Non-Hodgkins Lymphoma Causes, Symptoms, Diagnosis, Treatment, Prevention

Non-Hodgkins Lymphoma Causes, Symptoms, Diagnosis, Treatment, Prevention


What Is Non-Hodgkin's Lymphoma?


Non-Hodgkin's lymphoma is a type of cancer. Lymphoma is a general term for cancers that develop in the lymphatic system. Hodgkin's disease is one type of lymphoma. All other lymphomas are grouped together and are called non-Hodgkin's lymphoma. Lymphomas account for about 5 percent of all cases of cancer in this country.

The lymphatic system is part of the body's immune system. It helps the body fight disease and infection. The lymphatic system includes a network of thin tubes that branch, like blood vessels, into tissues throughout the body. Lymphatic vessels carry lymph, a colorless, watery fluid that contains infection-fighting cells called lymphocytes. Along this network of vessels are small organs called lymph nodes. Clusters of lymph nodes are found in the underarms, groin, neck, chest, and abdomen. Other parts of the lymphatic system are the spleen, thymus, tonsils, and bone marrow. Lymphatic tissue is also found in other parts of the body, including the stomach, intestines, and skin.

Cancer is a group of many related diseases that begin in cells, the body's basic unit of life. To understand non-Hodgkin's lymphoma, it is helpful to know about normal cells and what happens when they become cancerous. The body is made up of many types of cells. Normally, cells grow and divide to produce more cells only when the body needs them. This orderly process helps keep the body healthy. Sometimes cells keep dividing when new cells are not needed, creating a mass of extra tissue. This mass is called a growth or tumor. Tumors can be either benign (not cancerous) or malignant (cancerous).

In non-Hodgkin's lymphoma, cells in the lymphatic system become abnormal. They divide and grow without any order or control, or old cells do not die as cells normally do. Because lymphatic tissue is present in many parts of the body, non-Hodgkin's lymphoma can start almost anywhere in the body. Non-Hodgkin's lymphoma may occur in a single lymph node, a group of lymph nodes, or in another organ. This type of cancer can spread to almost any part of the body, including the liver, bone marrow, and spleen.

What causes non-Hodgkin's lymphoma?


We don't know what causes non-Hodgkin's lymphoma (NHL). NHL occurs when your body produces too many abnormal lymphocytes. In the normal life cycle of lymphocytes (a type of white blood cell), old lymphocytes die and your body creates new ones to replenish the supply. In NHL, lymphocytes grow indefinitely, so the number of circulating lymphocytes increases, filling up the lymph nodes and causing them to swell.

In NHL, either B cells or T cells are involved in this process. These are the two subtypes of lymphocytes.

B cells produce antibodies that fight infections. This is the most common type of cell involved in NHL.

T cells kill the foreign substances directly. NHL less frequently originates from T cells.

The following are some of the common subtypes of NHL:

Burkitt's lymphoma:


This lymphoma has two major subtypes, an African type closely associated with an infection with the Epstein-Barr virus and the non-African, or sporadic, form that is not linked to the virus.

Diffuse large cell lymphoma


This represents the most common lymphoma (approximately 30% of NHL) and can be rapidly fatal if not treated.

Follicular lymphoma


These lymphomas exhibit a specific growth pattern when viewed under the microscope (follicular or nodular pattern); they are usually advanced at the time of diagnosis.

MALT lymphoma


This is a B cell lymphoma that usually affects individuals in their 60s. The most common area for this lymphoma to develop is the stomach.

Mantle cell lymphoma


One of the rarest of the NHL, mantle cell lymphoma accounts for about 6% of cases. This NHL is difficult to treat and is a subtype of B cell lymphoma.

Adult T cell lymphoma/leukemia


This is a rare but aggressive NHL of the immune system's T cells. Human T cell leukemia/lymphotropic virus type (HTLV-1) is believed to be the cause.

Risk factors of Non-Hodgkins Lymphoma


In most cases, people diagnosed with non-Hodgkin's lymphoma don't have any obvious risk factors, and many people who have risk factors for the disease never develop it. Some factors that may increase the risk of non-Hodgkin's lymphoma include:

Medications that suppress your immune system


If you've had an organ transplant, you're more susceptible because immunosuppressive therapy has reduced your body's ability to fight off new illnesses.

