Introduction

Non-Hodgkin lymphoma is an uncommon cancer that develops in the lymphatic system, which 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 non-Hodgkin lymphoma, the affected 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 lymphoma is a painless swelling in a lymph node, usually in the neck, armpit or groin.

Read more about the symptoms of non-Hodgkin lymphoma

Who's affected?

In the UK, more than 12,000 people are diagnosed with non-Hodgkin lymphoma each year.

Non-Hodgkin lymphoma can occur at any age, but your chances of developing the condition increase as you get older, with most cases diagnosed in people over 65. Slightly more men than women are affected.

What causes non-Hodgkin lymphoma?

The exact cause of non-Hodgkin lymphoma is unknown. However, your risk of developing the condition is increased if:

  • you have a medical condition that weakens your immune system
  • you take immunosuppressant medication
  • you've previously been exposed to a common virus called the Epstein-Barr virus – which causes glandular fever

You also have a slightly increased risk of developing non-Hodgkin lymphoma if a first-degree relative (such as a parent or sibling) has had the condition.

Read more about the causes of non-Hodgkin lymphoma.

How non-Hodgkin lymphoma is diagnosed

The only way to confirm a diagnosis of non-Hodgkin lymphoma is by carrying out a biopsy.

This is a minor surgical procedure where a sample of affected lymph node tissue is removed and studied in a laboratory.

Read more about diagnosing non-Hodgkin lymphoma.

Treatment and outlook

There are many subtypes of non-Hodgkin lymphoma, but they can generally be put into one of two broad categories:

  • high-grade or aggressive non-Hodgkin lymphoma – where the cancer develops quickly and aggressively
  • low-grade or indolent non-Hodgkin lymphoma – where the cancer develops slowly, and you may not experience any symptoms for many years

The outlook for non-Hodgkin lymphoma varies greatly, depending on the exact type, grade and extent of the lymphoma, and the person’s age.

Low-grade tumours don't necessarily require immediate medical treatment, but are harder to completely cure. High-grade lymphomas need to be treated straight away, but tend to respond much better to treatment and can often be cured. 

The main treatments used for non-Hodgkin lymphoma are:

Overall, most cases of non-Hodgkin lymphoma are considered very treatable. You can read more detailed information about the outlook for non-Hodgkin lymphoma on the Cancer Research UK website.

However, there's a risk of long-term problems after treatment, including infertility and an increased risk of developing another type of cancer in the future.

Read more about: 

Information about you

If you have non-Hodgkin lymphoma, your clinical team will pass information about you on to the National Congenital Anomaly and Rare Diseases Registration Service (NCARDRS).

This helps scientists look for better ways to prevent and treat this condition. You can opt out of the register at any time.

Find out more about the register.

Symptoms

The most common symptom of non-Hodgkin lymphoma is a painless swelling in a lymph node, usually in the neck, armpit or groin.

Lymph nodes, also known as lymph glands, are pea-sized lumps of tissue found throughout the body. They contain white blood cells that help to fight against infection.

The swelling is caused by a certain type of white blood cell, known as lymphocytes, collecting in the lymph node.

However, it's highly unlikely you have non-Hodgkin lymphoma if you have swollen lymph nodes, as these glands often swell as a response to infection.

Other symptoms

Some people with non-Hodgkin lymphoma also have other more general symptoms. These can include:

  • night sweats
  • unintentional weight loss 
  • a high temperature (fever)
  • a persistent cough or feeling of breathlessness
  • persistent itching of the skin all over the body

Other symptoms depend on where in the body the enlarged lymph glands are. For example, if the abdomen (tummy) is affected, you may have abdominal pain or indigestion.

A few people with lymphoma have abnormal cells in their bone marrow when they're diagnosed. This may lead to:

  • persistent tiredness or fatigue
  • an increased risk of infections
  • excessive bleeding – such as nosebleeds, heavy periods and spots of blood under the skin

When to seek medical advice

See your GP if you have any of the above symptoms, particularly if you have persistently swollen glands with no other signs of infection.

While the symptoms are unlikely to be caused by non-Hodgkin lymphoma, it's best to get them checked out.

Causes

Non-Hodgkin lymphoma is caused by a change (mutation) in the DNA of a type of white blood cell called lymphocytes, although the exact reason why this happens isn't known.

DNA gives cells a basic set of instructions, such as when to grow and reproduce. The mutation in the DNA changes these instructions, so the cells keep growing. This causes them to multiply uncontrollably.

