Lymphoma and HIV

Lymphoma is a type of cancer. Cancer develops when cells undergo changes that allow them to grow and survive in ways that are no longer properly controlled by the body. These ‘malignant’ cells may invade nearby tissues, spread to other parts of the body, or avoid normal immune checks.

Cancers are often named after the tissue or cell type they arise from. For example, lymphoma starts in lymphocytes, a type of white blood cell involved in the immune system. Lymphocytes are found in the blood, lymph nodes, spleen, bone marrow and other tissues. Many of them move through the lymphatic system, a network of vessels, nodes and organs that helps the immune system monitor the body for infections and other threats.

Lymph nodes are small, bean-shaped organs where immune cells gather, communicate and respond to infections. During infections they can become swollen because immune cells are multiplying and becoming activated.

Lymph nodes are found throughout the body, including in the neck, armpits and groin, as well as deeper inside the chest, abdomen and pelvis; they are usually small and difficult to feel. Swollen lymph nodes are often caused by infections, but a lump that is hard, fixed in place, painless or does not go away should be checked by a doctor as it may be a sign of cancer.

While there are several types of cancer that affect the immune system itself, lymphomas affect a branch of it called the adaptive immune system. This is composed mainly of T and B lymphocytes – including CD4 cells, which are a subtype of T lymphocytes.

This adaptive branch is responsible for creating immune memory, responding to vaccines and fighting infections in a more targeted way. During untreated HIV infection, the adaptive immune system is not simply weakened; it is also repeatedly stimulated, like an alarm that cannot switch off. Over time this can lead to exhaustion, loss of CD4 cells and abnormal patterns of cell division.

There are over 60 different types of lymphoma, broadly grouped into Hodgkin lymphoma and non-Hodgkin lymphoma. The type of lymphoma you have may determine which type of treatment is best for you.

The type of lymphoma is determined by which lymphocytes become cancerous. Hodgkin lymphoma usually arises from B lymphocytes, while non-Hodgkin lymphoma can involve any lymphocyte or natural killer cells. The distinction also involves other characteristics seen when the lymphocytes are examined under a microscope. For example, cells called Reed-Sternberg cells are the main defining feature of classical Hodgkin lymphomas, while in non-Hodgkin they are usually absent.

Hodgkin lymphoma

Hodgkin lymphoma (HL) is broadly divided into two categories. Nine in ten people have ‘classical’ Hodgkin lymphoma. Nodular lymphocyte-predominant B cell lymphoma is rarer and behaves differently.

Classical Hodgkin lymphoma is further divided into four subtypes according to how the lymph node tissue looks under the microscope, including the pattern of scarring and the types of immune cells surrounding the Reed-Sternberg cells. These subtypes are nodular sclerosing, mixed cellularity, lymphocyte-rich and lymphocyte-depleted Hodgkin lymphoma.

Among these subtypes, nodular sclerosing and mixed cellularity are the most frequent. Nodular sclerosing is defined by the presence of large amounts of scar tissue in the lymph nodes, while mixed cellularity features Reed-Sternberg cells surrounded by a mixture of other inflammatory immune cells. Mixed cellularity is typical for older people in the general population and is also the most common type of classical Hodgkin lymphoma in people with HIV. This subtype is also strongly associated with the presence of Epstein Barr virus – a very common type of herpesvirus that becomes more active and harmful once the immune system is weakened.

Non-Hodgkin lymphoma

Based on cell type of origin, two of the most common subtypes of non-Hodgkin lymphoma (NHL) in people with HIV are diffuse large B-cell lymphoma and Burkitt lymphoma.

NHL is also classified according to the speed of its growth, as ‘indolent’ or ‘aggressive’. Indolent lymphomas grow slowly and often respond well to treatment, but at later stages they can be difficult to cure completely and may become a long-term condition. Aggressive lymphomas grow more quickly, but some types respond very well to prompt treatment and can sometimes be cured.

Lymphoma in people living with HIV

Non-Hodgkin lymphoma (NHL) is one of the two most common cancers in people living with HIV in the UK (the other is Kaposi's sarcoma). There are fewer cases of Hodgkin lymphoma, but it is still one of the ten most common cancers in people with HIV.

