Non-Hodgkin lymphoma

Lymphoma is a tumour of the lymphocytes, the white blood cells that defend the body against infection. Lymphocytes do not live in the blood alone: their real place of work is the lymph nodes, the spleen, the bone marrow and the lymphatic vessels that run through the whole body. When one clone of these cells starts dividing without restraint, it piles up exactly where it belongs — and a node grows. The name non-Hodgkin lymphoma covers not one disease but more than thirty: some drag on for decades, others double in a matter of weeks. What they share is that most respond well to treatment and many are cured outright.

A node that will not settle

The commonest first sign is an enlarged lymph node in the neck, above the collarbone, in the armpit or in the groin. It usually does not hurt, feels firm and rubbery, the skin over it stays its normal colour, and unlike the node that comes up with tonsillitis it does not shrink back in a week or two but slowly grows.

The main thing is worth saying straight away: nodes swell because of infection hundreds of times more often than because of lymphoma, and an enlarged node on its own almost never means a tumour. It needs showing to a doctor if it lasts more than three or four weeks, keeps growing, is painless and hard, or has come up above the collarbone.

Some nodes cannot be felt at all — those inside the chest and the abdomen. They make themselves known differently: a dry cough, breathlessness, a sense of pressure behind the breastbone, a full or bloated abdomen, feeling full after a few mouthfuls, a dull ache in the side. Occasionally lymphoma starts not in a node but in an organ — the stomach, the bowel, a tonsil or the skin — and then the first complaint is whatever that organ produces.

Signs rarely put down to lymphoma

Some people have general symptoms long before they see anyone about them. Taken singly each looks harmless; together they add up to a picture doctors know well.

• night sweats heavy enough to mean changing the bedding, not simply a warm night;
• weight loss with no diet and no explanation;
• temperatures with no sign of infection, sometimes for days on end, sometimes in waves;
• itching all over the body with no rash at all, occasionally months before anything else;
• a wearing tiredness and breathlessness on exertion that used to be easy.

If the tumour cells have reached the bone marrow, the making of normal blood cells suffers: pallor and weakness from anaemia set in, infections follow one after another, bruises appear from the lightest knock along with pinprick bleeding into the skin, and the gums and nose start to bleed.

When waiting is not an option

Most reasons to see a doctor about lymphoma can wait for an appointment. A few situations are counted in hours.

• A temperature of 38 °C or higher during chemotherapy or in the weeks after it. Treatment drives the white cell count down, and an ordinary infection turns into sepsis within hours. This is not something to sleep on or to treat at home with paracetamol: contact your team at once or go straight to hospital.
• Swelling of the face and neck, distended veins on the chest, breathlessness that is worse lying flat. This is how a tumour in the chest pressing on the main vein back to the heart shows itself, and it needs an ambulance.
• Increasing weakness in the legs, numbness around the perineum, retention or loss of bladder control, a band of pain around the back. These point to pressure on the spinal cord; the sooner treatment starts, the better the chance of keeping movement.
• Sudden breathlessness, chest pain, heavy bleeding or confusion.

The single European emergency number is 112, in use in Spain, Italy, Portugal, Poland and Ukraine.

What raises the risk

Why the DNA inside a lymphocyte goes wrong is unknown in most cases. What is known is that nearly every established risk factor has something to do with the immune system.

• illnesses and treatments that weaken it: HIV infection, the medicines taken after an organ transplant, long-term immunosuppression;
• autoimmune conditions such as rheumatoid arthritis, lupus, Sjögren's syndrome and coeliac disease;
• certain infections: Epstein-Barr virus, hepatitis C virus, HTLV-1 and, for lymphoma of the stomach, the bacterium Helicobacter pylori;
• chemotherapy or radiotherapy given in the past for another cancer;
• age, since the risk climbs over the years, and sex, as it is slightly commoner in men;
• lymphoma in a close relative, which raises the risk only a little.

Lymphoma is not catching and is not inherited. Stress, injury and diet do not cause it.

How the diagnosis is made

There is only one way to confirm lymphoma: examining tissue from a node. The doctor examines and feels every group of nodes along with the liver and spleen and orders blood tests, but the final answer comes solely from the pathologist who has looked at the tissue down a microscope.

One detail costs people months. Fine-needle aspiration is no use for diagnosing lymphoma. A fine needle draws out loose cells, whereas the pathologist has to see how the whole node is built: whether its architecture survives, what has replaced it, how the cells are arranged. That is why either the whole node is taken out or a core of tissue is taken with a thicker needle under ultrasound guidance. If an aspiration comes back saying no tumour cells were found and the node carries on growing, that does not remove the need for a proper biopsy.