Infection with certain viruses and bacteria


Certain viral and bacterial infections appear to increase the risk of non-Hodgkin's lymphoma. Viruses linked to increased non-Hodgkin's lymphoma risk include HIV and Epstein-Barr virus. Bacteria linked to an increased risk of non-Hodgkin's lymphoma include the ulcer-causing Helicobacter pylori.

Chemicals


Certain chemicals, such as those used to kill insects and weeds, may increase your risk of developing non-Hodgkin's lymphoma. More research is needed to understand the possible link between pesticides and the development of non-Hodgkin's lymphoma.

Older age


Non-Hodgkin's lymphoma can occur at any age, but the risk increases with age. It's most common in people in their 60s or older.

Symptoms of Non-Hodgkins Lymphoma


The most common symptom of non-Hodgkin's lymphoma is a painless swelling of the lymph nodes in the neck, underarm, or groin.

Other symptoms may include the following:

  • Unexplained fever
  • Night sweats
  • Constant fatigue
  • Unexplained weight loss
  • Itchy skin
  • Reddened patches on the skin

When symptoms like these occur, they are not sure signs of non-Hodgkin's lymphoma. They may also be caused by other, less serious conditions, such as the flu or other infections. Only a doctor can make a diagnosis. When symptoms are present, it is important to see a doctor so that any illness can be diagnosed and treated as early as possible. Do not wait to feel pain; early non-Hodgkin's lymphoma may not cause pain.

Diagnosis of Non-Hodgkins Lymphoma


If non-Hodgkin's lymphoma is suspected, the doctor asks about the person's medical history and performs a physical exam. The exam includes feeling to see if the lymph nodes in the neck, underarm, or groin are enlarged. In addition to checking general signs of health, the doctor may perform blood tests.

The doctor may also order tests that produce pictures of the inside of the body. These may include:

  • X-rays: Pictures of areas inside the body created by high-energy radiation.
  • CT (or CAT) scan: A series of detailed pictures of areas inside the body. The pictures are created by a computer linked to an x-ray machine.
  • MRI (magnetic resonance imaging): Detailed pictures of areas inside the body produced with a powerful magnet linked to a computer.
  • Lymphangiogram: Pictures of the lymphatic system taken with x-rays after a special dye is injected to outline the lymph nodes and vessels.

A biopsy is needed to make a diagnosis. A surgeon removes a sample of tissue so that a pathologist can examine it under a microscope to check for cancer cells. A biopsy for non-Hodgkin's lymphoma is usually taken from a lymph node, but other tissues may be sampled as well. Sometimes, an operation called a laparotomy may be performed. During this operation, a surgeon cuts into the abdomen and removes samples of tissue to be checked under a microscope.

A patient who needs a biopsy may want to ask the doctor some of the following questions:

  • Why do I need to have a biopsy?
  • How long will the biopsy take? Will it hurt?
  • How soon will I know the results?
  • If I do have cancer, who will talk with me about treatment? When?

What is the treatment for non-Hodgkin's lymphoma?


Some people may not need treatment straight away for their non-Hodgkin’s lymphoma.

If the initial cancer was very small and removed by the biopsy, no further treatment may be needed.

Wait-and-see approach


If the disease is low grade and not at advanced stage, a period of "watchful waiting" is often recommmended as some patients may take many years to get troublesome symptoms from their disease.
If watchful waiting is recommended, you will be seen regularly in clinic for review and invited to come back at any stage if you feel your symptoms are worse.

Explaining treatment terms 


Remission

When treatment of lymphoma is started, the aim is to achieve a remission. The best remission is a ‘complete’ remission (when the disease can no longer be detected). Remission is called ‘partial’ where the diseased glands have been made much smaller.

Refractory and relapsed lymphoma

Sometimes, the lymphoma does not get better with initial treatment - this is called 'refractory' lymphoma.
'Relapsed' lymphoma means that the disease has come back after it initially responded to treatment.
Both refractory and relapsed lymphoma can often be successfully improved or sometimes cured with a different treatment approach.

