolent lymphomas.
    • The range from indolent disease to aggressive disease does not fall into discrete categories, but is instead a continuum.3 In general, predicting the outcome for indolent lymphomas is more difficult than for aggressive lymphomas.

The next step is to sort the disease by stage.  The stage of an NHL is determined by the number of tumors and whether they are still localized or have spread beyond the lymph node.  Staging may involve one or more of the following tests:  bone marrow biopsy, CT scan, MRI, ultrasound, spinal tap and PET scan.

The Ann Arbor Staging System is the most popular system for classifying NHL.4

Stage I:

NHL is limited to one lymph node group (e.g., neck, underarm, groin, etc.) above or below the diaphragm, or NHL is in an organ or site other than the lymph nodes (extranodal) but has not spread to other organs or lymph nodes.

Stage II:

NHL is limited to two lymph node groups on the same side of the diaphragm, or NHL is limited to one extranodal organ and has spread to one or more lymph node groups on the same side of the diaphragm.

Stage III:

NHL is in two lymph node groups, with/without partial involvement of an extranodal organ or site above and below the diaphragm.

Stage IV:

NHL is extensive (diffuse) in one organ or site, with/without NHL in distant lymph nodes.

Most NHL is already in Stage III or IV when it's diagnosed.  For some cancers, that would be a bad prognosis. But many non-Hodgkin lymphomas are curable at that stage, depending on the subtype.5

An accurate diagnosis is essential to predict how NHL will progress and to individualize treatment.  Lymphoma responds to very different forms of treatment than other cancers and there are distinct differences in NHL subtypes as well.  

1 Jonathan Friedberg, M.D., University of Rochester Medical Center, on 
2 American Cancer Society
3 Non-Hodgkin's Lymphomas: Making Sense of Diagnosis, Treatment, and Options, by Lorraine Johnston 
5 Dr. John P. Leonard, Weill Cornell Medical College/New York-Presbyterian Hospital, Many Options, but Little Consensus,The New York Times, September 9, 2008

Key Point 2

The treatments for non-Hodgkin lymphoma are effective and improving.  People can live long, productive lives with correct treatment.

Treatment for non-Hodgkin lymphoma has improved significantly in the last decade.  Data from the National Cancer Institute shows that five-year survival rates for the disease jumped from just over 50 percent in the early 1990s to almost 67 percent in 2004.  The Centers for Disease Control (CDC), in a report published in October 2007, says that though the total numbers of cases of non-Hodgkin lymphoma are still rising, the rate of increase has slowed down in the last 10 years.  They further state many more patients are experiencing long-term remissions and even cures – the number of deaths due to non-Hodgkin lymphoma has actually started to fall. 

There is no recipe for treatment success for each subtype of non-Hodgkin lymphoma.  Instead, after doctors zero in on the subtype, growth rate and stage, they work with the patient to formulate a goal of therapy.  Other factors come into play, such as the patient's age and overall health, costs, side effects and quality of life.   

In general, the goal of therapy for a curable form of lymphoma is to aggressively go for the cure, despite the probability of toxicity from treatment in the short term.  The goal for the chronic, indolent forms of lymphoma are more often to control the disease so the patient can live as close to a normal life as possible. 

Watchful waiting may be entirely appropriate for patients if their cancer is slow to progress and they have no symptoms.  This is especially true if the patient is older or has other conditions that are more concerning than the non-Hodgkin lymphoma.   

For those who are treated, chemotherapy (usually combination regimens using several drugs) or a mixture of chemotherapy and radiation is the first line of defense.  Widespread (systemic) disease requires chemotherapy.  Radiation is generally used for early stage, localized non-Hodgkin lymphoma.

Newer biological treatments for people with certain types of non-Hodgkin lymphoma have recently come on the scene.  Rituximab, a monoclonal antibody drug, was approved for use in 1997.  It locks onto lymphoma cells by binding to a protein known as the CD20 antigen on the surface of B-cell tumors.  Because it's so targeted, it produces fewer side effects than standard chemotherapy drugs.  That means doctors can be more aggressive and prescribe this antibody in combination with chemotherapy.  This drug has made a big impact in improving the outcome of patients with lymphoma.  Two newer monoclonal antibody drugs – Bexxar and Zevalin – carry radioactive particles to tumors (called radioimmunotherapy). More new monoclonal antibodies are being developed that go after different targets or that work in different ways.  Monoclonal antibody drugs can be combined with chemotherapy and radiation.   

Stem cell transplantation may be used for advanced and hard-to-treat (refractory) lymphomas as well as for relapse.  They provide a way for doctors to give very high doses of chemotherapy, which kill blood cells and bone marrow and inhibit the body from making new blood cells.  Doctors collect stem cells from the patient or a donor and store them.  After a patient undergoes high-dose chemotherapy, the stem cells are transfused into the bloodstream to replace those that have were damaged or destroyed.

Treatments for non-Hodgkin lymphoma are changing fast.  Doctors have a lot to keep up with.  For that reason, most experts recommend that lymphoma patients make every effort to go to a cancer center with an emphasis on treating NHL.   

Medline Plus

Medline Description: 

Conduct an off-site search for Non-Hodgkin Lymphoma information from MedlinePlus.  These up-to-date search results are based on search terms specific to Second Opinion Key Points.

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