The abnormal lymphocytes 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's possible for the abnormal lymphocytes to spread into other parts of your body, such as your:

  • bone marrow
  • spleen
  • liver
  • skin
  • lungs

However, in some cases, non-Hodgkin lymphoma first develops in an organ or somewhere else outside the lymphatic system (the network of lymph vessels and glands found throughout the body).

Who's most at risk?

While the cause of the initial mutation that triggers non-Hodgkin lymphoma is unknown, a number of factors can increase your risk of developing the condition. These include:

  • having a medical condition that weakens your immune system, such as HIV
  • having medical treatment that weakens your immune system – for example, taking medication to suppress your immune system after an organ transplant
  • having an autoimmune condition (a condition caused by problems with the immune system), such as rheumatoid arthritis, lupus or Sjogren's syndrome
  • being previously exposed to the Epstein-Barr virus – a common virus that causes glandular fever
  • being previously exposed to the Human T-cell lymphotropic virus (HTLV)
  • having a Helicobacter pylori infection – a common bacterial infection that usually infects the lining of the stomach and small intestine
  • having received chemotherapy or radiotherapy for an earlier cancer
  • having coeliac disease – an adverse reaction to gluten that causes inflammation of the small bowel

Non-Hodgkin lymphoma isn't infectious and isn't thought to run in families, although your risk may be slightly increased if a first-degree relative (such as a parent or sibling) has had lymphoma.

Non-Hodgkin lymphoma can occur at any age, but most cases are diagnosed in people over 65. The condition is slightly more common in men than women.

Diagnosis

If you see your GP because you're concerned about symptoms of non-Hodgkin lymphoma, they'll ask about your health and carry out a simple physical examination.

If necessary, your GP will refer you to hospital for further tests.

In 2015, the National Institute for Health and Care Excellence (NICE) published guidelines to help GPs recognise the signs and symptoms of non-Hodgkin lymphoma and refer people for the right tests faster.

To find out if you should be referred for further tests for suspected non-Hodgkin lymphoma, read the NICE 2015 guidelines on Suspected Cancer: Recognition and Referral.

If you're referred to hospital, a biopsy will usually be carried out, as this is the only way to confirm a diagnosis of non-Hodgkin lymphoma.

Biopsy

A biopsy involves removing some or all of an affected lymph node, which is then studied in a laboratory.

Biopsies are small operations that can often be carried out under a local anaesthetic (where the area is numbed). In some cases, the affected lymph node isn't easily accessible and a general anaesthetic may be required (where you're asleep).

A pathologist (an 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 non-Hodgkin lymphoma you have, which is an important factor in planning your treatment.

Types of non-Hodgkin lymphoma

There are more than 30 types of non-Hodgkin 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

The Macmillan Cancer Support website has more detailed information on the different types of non-Hodgkin lymphoma.

Further testing

If a biopsy confirms a diagnosis of non-Hodgkin 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 (see below).

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 – this can check whether the cancer has spread to your chest or lungs
  • computerised tomography (CT) scan – this scan takes a series of X-rays that build up a 3D picture of the inside of the body to check the spread of the cancer 
  • magnetic resonance imaging (MRI) scan – this scan uses strong magnetic fields to build up a detailed picture of areas of your body to check the spread of the cancer
  • positron emission tomography (PET) scan – this scan measures the activity of cells in different parts of the body and can check the spread of the cancer and the impact of treatment; it's usually taken at the same time as a CT scan to show precisely how the tissues of different sites of the body are working
  • lumbar puncture – using a thin needle, a sample of spinal fluid is taken and examined to see if it contains any lymphoma cells

Stages of non-Hodgkin lymphoma

When the testing is complete, it should be possible to determine the stage of your lymphoma. "Staging" means scoring the cancer by how far it's spread.

The main stages of non-Hodgkin lymphoma are.

  • stage 1 – the cancer is limited to one group of lymph nodes, such as your neck or groin nodes either above or below your diaphragm (the sheet of muscle underneath the lungs)
  • stage 2 – two or more lymph node groups are affected, either above or below the diaphragm
  • stage 3 – the cancer has spread to lymph node groups above and below the diaphragm
  • stage 4 – the lymphoma has spread through the lymphatic system and is now present in organs or bone marrow

Health professionals also add the letter "A" or "B" to your stage to indicate whether or not you have certain symptoms.