Cure

At least half of all people who initially respond to treatment for non-Hodgkin’s lymphoma will suffer a relapse of their disease. For this reason, people are only said to have been cured of lymphoma when there is no further evidence of their disease after a period of observation (usually five years).

Sometimes, usually when you have a lymphoma that is likely to relapse, your doctor will recommend a stem cell transplant after initial treatment has controlled the disease.

Treatment plan


The recommended treatment plan will depend on your general health and age, because some of the treatments can cause serious side effects and complications, which can put a tremendous strain on the body.

Nowadays, it is normal practice for your treatment plan to be discussed by several doctors and other health professionals who specialise in different aspects of treating lymphoma (see box, right).

This group of people, known as the 'multidisciplinary team', meet regularly (at least once a week). They check that your diagnosis and staging is correct and that you are getting the best available treatment. Your personal wishes for treatment will always be taken into consideration in this discussion.

There are several factors to take into account when deciding on your treatment. These include:
  • your age and general health
  • your symptoms
  • the likely progression of your lymphoma
  • specific subtype of your lymphoma
  • the stage of your lymphoma
  • possible side effects of treatment
Your doctor will recommend the best treatment options to you. They may also offer you the opportunity to participate in a clinical trial. Unless your health is immediately threatened by the lymphoma, it is better not to rush into making a decision about your treatment plan.

Before deciding, you will be encouraged to talk to friends, family and your partner (if you have one). You will also be invited back to see your care team for a full review and discussion about the risks and benefits of any treatment planned for you before you actually start.

Chemotherapy


Chemotherapy is widely used treatment for lymphoma, either on its own, combined with biological therapy and/or combined with radiotherapy.

Some chemotherapy is given by injection (intravenous chemotherapy) and some is given by mouth (oral chemotherapy).

The type of chemotherapy you receive will depend on the type and stage of your non-Hodgkin's lymphoma.
If it is thought that your lymphoma is curable, you will normally receive an aggressive treatment programme of chemotherapy (with or without radiotherapy) designed to kill all of the cancerous cells in your body. However, if a cure is unlikely, a more moderate treatment programme may be used, which can often provide long-term relief from symptoms.

Chemotherapy is usually given over a period of a few months on an outpatient basis, meaning you should not have to stay in hospital overnight. However, there may be times when your symptoms or the side effects of treatment become particularly troublesome, and a longer hospital stay may be needed.

When you start treatment, you will be given a '24-hour hotline' number to call so that any problems relating to your treatment can be addressed as soon as possible.

Chemotherapy kills the cancerous cells but it can also damage healthy cells, which can lead to a number of common side effects. These include:
  • nausea
  • vomiting
  • diarrhoea
  • loss of appetite
  • mouth ulcers
  • tiredness
  • skin rashes
  • hair loss
  • infertility – this may be temporary or permanent
Side effects should pass once treatment has finished. You must tell your care team if side effects become particularly troublesome, as there are medicines that can help you cope better with some side effects. For example, creams and gels can treat mouth ulcers.

Aggressive chemotherapy can also affect your bone marrow. This can interfere with the production of healthy blood cells, which can lead to the following symptoms:
  • fatigue
  • breathlessness
  • increased vulnerability to infection
  • bleeding and bruising more easily
Treatment may need to be delayed so that you can produce more healthy blood cells. Growth factor medicines can also stimulate the production of blood cells.

Radiotherapy


Radiotherapy is often used to treat stage 1 and 2 lymphomas, when the cancer cells are in only one part of the body. Treatment is normally given daily, monday to friday, over the space of two to six weeks. You should not have to stay in hospital between appointments.

The radiographer will need to first carefully plan your treatment. This may involve one or several appointments. The radiographer uses a machine to 'map' out the lymphoma and decide what parts of your body the radiotherapy should be directed at. This planning may involve making small tattoo marks on your skin or making a special cast to ensure that you are kept in exactly the same position for treatment as you were for planning.

