Non-Hodgkin's lymphoma is a cancer of the lymphatic system. The lymphatic system is a network of vessels and glands spread throughout your body.
The lymphatic system is part of your immune system. Clear fluid called lymph flows through the lymphatic vessels and contains infection-fighting white blood cells known as lymphocytes .
In lymphoma, these lymphocytes start to multiply in an abnormal way and begin to collect in certain parts of the lymphatic system, such as the lymph nodes (glands). The affected lymphocytes lose their infection-fighting properties, making you more vulnerable to infection.
The most common symptom of non-Hodgkin's lymphoma is a painless swelling in a lymph node, usually in the neck, armpit or groin. Read more about the symptoms of non-Hodgkin's lymphoma.
How common is it?
About 80% of all lymphomas diagnosed are non-Hodgkin’s lymphoma. In the UK, more than 11,800 cases of non-Hodgkin's lymphoma are diagnosed each year.
Non-Hodgkin's lymphoma is associated with ageing because the chances of developing the condition increase as you get older. The average age at diagnosis is around 65.
What causes it?
The cause of non-Hodgkin's lymphoma is unknown. Risk factors for developing it include:
- having a medical condition that weakens your immune system
- taking immunosuppressant medication
- previous exposure to high doses of radiation or chemicals (including chemotherapy)
- being previously exposed to the Epstein-Barr virus (which causes glandular fever).
Read more about the causes of non-Hodgkin's lymphoma.
Diagnosing non-Hodgkin's lymphoma
The usual way to confirm a diagnosis of non-Hodgkin's lymphoma is by carrying out a biopsy (testing a sample of affected lymph node tissue). Read more about diagnosing non-Hodgkin's lymphoma.
Treatment and outlook
There are many subtypes of non-Hodgkin's lymphoma, but they can generally be put into one of two broad categories:
- high-grade or aggressive non-Hodgkin's lymphoma is where the cancer develops quickly and aggressively
- low-grade or indolent non-Hodgkin's lymphoma is where the cancer develops slowly, and you may not experience any symptoms for many years
Survival rates for non-Hodgkin’s lymphoma vary greatly depending on the exact type, grade and stage of the lymphoma, and the person’s age.
Your recommended treatment plan will take into consideration your general health and age, because many of the treatments have side effects that can be difficult if you have other health problems. Treatments include chemotherapy, radiotherapy and biological therapy. Read more about the treatment of non-Hodgkin's lymphoma.
Although high-grade non-Hodgkin's lymphoma is an aggressive form of cancer, it can be cured with intensive treatment in around 30% of people.
Low-grade non-Hodgkin's lymphoma is not curable for the majority of people. However, there are many effective treatments available and some people can remain well for many years, even without treatment.
Non-Hodgkin's lymphoma symptoms
The most common symptom of non-Hodgkin’s lymphoma is a painless swelling in a lymph node, usually in the neck, armpit or groin.
The swelling is caused by an excess of affected lymphocytes (white blood cells) collecting in your lymph node.
Swollen nodes or glands are a common response to infection, so if you have swollen nodes do not panic; it is highly unlikely they are the result of lymphoma. Read more about lumps and swellings.
Other symptoms will usually only begin once the cancer has spread through most or all of your lymphatic system.
This causes the lymphatic system to stop working properly, which weakens your immune response.
Symptoms of advanced non-Hodgkin's lymphoma include:
- unexplained tiredness or fatigue
- night sweats or fever
- unexplained poor appetite and/or weight loss
- trouble getting rid of infections
- unexplained itching of the skin all over the body
Other symptoms will depend on where in the body the enlarged lymph glands are. For example, if the lymphoma is in the abdomen (tummy), you may have abdominal pain or indigestion.
Non-Hodgkin's lymphoma causes
Lymphoma begins with a change to the structure of DNA in the white blood cells in the lymph. This is known as a genetic mutation.
The DNA gives the cells a basic set of instructions, such as when to grow and reproduce. The mutation in the DNA changes these instructions so that the cells keep growing. This causes them to multiply uncontrollably.
The abnormal lymphocyte cells usually begin to multiply in one or more lymph nodes in a particular area of the body, such as your neck or groin. Over time, it is possible for the abnormal lymphocyte cells to spread into other parts of your body, such as your bone marrow, spleen, liver, skin and lungs.
What triggers lymphoma?
The cause of the initial mutation that triggers lymphoma is unknown. Some experts believe it could be due to a number of related causes.
The known risk factors for developing lymphoma are:
- Having a medical condition that weakens your immune system, such as HIV (this is known as immunosuppression).
- Having medical treatment that weakens your immune system; for example, taking immunosuppressants because you have received an organ transplant.
- Being previously exposed to the Epstein-Barr virus (EBV), which very slightly increases your chance of developing lymphoma. EBV is however a common virus and most healthy people have been infected by this virus in the past, even though they may not remember having had glandular fever.
- Being previously exposed to the Human T-cell lymphotropic virus (HTLV), which slightly increases your chance of developing lymphoma.
