Angioimmunoblastic T-cell lymphoma Freephone helpline 0808 808 5555

Freephone helpline 0808 808 5555
[email protected]
www.lymphomas.org.uk
Angioimmunoblastic T-cell
lymphoma
Angioimmunoblastic T-cell lymphoma (AITL) is a cancer of the lymphatic system, which
is part of the body's immune system. It is a type of non-Hodgkin lymphoma. AITL is
a rare lymphoma – it is estimated that fewer than 200 people are diagnosed with this
lymphoma each year in the UK.
In this information sheet we aim to answer the most common questions people with
this rare cancer ask:
• What is AITL? (see below)
• Who is affected by AITL and what causes it? (page 3)
• What are the symptoms of AITL? (page 3)
• What tests will I need? (page 4)
• What does the 'stage' mean? (page 5)
• How is AITL treated? (page 5)
• What happens when the treatment is finished? (page 8)
What is AITL?
What is lymphoma?
A lymphoma is a cancer of cells called lymphocytes, which are white blood cells
that normally help the body to fight infections. There are two kinds of lymphocyte,
B lymphocytes (usually just known as 'B cells') and T lymphocytes (T cells). B cells
are made in the bone marrow, which is a spongy tissue found in the middle of some
of our bigger bones. T cells start their life in the bone marrow but they mature in the
thymus, a gland in the chest, behind the breastbone.
Lymphocytes collect in lymph nodes (glands). Lymph nodes are found in groups,
particularly under the arms, in the neck and in the groin. We also have groups of lymph
nodes internally, around our organs. Lymphocytes can also be found in other parts
of the body, such as in the spleen and the thymus. These places are all part of our
lymphatic system (see Figure 1 on page 2).
A lymphoma develops when lymphocytes either live for longer than normal or start
to divide in an uncontrolled way to produce large numbers of new lymphocytes. The
effect is the same – too many lymphocytes accumulate and cause swelling of lymph
nodes or collect in other parts of the body.
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Figure 1: The lymphatic system
Neck (cervical)
lymph nodes
Lymph vessels
Thymus
Diaphragm
(muscle that
separates the
chest from
the abdomen)
Armpit (axillary)
lymph nodes
Spleen
Liver
Groin (inguinal)
lymph nodes
What types of lymphoma are there?
Lymphomas can develop from either type of lymphocyte. There are therefore B-cell
lymphomas and T-cell lymphomas. If a lymphoma develops and grows quickly it is
called a ‘high-grade’ or ‘aggressive’ lymphoma. If it grows slowly it is described as a
‘low-grade’ or ‘indolent’ lymphoma.
There are over 60 types of lymphoma but there are two main kinds, Hodgkin lymphoma
and non-Hodgkin lymphoma. These look different when they are examined under the
microscope. They also affect people differently.
What type of lymphoma is AITL?
AITL is a high-grade T-cell non-Hodgkin lymphoma. It is one of a group of lymphomas
known as the ‘peripheral T-cell lymphomas’. In AITL, T cells become cancerous and
accumulate in lymph nodes and in other tissues such as the bone marrow, liver and
spleen. When samples of affected tissue are examined under the microscope the
pathologist sees small, abnormal blood vessels and immature immune cells called
immunoblasts as well as the cancerous T cells. This is how it got its name ('angio'
means 'relating to blood vessels').
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Who is affected by AITL and what causes it?
AITL is most common in middle-aged and elderly people (around 60–65 is the average
age) and it is slightly more common in men. It is more common in Europe than it is in
North America.
Lymphoma develops when lymphocytes start to grow out of control. This is often due
to a change within the genes of the lymphocytes. This genetic change can mean that
the lymphocytes are not able to control how quickly they divide or die off.
It has been noticed that many people with this lymphoma show signs of having had
an infection with a virus called the Epstein–Barr virus (EBV). It is not clear, however,
whether this virus is causing the genetic changes in the lymphocytes – which then
grow out of control to form a lymphoma – or whether an EBV infection has just been
reawakened in the body because the immune system isn’t working as well as it
should because of the lymphoma. Many people in the population have had an EBV
infection, but very few people develop lymphoma, so there must be other reasons for
the lymphoma developing.
Despite this possible link with EBV infection, it is still not known what causes AITL.
What doctors do know is that nothing you have done – or not done – will have caused
the lymphoma to develop. AITL is not a disease that you can inherit or pass on to your
children.
What are the symptoms of AITL?
Symptoms develop in AITL when cancerous lymphocytes build up in lymph nodes or
in places outside the lymph nodes (extranodal sites). The lymphoma can also affect
how well your immune system works. For example, the immune system might not
protect you properly and you can keep coming down with infections. Or the immune
sysptem can over-react and you can develop symptoms of an infection (such as a
fever) when you don't actually have one. In addition, the cancerous lymphocytes
sometimes produce abnormal proteins that cause your immune system to react
against your normal cells (such as your blood cells) – this kind of reaction is called
autoimmunity.