Radiotherapy itself is painless, but it has a number of common side effects. These can vary, depending on which part of your body is being treated. For example, if the affected lymph nodes are in your throat, radiotherapy can lead to a sore throat, while treatment to the head can lead to hair loss.

Other common side effects include:
  • tkin rash
  • tiredness
  • nausea
  • vomiting
  • dry mouth
  • loss of appetite

Monoclonal antibody (biological) therapy


The human immune system is very clever. When you get an infection, your immune system will develop systems to stop you getting the same infection again.

One of the ways your immune system does this is to produce proteins called antibodies that recognise the specific features (antigens) of the infection. If you do get exposed to the same infection again in the future, these antibodies will bind to the antigens and your immune system will destroy the antibody-antigen complex.
Scientists recognised how important this immune reaction was and have genetically engineered antibodies that can target antigens on lymphoma cells. These antibodies are called ‘monoclonal’ antibodies, because they specifically recognize one particular antigen. 

Monoclonal antibody therapy can be used to treat some types of non-Hodgkin’s lymphoma. It is often given in combination with chemotherapy to make the treatment more potent.

The  first type of monoclonal antibody therapy used to treat non-Hodgkin’s lymphoma has been a medicine called rituximab. Rituximab is an artificially made antibody that specifically recognises the CD20 antigen found on the surface of B lymphocytes. It may therefore be useful in people who have B-cell non-Hodgkin's lymphoma (eithe high grade or low grade).

Rituximab is administered directly into your vein over the course of a few hours. It is common to experience flu-like symptoms when you are being treated with rituximab. Possible symptoms include:
  • headache
  • fever and/or chills
  • fatigue
  • muscle pain
You will be given additional medication to prevent or lessen these side effects. Side effects should improve over time as your body gets used to rituximab.

Rituximab was the first monoclonal antibody therapy to be produced for the treatment of non-Hodgkin’s lymphoma and it remains the most important. Because it has been so successful, scientists are working hard to make more monoclonal antibody treatments for lymphoma and some of these are already at an advanced stage in clinical trials. You may be asked to participate in one of these.

Steroids


Steroids are commonly used in combination with chemotherapy to treat non-Hodgkin's lymphoma. Research has shown that using steroids makes the chemotherapy more effective.

Steroids are normally given by mouth, usually at the same time as your chemotherapy. A short-term course of steroids, lasting no more than a few months, is usually recommended as this limits the number of side effects you could have. Common side effects of short-term steroid use include:
  • increased appetite
  • altered mood
  • problems sleeping
  • indigestion
On rare occasions, you may have to take steroids on a long-term basis. Side effects of long-term steroid use include:
  • swelling in your hands, feet and eyelids
  • weight gain
  • raised blood pressure
  • an increased risk of developing diabetes
  • altered vision
  • a slightly higher risk of developing infections

Additional aspects of cancer treatments


In addition to medical therapies, patients will also require supportive care. You should have the opportunity to learn about your disease and the treatment options and discuss this with your care team. Most cancer centers will have support groups where you can share your concerns with other patients and learn from their experiences.

Some patients find moderate physical activity helpful. You should discuss with your doctor what kind of activities are appropriate.

Eating the appropriate amounts of foods, as well as the right foods, is an important part of your treatment. Speaking with a nutritionist can be very helpful.

In addition, vitamin deficiencies (especially vitamin D) have recently been linked to worse survival in some subgroups of cancer patients. Patients should discuss their nutritional requirements with their health-care team.

Appropriate caloric intake is important especially if nausea is present as a result of your treatments. Some people find that exercise can help their nausea during therapy. Acupuncture has also shown to decrease the side effects of cancer treatments.

Preparing for Non-Hodgkins Lymphoma Treatment


Many people with cancer want to learn all they can about their disease and their treatment choices so they can take an active part in decisions about their medical care. When a person is diagnosed with cancer, shock and stress are natural reactions. These feelings may make it difficult for people to think of everything they want to ask the doctor. Often, it helps to make a list of questions. To help remember what the doctor says, patients may take notes or ask whether they may use a tape recorder. Some people also want to have a family member or friend with them when they talk to the doctor -- to take part in the discussion, to take notes, or just to listen.