"A" is put after your stage if you have no additional symptoms other than swollen lymph nodes. "B" is put after your stage if you have additional symptoms of weight loss, fever or night sweats.

In some cases, health professionals also use additional letters to indicate where the cancer first developed. For example, "E" (extranodal) means the cancer developed outside the lymphatic system.

Grading non-Hodgkin lymphoma

Testing can also help health professionals decide the "grade" of the cancer. There are two main grades of non-Hodgkin lymphoma:

  • low-grade or indolent non-Hodgkin lymphoma is where the cancer develops slowly, and you may not experience any symptoms for many years
  • high-grade or aggressive non-Hodgkin lymphoma is where the cancer develops quickly and aggressively

Low-grade tumours don't necessarily require immediate medical treatment, but are harder to completely cure. High-grade lymphomas need to be treated immediately, but tend to respond much better to treatment and can often be cured.

In some cases, low-grade lymphomas can develop into high-grade lymphomas over time.

Read more about treating non-Hodgkin lymphoma.

Treatment

Non-Hodgkin lymphoma is usually treated with cancer-killing medication or radiotherapy, although some people may not need treatment straight away.

In a few cases, if the initial cancer is very small and can be removed during a biopsy, no further treatment may be needed.

Your treatment plan

The recommended treatment plan will depend on your general health and age, as many of the treatments can put a tremendous strain on the body.

Discussions about your treatment plan will usually take place with several doctors and other health professionals who specialise in different aspects of treating lymphoma. This is known as a multidisciplinary team (MDT).

Your MDT will recommend the best treatment options for you. However, you shouldn't be rushed into making a decision about your treatment plan. Before deciding, you may wish to talk to friends, family and your partner.

You'll be invited back to see your care team for a full discussion about the risks and benefits of any treatments planned before treatment begins.

You can ask your care team if a clinical trial is available to take part in.

The main treatment options for non-Hodgkin lymphoma are described below.

Wait-and-see approach

If the disease is low-grade (slow developing) and you're well, a period of "watchful waiting" is often recommended. This is because some people take many years to develop troublesome symptoms and starting treatment immediately is often felt to be unnecessary.

If watchful waiting is recommended, you'll be seen regularly for reviews and invited to come back at any stage if you feel your symptoms are getting worse.

Chemotherapy

Chemotherapy is a widely used treatment for non-Hodgkin lymphoma, which involves using medicine to kill cancer cells. It may be used on its own, combined with biological therapy and/or combined with radiotherapy (see below).

The medication can be given in a number of different ways, depending on the stage of your cancer.

If doctors think your cancer is curable, you'll normally receive chemotherapy through a drip directly into a vein (intravenous chemotherapy). If a cure is unlikely, you may only need to take chemotherapy tablets to help relieve your symptoms.

If there's a risk of the cancer spreading to your brain, you may have chemotherapy injections directly into the cerebrospinal fluid around your spine.

Chemotherapy is usually given over a period of a few months on an outpatient basis, which means you shouldn't 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.

Chemotherapy can have several side effects, the most significant of which is potential damage to your bone marrow. This can interfere with the production of healthy blood cells and cause the following problems:

  • fatigue
  • breathlessness
  • increased vulnerability to infection
  • bleeding and bruising more easily

If you experience these problems, treatment may need to be delayed so you can produce more healthy blood cells. Growth factor medicines can also stimulate the production of blood cells.

Other possible side effects of chemotherapy include:

Most side effects should pass once your treatment has finished. Tell your care team if side effects become particularly troublesome, as there are treatments that can help.

Read more about the side effects of chemotherapy.

High-dose chemotherapy

If non-Hodgkin lymphoma doesn't get better with initial treatment (known as "refractory" lymphoma), you may have a course of chemotherapy at a stronger dose.

However, this intensive chemotherapy destroys your bone marrow, leading to the problems mentioned above. You'll need a stem cell or bone marrow transplants to replace the damaged bone marrow.

Radiotherapy

Radiotherapy is most often used to treat early-stage non-Hodgkin lymphoma, where the cancer is only in one part of the body.

Treatment is normally given in short daily sessions, Monday to Friday, over several weeks. You should not have to stay in hospital between appointments.

Radiotherapy itself is painless, but it can have some significant side effects. These can vary, depending on which part of your body is being treated. For example, treatment to your throat can lead to a sore throat, while treatment to the head can lead to hair loss.

