Overview of classical Hodgkin lymphoma (cHL)
Hodgkin lymphoma (HL) is potentially an aggressive (or fast growing) B-cell lymphoma. HL is characterised by the presence of very large cells called Reed-Sternberg (RS) cells, although other abnormal cell types may be present.
HL is divided into two main types, classical HL which accounts for 90 – 95 percent of cases and the remainder are Nodular Lymphocyte Predominant HL. It is important that the exact subtype of HL is known at diagnosis so that the correct treatment is started for the patient.
Types of classical Hodgkin lymphoma Chl
There are four subtypes of classical Hodgkin lymphoma (cHL). They are named after the appearance of the lymphoma cells and the cells surrounding them under the microscope. They include:
Nodular Sclerosis Classical Hodgkin Lymphoma (cHL): this is the most common subtype accounting for about 60-80 percent of all Hodgkin lymphoma cases. It affects women more than it does men. This subtype receives its name from its appearance under the microscope with nodular referring to a ‘node-like’ pattern in the tissue and sclerosis referring to ‘scar tissue’ as there is typically a mixture of Reed-Sternberg cells, normal white blood cells and scar tissue.
Mixed Cellularity Classical Hodgkin Lymphoma (cHL): accounts for approximately 15–30% of all cHL cases. This subtype is more common in men than women and typically affects older adults.
Lymphocyte depleted classical Hodgkin lymphoma (cHL): is the rarest subtype accounting for less than 1% of cHL cases. It occurs more commonly in HIV-infected or EBV-infected patients. This subtype frequently occurs in the bone marrow (up to 75% of cases). It is rarely diagnosed.
Lymphocyte rich classical Hodgkin lymphoma: accounts for less than 5 percent of all cHL cases. This subtype of cHL is typically diagnosed at an earlier stage than other subtypes of cHL and has a very low relapse (comes back) rate. It is difficult to differentiate this subtype from nodular lymphocyte predominant HL as they have a similar presentation and prognosis.
Who is affected?
Classical Hodgkin lymphoma (cHL) affects both males and females equally. Classical HL is most common in the 15 -29 age group with a second peak later in life in over 70 years of age. Although it can occur at any age.
Scientists do not know exactly what causes cHL, although there are different risk factors that may be associated. Some risk factors may include:
- Epstein-Barr virus (EBV): around 40% of cHL cases are related to a past infection with EBV. EBV is a very common virus that can cause glandular fever. EBV infects B lymphocytes. Around 9 in 10 adults have been infected with EBV at some stage, but for many people it may not cause any symptoms. The EBV infection stays in the body but it is kept under control by the immune system.
- Immune system problems
- Human Immunodeficiency Virus (HIV) infection
- Chemical exposure to solvents, certain pesticides and fertilizers
- Family history: lymphoma is not an inherited or contagious condition and you cannot pass it to family members but there may be a slightly higher risk of developing lymphoma if a close relative was diagnosed with it.
It is important to note that these are only risk factors and many people do not develop HL.
Symptoms of classical Hodgkin lymphoma (cHL)
Usually the first sign of HL is a painless, rapidly growing lump in the neck, arm pit or groin. These lymphoma nodes do not go away after a few weeks. The lymph nodes are usually painless, however sometimes swelling may be painful if the lymph node is pressing on a sensitive area (nerve or blood vessel). They rarely start outside of the lymph nodes.
Classical Hodgkin lymphoma can also cause swollen lymph nodes inside the chest area. This can cause a cough, breathlessness or it may not cause any symptoms at all. Due to the swollen lymph nodes Hodgkin lymphoma can occasionally become painful a few minutes after drinking alcohol. This is not common, but it can be a strong sign of Hodgkin lymphoma.
Note: it is important to remember that lymph nodes can swell for lots of reasons including an infection.