Once the type of lymphoma is settled, further tests map out how far it has spread and prepare for treatment: blood tests including LDH, a CT or PET-CT scan, a bone marrow biopsy where needed and, if the nervous system may be involved, a lumbar puncture. Before treatment begins, heart function is checked, along with blood tests for hepatitis B and C and for HIV.

What stage and grade mean

These are two different things and worth keeping apart: the stage says how far the disease has travelled, the grade how fast it grows.

There are four stages. In the first one group of nodes is involved; in the second several, but all on one side of the diaphragm; in the third both sides are affected; in the fourth the lymphoma has moved outside the lymphatic system into the bone marrow or internal organs. A letter is added to the number: A for no general symptoms, B where there is fever, night sweats or weight loss, and E for a site outside the nodes.

There are two grades. Indolent lymphoma grows slowly and may cause no trouble for years; aggressive lymphoma moves fast and has to be treated at once. Hence a paradox that catches people out: aggressive lymphomas respond better to treatment and are often cured completely, while indolent ones can be held in check for years but are harder to get rid of altogether. An indolent lymphoma sometimes transforms into an aggressive one over time, betrayed by a node that grows quickly, fever coming back and weight falling away.

How it is treated

The plan depends on the type of lymphoma, the stage, your age and other illnesses, and it is worked out by a team rather than one doctor. There is usually enough time to ask questions and talk it over with the people close to you.

• Watch and wait. With an indolent lymphoma causing no symptoms, treatment is often postponed and you are simply seen regularly. This is not care being withheld: starting chemotherapy early in that situation does not lengthen life, while the side effects arrive all the same.
• Treating the infection. In lymphoma of the stomach linked to Helicobacter pylori, a course of antibiotics often makes the tumour disappear — a rare instance of a cancer treated with tablets meant for gastritis.
• Chemotherapy, usually several medicines given in cycles, into a vein or as tablets, mostly as a day case. If the nervous system is at risk, the medicine is put into the fluid around the spinal cord.
• Monoclonal antibodies. Rituximab and its relatives label the tumour cells so that the immune system destroys them. Hepatitis B is always checked first: in anyone who has had it the virus can wake up, and antiviral cover is then prescribed.
• Radiotherapy, for early stages and for individual bulky sites.
• Targeted medicines, steroids and cell therapy. If the disease returns or fails to respond to first treatment, high-dose chemotherapy with a stem cell transplant is used, or CAR-T therapy, made from your own modified immune cells.

What to sort out before the first cycle

Two things lose their point if left until later. The first is storing sperm or eggs: chemotherapy and radiotherapy can take fertility away permanently, so this is decided before treatment starts rather than after it ends. The second is the dentist, if radiotherapy to the head and neck lies ahead: irradiated jaw bone heals badly and having a tooth out afterwards becomes a problem in its own right, so any bad teeth are dealt with in advance.

Life after treatment

A scan is done once the course finishes, and after that check-ups are repeated, closely together at first and then further and further apart. It is not only the return of the disease that is being watched for.

• The immune system takes months, sometimes years, to recover. Any infection during that time is treated promptly and not at home: a temperature, shivering or a painful blistering rash is a reason to contact your doctor the same day. Vaccinations are needed, but live vaccines are off limits during treatment and for some months afterwards, and the timing is checked with your team.
• Heart and lungs. Some chemotherapy drugs and irradiation of the chest tell on them in time, so breathlessness that is getting worse on ordinary exertion should be shown to a doctor rather than blamed on age.
• Thyroid. After the neck has been irradiated it often becomes underactive. Feeling the cold, sluggishness, weight gain and dry skin are a reason to have the hormones tested rather than to put up with it.
• Second cancers. The risk of another cancer after treatment is higher than usual, which makes not smoking and turning up for screening programmes matter more than ever.
• Mood. Anxiety and low spirits after a long course of treatment are entirely usual, and asking for help with them is as legitimate as with any other after-effect.

Online consultation with a doctor

A remote appointment suits everything that happens between hospital visits. Going through blood results and the scan report, working out what indolent lymphoma means in your case and why watching has been suggested instead of treatment. Talking about side effects, sickness, weakness, skin changes, food, vaccinations, travel and work. Putting together the list of questions for the haematologist so that they do not come back to you out in the corridor.

The limits are obvious. Nodes have to be felt by hand, a biopsy cannot be done through a screen, and with a temperature during chemotherapy, swelling of the face and neck or growing weakness in the legs what is needed is not a conversation but an ambulance.

This material is for information only and does not replace medical advice.