Overview of anaplastic large cell lymphoma (ALCL)
Peripheral T-cell lymphoma (PTCL) are a group of aggressive (fast growing) T-cell non-Hodgkin lymphomas (NHL). They account for 7% of all non-Hodgkin lymphoma (NHL) cases and 10% of all lymphoma cases.
Anaplastic large cell lymphoma (ALCL) is a rare aggressive (fast-growing) subtype of PTCL. ALCL develops from white blood cells called T-lymphocytes (T-cells). ALCL accounts for about 1% of all NHLs and around 10% of all T-cell lymphomas.
The subtypes of ALCL are:
- Systemic ALCL – ALK positive
- Systemic ALCL – ALK negative
- Breast implant associated ALCL
- Primary cutaneous ALCL
Why is it called ALCL?
It is called anaplastic large cell lymphoma (ALCL) because when the cells are looked at under the microscope, the lymphoma cells look large, undeveloped and very abnormal (known as ‘anaplastic’). There is also a protein found on the surface of the lymphoma cell that is called ‘CD30’, which is the hallmark of the disease.
ALCL can occur in 4 different forms depending on which part of the body is affected. They are either systemic or cutaneous ALCL.
Who is affected by anaplastic large cell lymphoma (ALCL)?
The causes of anaplastic large cell lymphoma (ALCL) are mostly unknown. Very rarely, breast implants are linked to ALCL called ‘breast implant associated anaplastic large cell lymphoma’.
People of all ages can be affected by ALCL, however there are certain subtypes that are more common in different ages.
Symptoms of ALCL
The most common first sign of ALCL is a painless lump that is slowly growing in the neck, armpit or groin that is caused by the swelling of the lymph nodes due to the presence of the lymphoma. For some patients, this swelling may be uncomfortable if the lymph node is pressing on an area of the body causing pain. Other symptoms may include:
- Painless swelling or lump, mainly in the neck, groin or armpit
- Loss of appetite
- Shortness of breath
- Stomach or abdominal discomfort or pain
- Rash (in cutaneous ALCL the appearance of solitary or multiple raised, red skin lesions that do not go away. Tend to ulcerate and itch.)
B symptoms are what doctors call the following symptoms and can include:
- Night sweats (drenching sleepwear & bedding)
- Persistent fevers
- Unexplained weight loss
- Itchy body
It is important to tell the doctor about all as it can determine the type of treatment and when to start.
Types of anaplastic large cell lymphoma (ALCL)
There are 4 main types of anaplastic large cell lymphoma (ALCL) that can be divided into either systemic or cutaneous type.
- Systemic ALCL – ALK positive: This subtype is the most common type of ALCL and is fast growing lymphoma. In ALK-positive ALCL, the abnormal T-cells have a genetic change (mutation). This means they make a protein called ‘anaplastic lymphoma kinase’ (ALK) and are called ALK positive. It usually affects children and young adults, and often those in the 30 years old age bracket. It affects males three times more commonly than females.
- Systemic ALCL – ALK negative: This is an aggressive (fast-growing) subtype that accounts for around 3% of all ALCL cases. Patients do not make the ALK protein and are called ALK negative and mainly affects older adults, mostly around 40-65 years of age. This subtype is more common in men than in women.
- Breast implant associated ALCL: is an indolent (slow-growing) T-cell lymphoma that develops very rarely following silicone breast implantation (‘implants’). This can particularly occur with textured implants rather than the smooth type implants. Although it develops in the breast, it is not a type of breast cancer. Scientists think that it might be caused by an inflammatory reaction to the implant.
- Primary cutaneous ALCL: this subtype is an indolent (slow growing) most commonly present in people aged 50-60 years of age and is rare in children. It is 2-3 times more common in men than in women.
Diagnosis and staging of ALCL
A biopsy is always required for a diagnosis of ALCL. A biopsy is an operation to remove a lymph node or other abnormal tissue to look at it under the microscope by a pathologist to see what the cells look like. The biopsy can be done under local or general anaesthetic depending on what part of the body is being biopsied.
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.
Staging of ALCL
Once a diagnosis of ALCL is made, further tests are required to see where else in the body the lymphoma has affected or located. This is called staging. The staging of the lymphoma helps the doctor determine the best treatment for the patient.
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 is also referred to ‘localised’. Stage 1 or 2 means that the lymphoma is found in one area or a few areas close together.
- Advanced stage means that the lymphoma is stage 3 or 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.
What is the ‘grade’ of lymphoma?
Lymphomas are also often grouped as either indolent (slow growing) or aggressive (fast growing). The grade is also referred to as the clinical behaviour of the lymphoma. ALCL is a high- grade lymphoma.
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.
Prognosis of ALCL
Alk-positive ALCL tends to respond well to chemotherapy and patients often achieve a long-term remission. Most patients with ALK-negative ALCL respond to treatment as well, but the disease is more likely to relapse (come back) within 5 years.
Treatment of ALCL
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.
- 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
Before treatment is started it is important that adequate information is provided about the treatment that is planned, the possible side effects and what to expect. Education from the cancer nurses prior to receiving treatment, can be extremely helpful and should include instructions about becoming unwell or needing medical or nursing assistance.
Systemic ALCL treatments are similar to what can be used for other aggressive lymphomas. Many patients with ALCL will achieve a lasting remission (no lymphoma detected) with combination chemotherapy. Standard first-line treatments can include:
- CHEOP or CHOP (combination chemotherapy of cyclophosphamide, doxorubicin, etoposide, vincristine and prednisolone)
- Stem cell transplant
- Steroid therapy
- Clinical trial participation
Breast implant associated ALCL
Patients who have breast implant associated ALCL often have the implant and any lumps or fluid removed by surgery. This might be the only treatment needed. Patients are then followed up and monitored to make sure all of the lymphoma has been removed. If the lymphoma is more widespread (advanced), chemotherapy may be needed, usually CHOP.
Primary cutaneous ALCL
Primary cutaneous ALCL may go into spontaneous remission (the disease goes away without treatment). If no spontaneous remission occurs or the disease relapses the most common treatment includes:
- Radiotherapy or surgery to remove the area of the skin affected.
- Chemotherapy is only used in patients who have extensive involvement that cannot be treated with localised therapy.
Common side effects of treatment
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
Some treatments for lymphoma can reduce fertility and this is more likely with certain chemotherapy protocols (combinations of drugs) and high-dose chemotherapy used before a stem cell transplant. Radiotherapy to the pelvis also increases the likelihood of reduced fertility. Some antibody therapies may also affect fertility, but this is less clear.
The doctor should advise on whether fertility may be affected or whether fertility preservation should be done before the start of treatment.
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 ALCL
After treatment, many patients can have a period of remission (no signs of lymphoma or when the lymphoma is under control). In some patients the lymphoma comes back (relapses) or in rare cases does not respond to the initial treatment (refractory).If this happens there are other treatments that can be successful and can include:
- Brentuximab Vedotin
- Combination chemotherapy
- Targeted therapy
- Brentuximab vedotin (Adcetris)
- Stem cell transplant
Treatment 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 ALCL. Current treatments that are being investigated include:
- Brentuximab Vedotin (Adcetris)
- Pralatrexate (Folotyn)
What happens after treatment?
Sometimes a side effect from treatment may continue or develop months or years after treatment has completed. This is called a late effect.
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.