Other common symptoms may include:
- Fatigue (tiredness and lack of energy)
- Shortness of breath (lymphoma may be around chest area)
- Loss of appetite
B symptoms can occur in around 25% of patients and can include:
- Night sweats (drenching sleepwear & bedding)
- Persistent fevers (greater than 38C)
- Unexplained weight loss (>10% normal body weight over the past 6 months or less)
- Itchy skin
- Pain in the lymph nodes after drinking alcohol (even a small amount)
A biopsy is always required for a diagnosis of lymphoma. A biopsy is a surgical procedure to remove part of or all of an affected lymph node to be send to a pathologist. The biopsy can be done under local or general anaesthetic depending on what part of the body is being biopsied. The biopsy can be one of three ways:
- Fine needle aspirate
- Core needle biopsy
- Excisional node biopsy
An excisional node biopsy is the best investigative option, as it collects the most adequate amount of tissue to be able to do the necessary testing for a diagnosis.
Waiting for test results can be a difficult time. It may help to talk to your family, friends or a specialist cancer nurse.
Once a diagnosis of classical Hodgkin lymphoma (cHL) is made, there are further tests that are required to see where else in the body the lymphoma has affected or is located. This is called staging. The staging of lymphoma helps the doctor to determine the best treatment.
There are four stages from stage 1 (lymphoma in one area) through to stage 4 (lymphoma that is widespread).
- Early stage means stage 1 and some stage 2 lymphoma. This may also be referred to as ‘localised’. Stage 1 or 2 means that the lymphoma is found in one area or a few areas close together.
- Advanced stage means the lymphoma is stage 3 and stage 4, and it is widespread lymphoma. In most cases, the lymphoma has spread to parts of the body that are far from each other.
Staging scans and tests
The scans and tests needed for staging and before treatment can start may include:
- Positron emission tomography (PET) scan
- Computed tomography (CT) scan
- Bone marrow biopsy
- Lumbar puncture & magnetic resonance imaging (MRI) – If lymphoma is suspected in the brain or spinal cord
Patients may also undergo a number of baseline tests prior to any treatment commencing to check organ functions. These are often repeated during and after the treatment has completed to assess whether the treatment has affected the functioning of organs. Sometimes the treatment and follow-up care may need to be adjusted to help manage side effects. These may include:
- Physical examination
- Vital observations (blood pressure, temperature, & pulse rate)
- Heart scan
- Kidney scan
- Breathing tests
- Blood tests
It may take some time for all the necessary biopsies and tests to be done (an average of 1-3 weeks), but it is important for the doctors to have a complete picture of the lymphoma and the general health of the patient in order to make the best treatment decisions
Many of the staging and organ function tests are done again after treatment to check whether the lymphoma treatment has worked and the effect this has had on the body.
It is important to note that lymphoma is what is known as a systemic cancer. It can spread throughout the lymphatic system and nearby tissue and organs. Many patients can be diagnosed at an advanced stage, but Hodgkin lymphoma can still be cured.
What is the ‘grade’ of lymphoma?
Lymphomas are also often grouped as either indolent or aggressive. Indolent lymphomas are usually slow growing and aggressive lymphomas are fast growing. The grade is also referred to as the clinical behaviour of the lymphoma. Hodgkin lymphoma is a high-grade lymphoma.
Prognosis for classical Hodgkin lymphoma (cHL)
Classical Hodgkin lymphoma is usually treated with the aim to cure. cHL usually responds very well to standard first-line treatment, where almost 90 percent of patients achieve a complete metabolic response (CMR) or go into remission (no sign of detectable lymphoma).
Treatment for classical Hodgkin lymphoma (cHL)
Once all the results from the biopsy and the staging scans have been completed, the doctor will review these to decide the best possible treatment for a patient. At some cancer centres, the doctor will also meet with a team of specialists to discuss the best treatment and this is called a multidisciplinary team (MDT)meeting.
Doctors take into consideration many factors about the lymphoma and the patient’s general health to decide when and what treatment is required.