The damage HIV does to the immune system makes people living with HIV more vulnerable to lymphoma than other people. The risk is greatest in people who are not taking effective HIV treatment, but even with treatment, people living with HIV are about ten to twenty times more likely to develop NHL than people without HIV. People living with HIV are about five to fifteen times more likely to develop HL than people without HIV.

A low CD4 count increases the risk, especially of NHL. Similarly older age increases the risk as the immune system weakens with age.

People with HIV are more likely than other people to be diagnosed when their lymphoma is at a more advanced stage. In people with HIV, lymphoma (especially NHL) may also spread faster, involving organs outside the lymph nodes, such as the bone marrow, liver, or lungs.

In a person living with HIV, some aggressive forms of NHL may be described as an ‘AIDS-defining’ cancer. This is because it usually occurs when the immune system is very weak.

Hodgkin lymphoma is usually a highly treatable cancer, and many people can be cured, especially when it is diagnosed and treated promptly. The responses of people with well-controlled HIV to cancer treatment are similar to those without HIV.

Non-Hodgkin lymphoma is sometimes more difficult to treat but that varies according to immune status, age and subtype of the cancer.  It’s important to know that treatment for NHL can work very well in people living with HIV. The responses of people with well-controlled HIV to cancer treatment are similar to those without HIV.

If you are diagnosed with lymphoma but you haven’t been tested for HIV, your doctor might suggest you take an HIV test. This is because people who have lymphoma sometimes have HIV without realising it.

What are the symptoms of lymphoma?

The symptoms, tests and treatments described below can apply to both Hodgkin lymphoma and non-Hodgkin lymphoma, but the exact approach depends on the lymphoma subtype, stage, location, HIV control, CD4 count and general health.

You may not notice anything, but lymphoma can cause a painless lump or swelling, often in the neck, armpit or groin (a swollen lymph node).

Lymphoma in the stomach or bowel may cause indigestion, abdominal pain or weight loss.

Lymphoma in the chest area may result in a cough, difficulty swallowing or breathlessness.

You might also have weight loss, fever, or night sweats – the so-called “B symptoms”.

How is lymphoma diagnosed?

The most important test for diagnosing lymphoma is a biopsy. This usually means taking a sample from an enlarged lymph node or another affected tissue. In some cases, a bone marrow biopsy may also be needed to check whether lymphoma involves the bone marrow.

Some people will be given a general anaesthetic and so will be asleep when it is done, while other people will only need a local anaesthetic, which numbs the area. The tissue sample is then sent to a laboratory to be checked for lymphoma cells.

You may also need a CT (computerised tomography) scan. This takes X-ray images from multiple angles, which build up a three-dimensional picture of the inside of your body. This allows your doctors to see how far the lymphoma has spread and if treatment is working.

A CT scan involves you lying on an examination table which slides through a large machine. You will usually need to drink or be injected with a type of dye (called a contrast agent) before the procedure.

Depending on the type of lymphoma you have, you might have a PET/CT scan, which combines a CT scan with a PET scan. The PET scan uses low-dose radiation to measure the activity of cells in different parts of the body – it gives more detailed information about which parts of the body have active (growing) lymphoma.

Blood tests will also be needed to measure the amounts of certain types of cells and biological markers in your blood. 

With the information from these tests, your lymphoma will be ‘staged’. This describes where lymphoma is found in the body and how widely it has spread. The stages range from 1 to 4:

• Stage 1 is assigned to a lymphoma localised in one lymph node region or in one organ outside the lymphatic system.
• Stage 2 describes a lymphoma that has spread to two or more lymph node regions but all on the same side of the diaphragm (the breathing muscle).
• Stage 3 is when the lymphoma has spread to lymph nodes both above and below the diaphragm.
• Stage 4 means lymphoma is more widespread and involves organs outside the lymphatic system, such as the bone marrow, liver or lungs, rather than only nearby lymph nodes or one limited area. Unlike many other cancers, stage 4 lymphoma is often still highly treatable although this may depend on the lymphoma subtype.

Letters are also assigned to each stage that help further clarify the clinical picture. You might be told you are at stage 3B or 4A, for example.

