What is classical Hodgkin lymphoma?
Classical Hodgkin lymphomas are cancers of the lymphatic system.
Doctors identify Hodgkin lymphoma by a particular type of cell it contains – Reed-Sternberg cell – which isn’t present in non-Hodgkin lymphoma. If you are not sure what type of lymphoma you have, ask your doctor. Each type of lymphoma can behave and be treated differently.
What are the different types of classical Hodgkin lymphoma?
There are 4 types of classical Hodgkin lymphoma:
- nodular sclerosing – about 70 out of every 100 cases
- mixed cellularity – about 25 out of every 100 cases
- lymphocyte-rich – about 5 out of every 100 cases
- lymphocyte-depleted – fewer than 1 in every 100 cases.
The types of classical Hodgkin lymphoma are named after the different appearances of the lymphoma cells and the cells in the tissue surrounding them. All types of classical Hodgkin lymphoma are treated in the same way.
Nearly 2,000 cases of classical Hodgkin lymphoma are diagnosed in the UK each year. You can get Hodgkin lymphoma at any age, but most people diagnosed are between the ages of 15 and 34 or then 60 and over. Overall, more males than females get Hodgkin lymphoma.
Scientists don’t know exactly what causes classical Hodgkin lymphoma, but known risk factors include:
Other risk factors, including some autoimmune diseases and relevant family history, have also been linked with Hodgkin lymphoma.
About 45 out of 100 cases of Hodgkin lymphoma are related to a past infection with the Epstein-Barr virus (EBV). This is a common virus that causes glandular fever (infectious mononucleosis). People who have been infected with EBV have between 3 and 6 times higher risk of developing Hodgkin lymphoma compared with the general population. Because EBV is a very common virus, having it doesn’t mean that you will get classical Hodgkin lymphoma – it just means your risk is slightly increased. Scientists don’t know why some people who have had EBV get lymphoma while most don’t.
Two risk factors for Hodgkin lymphoma are related to having lower than normal immunity. These are:
People who have HIV are 10-20 times more likely to develop lymphoma compared with the general population. This is partly because they are more likely to get infected with EBV, but partly because of the HIV infection itself.
People who’ve had an organ transplant have to take medication to suppress their immune system. Lowered immunity increases the risk of getting an EBV infection, which increases the risk of getting Hodgkin lymphoma.
Other risk factors have been linked to developing Hodgkin lymphoma, but the evidence to support each of these is less strong than it is for EBV infection or lowered immunity. Other risk factors include:
- having an autoimmune disease (such as rheumatoid arthritis or systemic lupus erythematosus). The increase in risk varies depending on the type of autoimmune disease.
- having a close family member diagnosed with Hodgkin lymphoma. Having a relative with Hodgkin lymphoma makes you 3 times more likely to develop the condition. Although this sounds worrying, it is still a small risk because Hodgkin lymphoma is rare.
The most common symptom of classical Hodgkin lymphoma is one (or more) swollen lymph node. It is usually painless. It is often in the neck, but can be elsewhere in the body, eg in the armpit, the groin or the centre of the chest (the mediastinum).
- fevers (temperature above 38ºC)
- drenching sweats, especially at night
- unexplained weight loss (more than 10% in 6 months).
Fevers associated with classical Hodgkin lymphoma come and go, lasting from a few days to 2 weeks at a time. Some people have other general symptoms, such as itching and tiredness.
A relatively uncommon symptom is pain after drinking alcohol, which happens in fewer than 1 in 10 people diagnosed. Areas of the body that contain lymphoma become painful within a few minutes of drinking even a small amount of alcohol. Although this symptom isn’t common, it is a strong sign of Hodgkin lymphoma.
Rarely, Hodgkin lymphoma starts in a body organ rather than a lymph node.
The main way to diagnose any type of lymphoma is to remove a swollen lymph node, or a sample of cells from it, and look at it under a microscope. This is done in a small operation called a biopsy, which is usually done under a local anaesthetic.
The sample is then sent to a specialised laboratory where doctors experienced in diagnosing lymphoma examine it. The lymph node cells are tested for particular proteins that are found on the surface of lymphoma cells.