This is based on:
- The stage of lymphoma
- Symptoms (including the size and location of the lymphoma)
- How the lymphoma is affecting the body
- Past medical history & general health
- Current physical and mental wellbeing
- Patient preferences
Classical Hodgkin lymphoma (cHL) is a rapidly growing lymphoma, and treatment will need to start within a few weeks after a diagnosis is made. The standard treatment for patients with cHL is a combination of chemotherapy drugs and some patients may also receive radiotherapy after the chemotherapy has completed. There are two standard first-line chemotherapy regimen options that your doctor may recommend depending on the factors that are listed above. These can include:
Stage I-IIIA (favourable) classical Hodgkin lymphoma:
- ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine): These chemotherapy agents are administered into a vein with all of the listed medications being administered in one day. Chemotherapy is repeated on Day 1 and Day 15 of a 28-day cycle for 4-6 cycles.
Stage IIB-IV (unfavourable) classical Hodgkin lymphoma:
- Escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisolone): this chemotherapy regimen is administered over multiple days (Day 1, 2, 3 & day 8 day) in a 21-day cycle for 4-6 cycles.
- Clinical trial participation
Common side effects
There are many different side effects of the treatment and these are dependent on the treatment that has been given. The treating doctor and/or cancer nurse can explain the specific side effects prior to the treatment. Some of the more common side effects of treatment may include:
- Anaemia (low red blood cells carry oxygen around the body)
- Thrombocytopenia (low platelets that help bleeding and clotting)
- Neutropenia (low white blood cells help with immunity)
- Nausea and vomiting
- Bowel problems such as constipation or diarrhoea
- Fatigue (tiredness or lack of energy
The medical team, doctor, cancer nurse or pharmacist, should provide information about:
- What treatment will be given
- What are the common and possible side effects for the treatment
- What side effects do you need to report to the medical team
- What are the contact numbers, and where to attend in case of emergency 7 days a week and 24 hours per day
Once treatment has completed, post treatment staging scans are done to review how well the treatment has worked. The scans will show the doctor if there has been a:
- Complete response (CR or no signs of lymphoma remain) or a
- Partial response (PR or there is still lymphoma present, but it has reduced in size)
If all goes well regular follow-up appointments will be made for every 3-6 months to monitor the below:
- Review the effectiveness of the treatment
- Monitor any ongoing side effects from the treatment
- Monitor for any late effects from treatment over time
- Monitor signs of the lymphoma relapsing
These appointments are also important so that the patient can raise any concerns that they may need to discuss with the medical team. A physical examination and blood tests are also standard tests for these appointments.
Apart from immediately after treatment to review how the treatment has worked, scans are not usually done unless there is a reason for them. For some patient’s appointments may become less frequent over time.
Relapsed or refractory classical Hodgkin lymphoma (cHL)
Classical Hodgkin lymphoma usually responds very well to chemotherapy, but in some patients the lymphoma comes back (relapses) after a period of remission or in rare cases does not respond to the initial first-line treatment (refractory). Second-line treatments can work well and can include:
- Salvage chemotherapy (high dose combination chemotherapy) followed by an autologous stem cell transplant ( own stem cells)
- Salvage chemotherapy (high dose combination chemotherapy) followed by an allogeneic stem cell transplant (donor)
- Combination chemotherapy
- Immunotherapy: including pembrolizumab (Keytruda) or brentuximab vedotin
- Clinical trial
If a relapse is suspected often the same staging exams are done, which include the tests that were stated above in the staging section.
Treatments under Investigation
There are many treatments that are currently being tested in clinical trials around the world and in Australia for patients with both newly diagnosed and relapsed lymphoma. Some of the treatments that are currently being investigated in clinical trials for relapsed or refractory classical Hodgkin lymphoma include:
- Bendamustine (RibomustinTM)
- Brentuximab vedotin (AdcetrisTM)
- Gemcitabine (GemzarTM)
- Chimeric antigen receptor (CAR) T-cell therapy
- LAG 3 inhibitor with pembrolizumab (KeytrudaTM)
What happens after treatment?
Sometimes a side effect from treatment may continue or develop months or years after treatment has completed.
This can be a challenging time for many people and some of the common concerns can be related to:
- Mental wellbeing
- Emotional health
- Work, study, and social activities
Health and wellbeing
A healthy lifestyle, or some positive lifestyle changes after treatment can be a great help after the treatment has been finished. Making small changes such as eating and increasing fitness can improve health and wellbeing and help the body to recover. There are many self-care strategies that can help during the recovery phase.