• Letter A means the person does not have “B symptoms”.
• Letter B means the person has at least one of these symptoms: unexplained fever, drenching night sweats or unintentional weight loss. B symptoms are especially important in the staging of Hodgkin lymphoma.
• Letter E is used when lymphoma involves a single area outside the lymphatic system or has spread directly from nearby lymph nodes into a neighbouring tissue or organ.

How is lymphoma treated?

When considering your treatment options, you and your healthcare team should consider the type of lymphoma you have, how advanced it is, which part(s) of your body are affected, your general health, and your personal priorities.

Depending on your circumstances, treatments may have different aims. These may be to try to cure the lymphoma, to control it for as long as possible, or to relieve symptoms.

You should ask your doctor about the possible benefits of a treatment, what risks and side-effects could be involved, what other treatments are available, and what is likely to happen without treatment.

Chemotherapy is the main treatment for most types of lymphomas. It uses strong drugs to destroy cancer cells and prevent the cancer from spreading. Chemotherapy drugs kill cells that are growing fast, including cancer cells. However, they can’t tell the difference between cancer cells and normal fast-growing cells in the body – this is what causes the side-effects of chemotherapy.

A combination of different chemotherapy drugs may be given into a vein (intravenously), as tablets, or by another method. Depending on the chemotherapy regimen, you may be able to visit the hospital as an outpatient (day patient), or you might need to stay in hospital for a few days.

Monoclonal antibodies are man-made antibodies designed to recognise specific markers on cancer cells. For example, rituximab targets a marker called CD20 and is commonly used for many B-lymphocyte non-Hodgkin lymphomas. Other antibody-based treatments may be used for other lymphoma types.

You might be given chemotherapy and monoclonal antibodies at the same time. This is sometimes called chemoimmunotherapy.

CAR-T cell therapy is a specialised treatment in which a person’s own T cells are modified in a laboratory to recognise lymphoma cells. It may be used for some relapsed or refractory (meaning non-responsive to standard treatment) B-cell lymphomas.

Radiotherapy uses radiation to destroy cancer cells. It’s usually given using a large machine that aims radiation to the specific part of your body where the lymphoma is. Radiation is usually used for early-stage lymphoma that hasn’t spread.

Other therapies include steroids and cancer growth blockers.

HIV treatment should be taken as normal during your treatment for lymphoma. It will make your immune system stronger and can help keep the cancer under control. If you are not already taking HIV treatment, you are strongly recommended to start. Your doctor should check that there are not any drug-drug interactions between your lymphoma and HIV treatments.

Treatment for the lymphoma as well as the cancer itself can lower your levels of white blood cells (a condition called leucopenia). This makes you more at risk of dangerous infections. Your doctors and nurses can explain what signs of infection to look out for and what to do if you think you have an infection. You may also be given other treatments to reduce your risk of infections.

Like any other treatment, cancer treatments can have side effects which can sometimes be unpleasant. Each treatment has different side effects and it’s important to ask about the potential side effects of the specific treatment that is suggested for you. For example, not all chemotherapy drugs make your hair fall out. You may be given additional medications to counteract side effects.

In some cases (such as nausea from chemotherapy), highly effective treatments to limit side effects are now available. If side effects become too severe, your doctors may need to adjust one of the treatments.

There can be drug-drug interactions between cancer treatments and HIV treatments. For this reason, it may be necessary to make some adjustments to your HIV treatment or your cancer treatment.

Because of these issues, it's very important that the doctors treating your cancer and your HIV work together. There should also be contact between the pharmacists in the cancer and HIV clinics. 

A multi-disciplinary team will make recommendations about your treatment. This team may include a haematologist (a doctor who specialises in treating blood cell disorders), an oncologist (a doctor who specialises in treating cancer), a radiologist (a doctor who interprets the results of scans or provides radiotherapy), and a pathologist (a doctor who examines tissue for cancer cells). You will be supported by a cancer specialist nurse during your cancer journey. In case you experience side effects from the treatment or the cancer itself, supportive care can relieve pain and other symptoms and help you maintain the best possible quality of life.

Information and support

For more information, you may find these two organisations helpful:

• Macmillan Cancer Support. You can also contact their helpline team on 0808 808 0000.
• Lymphoma Action. Their helpline team is available on 0808 808 5555.