Other common side effects include:

  • sore and red skin in the treatment area
  • tiredness
  • nausea and vomiting
  • dry mouth
  • loss of appetite

Most side effects are temporary, but there's a risk of long-term problems, including infertility and permanently darkened skin in the treatment area.

Read more about:

Monoclonal antibody therapy

For some types of non-Hodgkin lymphoma, you may have a type of medication called a monoclonal antibody.

These medications attach themselves to the surface of cancerous cells and stimulate the immune system to attack and kill the cells. They're often given in combination with chemotherapy to make the treatment more effective.

For some types of non-Hodgkin lymphoma, you may continue having monoclonal antibody treatment regularly for up to two years after initial treatment, in combination with chemotherapy. This can reduce the chances of the cancer coming back in the future.

One of the main monoclonal antibody medications used to treat non-Hodgkin lymphoma is called rituximab. This medication is administered directly into your vein over the course of a few hours.

Side effects of rituximab can include:

  • flu-like symptoms, such as a headaches, fever and chills
  • tiredness
  • nausea
  • an itchy rash

You may be given additional medication to prevent or lessen these side effects. Side effects should improve over time, as your body gets used to rituximab.

As rituximab has been so successful in treating non-Hodgkin lymphoma, 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 if you want to participate in one of these trials during your treatment.

Steroid medication

Steroid medication is commonly used in combination with chemotherapy to treat non-Hodgkin lymphoma. This is because research has shown that using steroids makes the chemotherapy more effective.

The steroid medication is normally given as tablets, usually at the same time as your chemotherapy. A short 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, which can lead to weight gain
  • indigestion
  • problems sleeping
  • feeling agitated

On rare occasions, you may have to take steroids on a long-term basis. Side effects of long-term steroid use include weight gain and swelling in your hands, feet and eyelids.

The side effects of steroid medication usually start to improve once treatment finishes.

Follow-up

After your course of treatment ends, you may have a repeat scan to see how well the treatment has worked. Following this, you'll need regular follow-up appointments to monitor your recovery and check for any signs of the cancer returning (known as a "relapse").

These appointments will start off being every few weeks or months, but become less frequent over time.

Want to know more?

For more information, see:

Complications

Some people treated for non-Hodgkin lymphoma experience long-term problems, even if they've been cured.

Some of the main complications of non-Hodgkin lymphoma are described below.

Weakened immune system

Having a weakened immune system is a common complication of non-Hodgkin lymphoma and it can become more severe while you're being treated.

However, your immune system will usually recover in the months and years after treatment.

If you have a weak immune system, you're more vulnerable to infections, and there's an increased risk of developing serious complications from infections. In some cases, you may be advised to take regular doses of antibiotics to prevent infections occurring.

It's also important to report any symptoms of an infection to your GP or care team 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:

  • a high temperature (fever)
  • headache
  • aching muscles
  • diarrhoea
  • tiredness
  • a painful blistering rash

Vaccination

You should make sure that all of your vaccinations are up to date.

However, it’s important to speak to your GP or care team about this because it may not be safe for you to have "live" vaccines (vaccines containing a weakened form of the virus or organism being vaccinated against) until several months after your treatment finishes.

Examples of "live" vaccines include the:

  • shingles vaccine
  • BCG vaccine (against tuberculosis)
  • MMR vaccine (against measles, mumps and rubella)

Infertility

Chemotherapy and radiotherapy for non-Hodgkin lymphoma can cause infertility. This is sometimes temporary, but it can be permanent.

Your care team will estimate the risk of infertility in your specific circumstances and let you know your options.

In some cases, it may be possible for men to store samples of their sperm and for women to store their eggs before treatment, so these can be used to try for a baby afterwards.

Second cancers

Having treatment for non-Hodgkin lymphoma can increase your risk of developing another type of cancer in the future. This is known as a "second cancer".

The risk of getting cancer is particularly increased after cancer treatment because chemotherapy and radiotherapy damage healthy cells, as well as cancer cells. This damage can then cause the affected cells to become cancerous many years after treatment.

You can help to reduce your risk of a second cancer by adopting a healthy lifestyle through not smoking, maintaining a healthy weight with a balanced diet, and getting regular exercise.

You should report any symptoms that might suggest another cancer to your GP at an early stage and attend any cancer screening appointments you're invited to.

Other health problems

Treatment for non-Hodgkin lymphoma can increase your risk of getting certain conditions at a younger age than normal, such as:

Having a cancer diagnosis can also increase your risk of depression.

You should report unexpected symptoms, such as increasing shortness of breath, to your GP.