These are some questions a patient may want to ask the doctor before treatment begins:

  • What kind of non-Hodgkin's lymphoma do I have?
  • What is the stage of the disease?
  • What are my treatment choices? Which do you recommend for me? Why?
  • What are the risks and possible side effects of each treatment?
  • What side effects should I report to you?
  • How long will treatment last?
  • What are the chances that the treatment will be successful?
  • Will treatment affect my normal activities? If so, for how long?
  • Are new treatments under study? Would a clinical trial be appropriate for me?
  • What is the treatment likely to cost?

Patients do not need to ask all their questions or remember all the answers at one time. They will have other chances to ask the doctor to explain things and to get more information.

How to Prevent Non-Hodgkin's Lymphoma? Can non-Hodgkin lymphoma be prevented?


Since the cause of Adult Non-Hodgkin's Lymphoma is unknown, there are few things you can do to reduce your risk. Some possible means to reduce risk are explained here.

Avoid Repeated Exposure to Certain Chemicals


People who work around pesticides, fertilizers, and solvents have a greater chance of developing non-Hodgkin's lymphoma than people who are not exposed to these chemicals.

Avoid Exposure to Radiation


Lymphomas are more common in groups of individuals who have unusually high exposure to radiation, such as people exposed from bomb blasts and those exposed to high levels of radon gas. Therapeutic x-rays do not increase your risk of developing lymphoma.

Avoid Exposure to HIV


Non-Hodgkin's lymphoma occurs more often in people who have been infected with the HIV and AIDS than in those who are HIV-negative. Steps to avoid HIV infection include:

1. Take precautions when engaging in sexual activity:
  • Abstain from sex or have only monogamous sex with a person who is not infected with HIV.
  • Use a latex condoms and water-based lubricants.
  • Use a female polyurethane condom.
  • Limit your number of sexual partners.
  • Avoid sexual partners who are HIV-positive or use injected drugs.
2. Do not share hypodermic needles with anyone.

Control Auto-immune Diseases


There is some evidence to suggest that patients who have chromic immune-mediated disease, such as gluten intolerance, are more likely to develop lymphomas than the general population. Although the evidence is incomplete, it's a good idea to follow your doctor's recommendations for managing your immune-mediated illness to avoid any possible increase of risk in developing lymphoma.

Complications of non-Hodgkin's lymphoma 


Being immunocompromised (having a weakened immune system) is a common complication of lymphoma treatment. Even if your lymphatic system is restored to normal, many of the medications that treat non-Hodgkin's lymphoma weaken your immune system.

This means you are more vulnerable to infections, and there is an increased risk of developing serious complications from infections. You may be advised to take regular doses of antibiotics to prevent infections occurring in the early stages after treatment. Your immune system will usually recover in the months and years after treatment.

If you think you might have an infection, you must report any symptoms to your care team or GP immediately because prompt treatment may be needed to prevent serious complications. This is particularly important in the first few months after treatment.

Symptoms of infection include:
  1. fever
  2. headache
  3. aching muscles
  4. diarrhoea
  5. tiredness
  6. a painful blistering rash
You should also make sure that all of your vaccinations are up to date. Your GP or care team will advise you on this.

Infertility


Many of the treatments for lymphoma can cause infertility. Infertility is often temporary, but in some cases it may be a permanent side effect.

People who are particularly at risk of becoming infertile are those who have received very high doses of chemotherapy and radiotherapy. Your care team will estimate the risk of infertility in your specific circumstances.

It is sometimes possible to guard against any risk of infertility before beginning treatment. For example, men can store samples of their sperm, and women can occasionally store their eggs, which can be fertilised and placed back into the womb after treatment.

Use of contraception is strongly recommended during chemotherapy and for one year afterwards as chemotherapy can damage a new embryo (baby).

