Overview of adult T-cell leukaemia-lymphoma (ATLL)
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.
Adult T-cell leukaemia-lymphoma (ATLL) is a rare and often very aggressive (fast-growing) T-cell non-Hodgkin lymphoma. ATLL is a subtype of PTCL. ATLL can be found in the blood, lymph nodes, skin and other areas of the body.
ATLL is linked to the viral infection, HTLV-1 (human T-cell lymphotropic virus 1). ATLL only affects people who have the HTLV-1 virus. This virus is common in Japan, China, the Caribbean, central and South America, Iran, Romania and parts of Africa.
Chronic and smouldering indolent (slow growing) subtypes of ATLL are incurable. These patients often have a better outlook than the more aggressive subtypes of ATLL.
Why is it called leukaemia-lymphoma?
Adult T-cells are found in the peripheral circulating areas of the body (leukaemia), in the lymph nodes or both. The involvement of a gland called the thymus gland and the bone marrow are common and this is where the term leukaemia-lymphoma comes from.
It can be a very confusing disease because it gets tangled up with terms that are similar in other subtypes of lymphoma such as acute lymphoblastic lymphoma and acute lymphoblastic leukaemia.
Who is affected by adult T-cell leukaemia-lymphoma? (ATLL)
It is slightly more common in men than women and can occur from young adulthood through to old age. The average age of onset is 55 years of age.
ATLL is linked to the viral infection, HTLV-1 (human T-cell lymphotropic virus 1). This virus is transmitted through breast feeding to infants, blood transfusions and through sexual intercourse among adults. It has been associated with ATLL and other chronic inflammatory diseases.
ATLL only affects people who have the HTLV-1 virus. This virus is common in Japan, China, the Caribbean, central and South America, Iran, Romania and parts of Africa.
Types of adult T-cell leukaemia-lymphoma (ATLL)
There are four subtypes of ATLL, that are rare in countries such as Australia and North America. It is more prevalent in countries where infection with HTLV-1 is common such as Japan, China, the Caribbean, Central and South America and West Africa.
- Acute ATLL (leukemic) is an aggressive (fast growing) subtype of ATLL. Symptoms develop rapidly and may include fatigue, skin rash and enlarged lymph nodes in the neck, underarm or groin. The main features of acute ATLL are a high white blood cell count of abnormal white cells in the blood (called leukemic). These symptoms are often with elevated calcium levels in the blood (called hypercalcaemia), which can cause irregular heart rhythms and severe constipation. Acute ATLL accounts for around 3 in every 20 cases of ATLL (15%).
- Lymphomatous (lymphoma- type ATLL) is an aggressive (fast growing) lymphoma that accounts for around 13 in every 20 cases of ATLL (65%). It is called lymphoma-type because you have abnormal white blood cells in the lymphatic system but not in your blood. Symptoms may include fatigue, skin rash and enlarged lymph nodes of the neck, armpit or groin.
- Chronic ATLL is an indolent (slow growing) lymphoma that accounts for 3 in every 20 cases of ATLL (15%). It is called ‘chronic’ as it develops slowly over a long time. Chronic ATLL can result in elevated lymphocytes in the blood, enlarged lymph nodes, skin rash and fatigue. It can also be found in other areas of the body such as the spleen and liver.
- Smouldering ATLL is an indolent (slow growing) type of ATLL. Causes 1 in every 20 (10%) cases of ATLL. This subtype is associated with very mild symptoms such as a few skin lesions.
Symptoms of adult T-cell leukaemia-lymphoma (ATLL)
The type of symptoms experienced will depend on the type of ATLL and the location of the lymphoma.
Chronic ATLL and smouldering ATLL are indolent (slow growing) lymphomas. They usually cause mild symptoms such as:
- A skin rash
- Swollen lymph nodes
- A swollen liver or spleen
- High numbers of lymphocytes in the bloodstream
Acute ATLL and lymphomatous are aggressive (fast-growing) lymphomas. Symptoms develop very quickly and can include:
- Swollen lymph nodes
- A swollen liver and spleen (may cause a bloated and painful abdomen)
- Skin rash
- Itchy body
- High levels of calcium in the blood which can cause sickness, diarrhoea, constipation, headaches, urinating more frequently or feeling thirsty and tired.