It may take a while to have all the necessary tests done on your biopsy. The results help your doctor diagnose which type of lymphoma you have and then decide on the treatment it is most likely to respond to.
Once you have been diagnosed, you need other tests to find out which areas of your body the lymphoma is growing in - this is called 'staging'. You have blood tests and scans. Doctors do blood tests to:
- check your blood cell counts to look at your general health and make sure you’re not anaemic
- make sure your kidneys and liver are working well
- rule out infections that could flare up when you have treatment, such as hepatitis
- look for inflammation in your body, eg using a blood test called the erythrocyte sedimentation rate (ESR).
Most people have a PET scan and a CT scan. Some people, particularly children, may have an MRI scan instead of, or as well as, a PET/CT scans.
Rarely, you may also have a sample of your bone marrow cells taken (a bone marrow biopsy), to check if you have lymphoma cells in your bone marrow.
You usually have each of these tests done as an outpatient. It takes a few weeks to get all the results. Waiting for test results can be a worrying time, but it is important for your doctor to gather all of this information in order to plan the best treatment for you.
Classical Hodgkin lymphoma generally responds very well to treatment. The majority of people are cured, even if their lymphoma is advanced when it is diagnosed.
The outcome depends on the stage of your lymphoma when it is diagnosed and on other aspects of your lymphoma that doctors use to predict outcome. They have identified these aspects through many decades of research. Your doctor may refer to ‘risk factors’ or your 'International Prognostic Score (IPS)'. The IPS is sometimes called the Hasenclever score. These features may be taken into account when your doctor plans your treatment.
Your lymphoma specialist is the best person to talk to about the likely outcome of your treatment. They can’t give guarantees, but having access to all your test results and treatment plan means they are able to give you a more informed prognosis (outlook).
The exact treatment for classical Hodgkin lymphoma depends mainly on the stage of your disease. Stage 1 or 2 Hodgkin lymphoma is known as ‘early’ disease. Stage 3 or 4 is known as ‘advanced’ disease. Just over half of cases (55%) of all types of Hodgkin lymphoma are early stage at diagnosis.
In addition, your doctor takes into account:
- your age, general health and fitness
- your feelings about treatment and what may be important to you in the future, such as having children.
Sometimes your doctor takes into account your IPS or risk factors.
When choosing your treatment, your doctor also considers any potential long-term effects it may have. This is important because treatment for Hodgkin lymphoma is often successful and people can live for many years after their lymphoma has gone into remission (no evidence of disease).
Doctors continue to research less intensive treatments for Hodgkin lymphoma. They aim to find treatments that have as few side effects and late effects as possible. Late effects are rare, but they can cause health problems a long time after the lymphoma has been cured. Your medical team should explain the possible side effects and late effects of your planned treatment.
You may have PET scans during your treatment. Your doctors use them to tell how your lymphoma is responding to avoid giving you more treatment than you need. They may also decide to change your treatment if the response is less than expected. This approach can help to minimise the likelihood of problems in the future, after your lymphoma has been cured.
Treatment for early stage classical Hodgkin lymphoma
- A – doxorubicin (Adriamycin®)
- B – bleomycin
- V – vinblastine
- D – dacarbazine.
You have all these drugs every 2 weeks intravenously (as an injection into a vein or through a drip). The 2-week break allows your body to recover between treatments. Each 4 weeks of treatment is called a ‘cycle’. Most people have between 2 and 4 cycles of treatment. If you have unfavourable prognostic factors, you are more likely to get more cycles of treatment.
A few weeks after your chemotherapy finishes, you are likely to have radiotherapy to the areas affected by your lymphoma. You are most likely to have between 2 and 4 weeks of daily treatments (Monday to Friday).
Sometimes people with classical Hodgkin lymphoma have chemotherapy alone. Chemotherapy without radiotherapy is less likely to cause long-term side effects, but the risk of the Hodgkin lymphoma relapsing (coming back) is slightly increased. Your doctor should discuss the treatment choices with you and should take your views and wishes into account.