Other health issues


Treatment for lymphoma can increase your risk of getting conditions such as heart disease, lung disease, kidney disease, thyroid disease, diabetes and cataracts at a younger age than normal. Having a diagnosis of cancer can also increase your risk of suffering from depression. These conditions can all be effectively managed if you report unusual symptoms to your GP.

Secondary cancers


Unfortunatedly people who have had one cancer are more likely to get a second cancer, which may be the same or different to their first cancer. Chemotherapy and radiotherapy further increase this risk.

This risk will have been considered carefully when your initial treatment was planned – it is one of the reasons why a period of 'watchful waiting' is recommended for many people with low-grade non-Hodgkin’s lymphoma.

You can help yourself to avoid getting a second cancer by adopting a healthy lifestyle (not smoking, maintaining a healthy weight with a balanced diet, taking regular exercise). You should also report any symptoms that might suggest another cancer to your GP at an early stage.

Recovery and Outlook


It is natural for anyone facing cancer to be concerned about what the future holds. Understanding the nature of cancer and what to expect can help patients and their loved ones plan treatment, anticipate lifestyle changes, and make quality of life and financial decisions.

Cancer patients frequently ask their doctors or search on their own for an answer to the question, "What is my prognosis?" Prognosis is a prediction of the future course and outcome of a disease and an indication of the likelihood of recovery. However, it is only an estimate. When doctors discuss a patient's prognosis, they are attempting to project what is likely to occur for that individual patient.

Sometimes patients use statistics to try to figure out their chances of being cured. However, statistics reflect the experience of a large group of patients and cannot be used to predict what will happen to a particular patient because no two patients are alike. The prognosis for a person with non-Hodgkin's lymphoma can be affected by many factors, particularly the type and stage of the cancer and the patient's age, general health, and response to treatment. The doctor who is most familiar with a patient's situation is in the best position to help interpret statistics and discuss that person's prognosis.

When doctors talk about surviving cancer, they may use the term remission rather than cure. Although many people with non-Hodgkin's lymphoma are successfully treated, doctors use the term remission because cancer can return. It is important to discuss the possibility of recurrence with the doctor.

Nutrition During Cancer Treatment


Eating well during cancer treatment means getting enough calories and protein to help prevent weight loss and regain strength. Good nutrition often helps people feel better and have more energy.

Some people with cancer find it hard to eat a balanced diet because they may lose their appetite. In addition, common side effects of treatment, such as nausea, vomiting, or mouth sores, can make eating difficult. Often, foods taste different. Also, people being treated for cancer may not feel like eating when they are uncomfortable or tired.

Doctors, nurses, and dietitians can offer advice on how to get enough calories and protein during cancer treatment.

Followup Care


People who have had non-Hodgkin's lymphoma should have regular followup examinations after their treatment is over. Followup care is an important part of the overall treatment plan, and people should not hesitate to discuss it with their health care provider. Regular followup care ensures that patients are carefully monitored, any changes in health are discussed, and new or recurrent cancer can be detected and treated as soon as possible. Between followup appointments, people who have had non-Hodgkin's lymphoma should report any health problems as soon as they appear.

Support for People with Cancer


Living with a serious disease is not easy. People with cancer and those who care about them face many problems and challenges. Coping with these problems is often easier when people have helpful information and support services.

Friends and relatives can be very supportive. Also, it helps many patients to discuss their concerns with others who have cancer. Cancer patients often get together in support groups, where they can share what they have learned about coping with cancer and the effects of treatment. It is important to keep in mind, however, that each person is different. Treatments and ways of dealing with cancer that work for one person may not be right for another -- even if they both have the same kind of cancer. It is always a good idea to discuss the advice of friends and family members with the health care provider.

People living with cancer may worry about what the future holds. They may worry about holding their jobs, caring for their families, keeping up with daily activities, or personal relationships. Concerns about tests, treatments, hospital stays, and medical bills are also common. Doctors, nurses, and other members of the health care team can answer questions about treatment, working, or other activities. Meeting with a social worker, counselor, psychologist, or member of the clergy can be helpful to people who want to talk about their feelings or discuss their concerns. Often, a social worker can suggest groups that can help with rehabilitation, emotional support, financial aid, transportation, or home care.