B symptoms are what doctors call the following symptoms and can include:
- Night sweats (drenching sleepwear & bedding)
- Persistent fevers
- Unexplained weight loss
Diagnosis of ATLL
A biopsy may be required for an ATLL diagnosis. 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.
A blood test will be necessary to measure the white blood cell count and calcium levels and to test for exposure to HTLV-1 virus.
Waiting for results can be a difficult time and it may help to talk to family, friends or a specialist nurse.
Staging, scans and tests
Staging is not used for ATLL, because it is spread throughout the body when first diagnosed. There is a system to classify ATLL as high- risk, standard or low-risk. Most cases of ATLL are classed as high-risk.
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.
Grade of the lymphoma
It is important to know the grade of the lymphoma to help the doctor determine the best treatment for the patient. Some of the tests needed can include:
- Positron emission tomography (PET) scan
- Computed tomography (CT) scan
- Bone marrow biopsy (in some people but not all)
- Blood test
Prognosis of ATLL?
Acute and lymphomatous adult T-cell leukaemia-lymphoma (ATLL) often require urgent treatment due to the aggressive behaviour of the disease. Patients diagnosed with ATLL can have a poorer prognosis.
Patients usually achieve remission (no signs of cancer detected) after the initial first-line treatment of chemotherapy but often relapse soon after treatment. There are currently many research studies for ATLL and these trials are looking at better ways to treat and improve outcomes.
Chronic and smouldering indolent (slow growing) subtypes of ATLL are incurable. These patients often have a better outlook than the more aggressive subtypes of ATLL. These subtypes may have periods of ‘watch and wait’ or treatment to keep the disease under control. These subtypes may need chemotherapy if they become more aggressive.
Treatment of adult T-cell leukaemia-lymphoma (ATLL)
Once all of the results from the biopsy and the staging scans have been completed, the doctor will review these to decide the best possible treatment for the 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 doctors will take into consideration many factors about the lymphoma and general health of the patient to decide when and what treatment is required. This is based on:
- The stage and grade of your lymphoma
- Age, past medical history & general health
- Current physical and mental wellbeing
- Personal preferences
The standard first-line treatment for ATLL can include:
- CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone)
- CHOEP (cyclophosphamide, doxorubicin, vincristine, etoposide and prednisolone)
- Dose- adjusted EPOCH (etoposide, vincristine, doxorubicin, cyclophosphamide and prednisolone)
- Hyper-CVAD (cyclophosphamide, vincristine, doxorubicin and dexamethasone) alternating with high dose methotrexate and cytarabine
- Stem cell transplantation may be appropriate following remission in some patients
- Clinical trial participation
Other treatments may include medications to treat the underlying HTLV-1 virus infection. This may be effective in patients with slower-growing forms of ATLL with mild or no symptoms, that include:
- ‘Watch and wait’ (active monitoring)
- Topical steroids
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 to occur with certain treatments. These may include some 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 if fertility may be affected and whether to have fertility preservation done. This 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 management of ATLL
ATLL usually responds well to Immunochemotherapy, but in some patients the lymphoma comes back (relapses) or in rare cases does not respond to initial treatment (refractory). There are other treatments that can be successful, and these treatments can include:
- DHAP (dexamethasone, cytarabine and cisplatin)
- ESHAP (detoposide, methylprednisolone, cytarabine and cisplatin)
- GDP (gemcitabine, dexamethasone and cisplatin)
- ICE (ifosfamide, carboplatin and etoposide)
Treatments under investigation
There are many treatments that are currently being investigated in clinical trials around the world and in Australia for patients with both newly diagnosed and relapsed ATLL. These include:
- Belinostat (Beleodaq)
- Bortezomid (Velcade)
- Brentuximab Vedotin (Adcetris)
- Lenalidomide (Revlimid)
- Mogamulizumab (Poteligeo)
- Nivolumab (Opdivo)
- Pralatrexate (Folotyn)
- Romidepsin (Istodax)
- High-dose chemotherapy followed by allogeneic stem cell transplantation (patients stem cells from a donor)
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.