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What is non-Hodgkin lymphoma or NHL?
‘Non-Hodgkin lymphoma’ or NHL is a type of cancer that starts in white blood cells, called ‘lymphocytes’, which help protect the body from infection. Lymphocytes travel continuously around the body through a network known as the ‘lymphatic system’, which includes the spleen, thymus, appendix, tonsils and bean-shaped glands called ‘lymph nodes’.[1]

In non-Hodgkin lymphoma, lymphocytes become abnormal and lose the ability to control their growth and how quickly copies of the lymphocyte are made (‘proliferation’). The abnormal lymphocytes tend to collect in lymph nodes, causing them to swell and form cancerous tumours. There are hundreds of lymph nodes in the body – some are close to the surface and can be felt with the fingers, such as those in the armpits, neck and groin, but other lymph nodes are deep inside the body, such as those around the heart and lungs.

Non-Hodgkin lymphoma or NHL can start almost anywhere in the body. Abnormal lymphocytes might collect in more than one lymph node, and they can travel to other parts of the lymphatic system, such as the spleen. They can also enter the bloodstream, causing the cancer to spread to other organs. When NHL develops outside of the lymphatic system, it is called ‘extranodal disease’. Extranodal sites include the lungs, liver, blood, bone marrow, kidneys, brain and spinal cord.

Types of NHLs
There are many different types of non-Hodgkin lymphoma or NHL, and they can be classified in several different ways.

There are two types of lymphocytes, ‘B-lymphocytes’ or ‘B-cells’ and ‘T-lymphocytes’ or ‘T-cells’. One way to classify NHL is by the type of lymphocyte that the lymphoma starts in. Most people (about 9 out of 10) with NHL have B-cell lymphoma.[2]

Another way to classify NHL is by how fast the lymphoma grows. ‘Low-grade’ (also called ‘indolent’) types of NHL tend to grow slowly and cause few symptoms until late in the disease. In some situations, people with low-grade NHL may not need treatment for many years. ‘High-grade’ (also called ‘aggressive’) types of NHL grow quickly, cause symptoms, and need treatment straightaway.

‘Follicular lymphoma’ or FL is the most common type of low-grade NHL, and the second most common type of lymphoma.[3][4] It usually begins in the lymph nodes, but because it is slow-growing and causes few symptoms, it has often spread around the body at the time of diagnosis.[5] People with FL usually respond well to treatment, initially and also when the disease eventually re-appears again. It is also observed that between 2 and 3 out of every 100 FLs change into high-grade NHLs every year.[6] In addition to FL, other types of low-grade NHL exist, for example ‘marginal zone lymphoma’ and ‘small lymphocytic lymphoma’[7].

‘Diffuse large B-cell lymphoma’ or DLBCL is the most common type of non-Hodgkin lymphoma, and by far the most common type of aggressive NHL. The term ‘diffuse’ means that the abnormal lymphocytes do not collect in one particular part of the lymph node.[8] DLBCL mainly affects elderly patients, but it can also happen in children and adults. With quick and appropriate treatment, DLBCL can be cured in between 5 and 8 of every 10 patients.[8] Other types of high-grade or aggressive NHLs include for example ‘Burkitt lymphoma’, ‘peripheral T-cell lymphoma’ and ‘mantle cell lymphoma’.

What are the risk factors for NHL?
The cause of non-Hodgkin lymphoma is not known. It seems to start in one single abnormal lymphocyte, which then multiplies and produces many abnormal lymphocytes. The reason the first lymphocyte becomes abnormal is not known.

NHL is not a disease that can be inherited, and does not run in families. There are some things that can increase a person’s chances of getting NHL, called ‘risk factors’.[9] Some risk factors are:

  • Age – NHL tends to affect people older than 60 years of age.
  • Sex – NHL is slightly more common in men than women.
  • Immune deficiencies – people with weakened immune systems (for example, people with AIDS) have a higher risk of developing NHL.
  • Autoimmune disease – people with diseases that cause the immune system to attack a certain part of the body have an increased risk of developing NHL.
  • Infection – some viruses and bacteria can cause NHL.

What are the stages of NHL?
The stage of NHL refers to how much the disease has spread at the time it is diagnosed. This can help decide a patient’s treatment and the likelihood of reaching a disease-free period (‘remission’). The staging system that is commonly used for non-Hodgkin lymphoma or NHL is:

  • Stage 1 – the lymphoma is only in one lymph node region or lymphatic area.
  • Stage 2 – the lymphoma is affecting two or more lymph node regions on the same side of the diaphragm (large muscle that separates the chest from the tummy).
  • Stage 3 – the lymphoma is affecting two or more lymph node regions or one lymph node and one organ on opposite sides of the diaphragm.
  • Stage 4 – the lymphoma is affecting parts of the body outside of the lymphatic system.

Stages 1 and 2 are sometimes called ‘early-stage NHL’, and stages 3 and 4 are often called ‘advanced NHL’.

B-symptoms
The letter A or B is given after each stage number. This shows whether or not a person has the following symptoms:

  • Drenching night sweats.
  • Unexplained weight loss.
  • Unexplained fever.

The letter A means a person does not have these symptoms, while the letter B means they do, which is why they are called B-symptoms.

Extranodal lymphoma
When NHL develops outside of the lymphatic system, it is called ‘extranodal disease’. Extranodal disease has the letter E after the stage number.

What are the treatment options for NHL?
Treatment of NHL depends on the type and stage of the disease. Other things that are thought about when deciding on treatment are:

  • Age.
  • Overall health.
  • Overall physical condition.
  • Whether there are certain changes in the genes.
  • The amount of ‘lactate dehydrogenase’ (LDH) in the blood.
  • Whether the lymphoma has just been diagnosed or has come back after treatment.

Treatments for NHL include:

  • Chemotherapy.
  • Biological therapy.
  • Radiotherapy.
  • Stem cell transplant.
  • Watch and wait.

Chemotherapy is a type of treatment that uses drugs to destroy cancer cells or to stop them from multiplying.[10] High-grade or aggressive NHLs are usually treated with a mixture of chemotherapy drugs.[11] Chemotherapy is also used to treat low-grade or indolent NHLs when the doctor has decided active treatment is needed.[11] Chemotherapy is more likely to be able to cure high-grade NHLs than low-grade NHLs, but it may stop symptoms from happening in low-grade NHLs for months or years.

‘Biological therapies’ (small proteins) are sometimes used with chemotherapy. This type of therapy uses the body’s own immune system to treat the lymphoma. There are several different types of biological therapies. ‘Monoclonal antibodies’ are a type of biological therapy that are able, for example, to find and attach to certain B-cells, helping other cells in the immune system remove them.

Radiotherapy uses high-energy beams of radiation that are focused on the area of the body where the lymphoma is located. Radiotherapy kills cancer cells, or stops them from multiplying. It is usually only used if the lymphoma is in one or two lymph nodes.[12]

‘Stem cell transplant’ or ‘bone marrow transplant’ is sometimes given after high doses of chemotherapy.[13] This is needed because high-dose chemotherapy not only destroys abnormal cells but also destroys healthy cells that protect people from infection. These stem cells grow into healthy new blood cells.

‘Watch and wait’ is often the first approach for low-grade or indolent NHLs that are causing no symptoms [14] Patients are closely followed during this time, and treatment is not given until the disease causes symptoms. 

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