- Having a Helicobacter pylori infection, which is a known cause for a type of non-Hodgkin’s lymphoma called MALT lymphoma. H. pylori is a common bacterial infection that usually infects the lining of the stomach and small intestine. Treating the infection can sometimes make this type of lymphoma go away.
- Having received chemotherapy or radiotherapy for an earlier cancer - this slightly increases your risk of developing lymphoma.
- Having coeliac disease (an allergy to gluten that causes inflammation of the small bowel) – this slightly increases your risk of developing non-Hodgkin’s lymphoma. It is more common if you haven't strictly avoided gluten.
Non-Hodgkin's lymphoma is not infectious and is not generally believed to run in families, although there is a slightly higher chance of developing the condition if you have an identical twin with the cancer.
Diagnosing Non-Hodgkin's lymphoma
The presence of swollen lymph nodes and other associated symptoms can suggest a diagnosis of lymphoma, but the only way to confirm the diagnosis is by carrying out a biopsy.
A biopsy involves removing some or all of an affected lymph node, which is then studied in a laboratory. Biopsies can be carried out under a local anaesthetic (where the area is numbed), though there may be some cases where the affected lymph node is not easily accessible and a general anaesthetic may be required (you are put to sleep).
A pathologist (expert in the study of diseased tissue) will then check the tissue sample for the presence of cancerous cells. If they find cancerous cells, they can also identify exactly which type of lymphoma you have, which is an important factor in planning your treatment.
Confirming a diagnosis
There are two main types of lymphocytes (white blood cells found in lymph):
- B-lymphocytes make antibodies that attack infecting bacteria and viruses
- T-lymphocytes kill cells that have been infected with a virus and cause the immune response to respond faster to an infection the second time round
In non-Hodgkin’s lymphoma, either the B-lymphocytes or the T-lymphocytes (or both) can be affected.
Treatment depends on the subtype that you have. There are more than 20 types of non-Hodgkin’s lymphoma, including:
- diffuse large B-cell lymphoma
- follicular lymphoma
- extranodal marginal zone B-cell (MALT)
- mantle cell lymphoma
- Burkitt lymphoma
- mediastinal large B-cell lymphoma
- nodal marginal zone B-cell lymphoma
- small lymphocytic lymphoma
- lymphoplasmacytic lymphoma
- peripheral T-cell lymphoma
- skin (cutaneous) lymphomas
- anaplastic large-cell lymphoma
- lymphoblastic lymphoma (mainly T-cell but can be B-cell)
B-cell lymphomas are more common than T-cell lymphomas.
See the Macmillan cancer website for more information on the different kinds of non-Hodgkin’s lymphoma.
If a biopsy reveals the presence of non-Hodgkin's lymphoma, further testing will be required to check how far the lymphoma has spread. This allows a doctor to diagnose the stage of your lymphoma.
Further tests may include:
- Blood tests – samples of blood will be taken throughout your diagnosis and treatment to check your general health, the levels of red and white cells and platelets in your blood, and how well organs, such as your liver and kidney, are working.
- Bone marrow sample – another biopsy may be carried out to see if the lymphoma has spread to your bone marrow. This involves using a long needle to remove a sample of bone marrow from your pelvis and can be done using a local anaesthetic.
- Chest X-ray – can check whether your lymphoma has spread to your chest or lungs.
- Computerised tomography (CT) scan – takes a series of X-rays that build up a three-dimensional picture of the inside of the body to check the spread of your lymphoma.
- Magnetic resonance imaging (MRI) scan – uses strong magnetic fields instead of X-rays to build up a detailed picture of areas of your body to check the spread of your lymphoma.
- Positron emission tomography (PET) scan – a type of scan that shows how the tissues of the body are working by measuring the activity of cells in different parts of the body. It can check the spread of your lymphoma and the impact of treatment.
- Lumbar puncture – using a thin needle, a sample of spinal fluid is taken and examined to see if it contains any lymphoma cells.
Staging of lymphoma
When the testing is complete, it should be possible to determine the stage of your lymphoma. These stages are explained below.
- stage 1 (or I): the lymphoma is limited to one group of lymph nodes, such as your neck or groin nodes either above or below your diaphragm
- stage 2 (or II): two lymph node groups are affected, either above or below the diaphragm
- stage 3 (or III): the lymphoma has now spread to lymph node groups above and below the diaphragm
- stage 4 (or IV): the lymphoma has spread through the lymphatic system and is now present in organs and/or bone marrow outside of the lymphatic system
Health professionals also use an additional grading system, either 'a' or 'b':
- a-type lymphoma means that you have no additional symptoms other than swollen lymph nodes
- b-type lymphoma means that you have additional symptoms, such as weight loss, fever or night sweats
Non-Hodgkin's lymphoma treatment
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.
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
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.
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.
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.
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 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:
- loss of appetite
- mouth ulcers
- 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.
Read more about chemotherapy.
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:
- 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 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
- 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:
- fever and/or chills
- 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 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
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
Read more about treating non-Hodgkin's lymphoma and living with non-Hodgkin's 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 doctor 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:
- aching muscles
- a painful blistering rash
You should also make sure that all of your vaccinations are up to date. Your doctor or care team will advise you on this.
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 doctor.
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 doctor at an early stage.