Treatment for advanced stage classical Hodgkin lymphoma
Advanced stage classical Hodgkin lymphoma is also usually treated with chemotherapy, but you are likely to have more cycles of treatment. Most people with advanced stage classical Hodgkin lymphoma do not get radiotherapy. ABVD is the most common combination of chemotherapy drugs used, but there are other options. For example, doctors can use BEACOPP, which contains bleomycin, etoposide, doxorubicin (Adriamycin®), cyclophosphamide, vincristine, procarbazine and a steroid prednisolone.
BEACOPP works well although it is more likely to have long-term side effects than ABVD.
Treatment for people over 60
About a quarter of all people diagnosed with Hodgkin lymphoma are 60 or over, but age alone may not affect treatment. If you have other health problems, such as heart disease, you may have less intensive treatment or a different combination of chemotherapy drugs than you would otherwise have.
Your doctors want to give you as much treatment as is safe and effective. They need to balance this against the risks of making you more ill with the treatment and its likely complications.
ABVD may be given to people over 60. However, other chemotherapy regimens are used more often in this age group:
- ChlVPP (chlorambucil, vinblastine, procarbazine and prednisolone)
- VEPEMB (vinblastine, cyclophosphamide, procarbazine, etoposide, mitoxantrone and bleomycin, and the steroid prednisolone).
These regimens do not include drugs that can cause heart problems.
Treatment for people under 18
You have regular follow-up appointments with your specialist after you finish your treatment. At first, these are scheduled roughly every 3 months. If all is well, they gradually become less frequent.
At your appointments, your doctor examines you and asks if anything is troubling you. You may have occasional tests or scans, but generally these are not necessary if you don’t have any symptoms. As time goes on, you may have other tests to check for late effects, such as heart scans or thyroid hormone tests.
Many people are discharged from follow-up after several years if their Hodgkin lymphoma has not come back. The timescale varies depending on your individual circumstances, but most people are discharged 2-5 years after treatment has finished.
Relapsed and refractory classical Hodgkin lymphoma
In a small number of people, classical Hodgkin lymphoma is refractory (does not respond to treatment) or relapses (comes back). In either event, there are other treatments that your doctor can suggest.
Some people can be given radiotherapy to the areas affected by lymphoma.
If your Hodgkin lymphoma has not responded to treatment, or has come back, you may have chemotherapy with a different combination of drugs from the ones you had first time round. If you are fit enough, doctors may give you more intensive chemotherapy and collect your stem cells. They may then use a combination called BEAM together with a stem cell transplant. BEAM stands for the following drugs:
- B – BiCNU® or carmustine
- E – etoposide
- A – Ara-C or cytarabine
- M – melphalan
You have these chemotherapy drugs for a week and then you have a stem cell transplant. This is because the drugs in this combination kill your blood stem cells, as well as the lymphoma cells. You need to have a transfusion of your own stem cells or stem cells from a donor to replace the ones you have lost.
A stem cell transplant is an intensive treatment. You need tests beforehand to make sure you are fit enough to have it. If you are not, there are targeted treatments and experimental treatments that your doctor may suggest.
Research and targeted treatments
Although treatment for classical Hodgkin lymphoma is often successful, doctors continue to do research. The main aims of research are to reduce long- and short-term side effects and to find better treatments for those whose classical Hodgkin lymphoma doesn’t respond to treatment or comes back.
Several clinical trials have looked at a targeted therapy called brentuximab vedotin. This is a monoclonal antibody that targets Hodgkin lymphoma cells and carries a chemotherapy drug. It is sometimes called an ‘antibody-drug conjugate’. The idea is that the antibody finds the lymphoma cells and delivers the chemotherapy directly to them.
Trials have already shown that brentuximab vedotin may be helpful for people whose Hodgkin lymphoma has:
- come back or not responded after at least 2 types of treatment
- come back after a stem cell transplant.
Brentuximab vedotin is in clinical trials to see if it can help other people with classical Hodgkin lymphoma.
Other clinical trials are looking at ways to reduce the number of people who need radiotherapy after chemotherapy. People with a good response to chemotherapy may not need radiotherapy, lowering their risk of late effects.
It is too early to say whether any of these new treatments or approaches to treatment work better than those doctors already use. Your medical team may offer you the chance to take part in a clinical trial, if there is one suitable for you.
You can find out more about clinical trials and search for a trial that might be suitable for you at Lymphoma TrialsLink.