AITL therefore causes is a wide range of possible symptoms:
•lumps, which are swollen lymph nodes (glands). These are often in several places,
for example in the groin, armpits and neck
•feeling generally unwell, with symptoms similar to those you have when you have
an infection – fever, unexplained weight loss and night sweats (known as
'B symptoms')
•abdominal discomfort and sometimes distension (swelling) caused by cancerous
lymphocytes in the spleen and/or the liver or by a collection of fluid in the abdomen
(this is called 'ascites’)
•difficulty with breathing due to collection of fluid around the lungs (a pleural effusion)
• skin rash, often with itching
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• joint pains
•tiredness or shortness of breath due to a type of anaemia called 'haemolytic
anaemia', which is caused by an autoimmune reaction against red blood cells
•symptoms of infections – infections are more likely to occur and to be more severe
if there is AITL in the bone marrow.
What tests will I need?
There are several different types of T-cell lymphoma and it is important to find out
exactly which type you have and how much it is affecting you. This is so that an
individual treatment plan can be drawn up for you. A biopsy is the only way to make a
diagnosis of AITL. Other tests are then done to find out which parts of your body the
lymphoma is affecting – this is called the 'stage' of the lymphoma.
Biopsy
You will need to have a sample of tissue that is affected by the lymphoma removed
so that it can be sent to the pathology laboratory. You will usually have a whole lymph
node removed after the skin over the node has been numbed with local anaesthetic.
This is called an 'excision biopsy'. Sometimes the biopsy is done after you have had a
general anaesthetic.
The different kinds of lymphoma are recognised by their appearance under the
microscope. The biopsy sample might also need to be sent away for more detailed
tests, sometimes to another laboratory. These tests are done to look at the proteins
on the surface of the lymphoma cell (immunohistochemistry tests) and at the genetic
make-up of the lymphoma cells (cytogenetics tests). The results of these specialised
tests can take around 2 weeks to come back.
Staging tests
In order to assess which parts of your body are affected by AITL, you will have a
physical examination and you will have some or all of these tests:
•
blood tests – to measure the numbers of different blood cells in your sample (the
blood counts), to assess your immune system and to assess how well your liver
and kidneys are working
•
bone marrow biopsy, a test in which a small sample is taken from the bone
marrow in your hip bone using a needle (the skin is numbed with a local
anaesthetic first) to see if the lymphoma is affecting the bone marrrow
• scans:
–computed tomography (a CT scan) of the chest, abdomen and pelvis is the most
usual scan people with AITL will have
–positron-emission tomography (a PET scan) – this type of scan is done in some
centres if the specialist feels it would help them to plan your treatment.
If you would like to talk to someone about your tests, please ring our Freephone
helpline on 0808 808 5555.
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What does the 'stage' mean?
Once the test results are back your medical team will be able to tell what stage your
lymphoma is at. This is what the stages mean:
Stage I
One group of lymph nodes is affected
Stage II
Two or more groups of lymph nodes are affected on one side of the
diaphragm*
Stage III
Lymph nodes are affected on both sides of the diaphragm
Stage IV
There is lymphoma in the bone marrow or in organs that are not part of
the lymphatic system
*A sheet of muscle that separates the chest from the abdomen.
If a 'B' is attached to the stage number this means that you have experienced one or
more of the B symptoms (see page 3). If you haven't had these symptoms there will
be an 'A' attached to the number. An 'E' attached to the stage number means that
there is lymphoma in extranodal sites.
Stage I and stage II lymphomas are described as 'early stage'. A few people with AITL
will be diagnosed at an early stage. Most people will have AITL at a more advanced
stage when they are diagnosed, meaning stage III or IV.
How is AITL treated?
T-cell lymphomas can be quite hard to treat. Research shows that about a quarter to
a third of people with AITL will be successfully treated and will survive for 5 years or
longer.
Even though most people with AITL will have advanced disease by the time it is
diagnosed, this doesn’t mean that it is too late for treatment. What treatment you have
will depend on several factors, including your age and general health. It might also
depend on whether there is a clinical trial you can take part in.
Very rarely, AITL can go away by itself or it can be kept under observation for a while.
Nearly everyone with this lymphoma will need treatment soon after the diagnosis has
been made, however.
A few people can be treated with steroid tablets alone, but AITL is usually treated with
chemotherapy.
Chemotherapy
Chemotherapy is treatment with drugs that kill the lymphoma cells or stop them from
dividing. Sometimes you will be given one chemotherapy drug, but usually you will be
given two or more drugs. This is called ‘combination chemotherapy’. You have the drug
combination over a period of a few days, then have a few weeks without any drugs
(usually about 3 weeks), then have another cycle of treatment.
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The most common combination chemotherapy treatment that is used to treat AITL is:
•
CHOP – a combination of cyclophosphamide, hydroxydaunorubicin and vincristine
(Oncovin®), together with the steroid drug, prednisolone.
Other combination therapies that are given for AITL are:
• FC – fludarabine and cyclophosphamide
• CVP – cyclosphosphamide, vincristine and prednisolone.
Some people might afterwards go on to have treatment with low doses of a
chemotherapy drug called methotrexate, together with prednisolone.
Other chemotherapy drugs that are sometimes given singly to treat AITL are
fludarabine, cladribine and gemcitabine. Gemcitabine might be given in combination
with prednisolone. A combination of gemcitabine, cisplatin and prednisolone is being
used as an initial treatment in a clinical trial that is currently open in the UK (the
Chemo-T trial).
There are several chemotherapy options to choose from because this is a rare
lymphoma and specialists haven’t been able to show yet that any one regimen is
markedly better than any of the others. Which treatment you will have will depend on
what the hospital you are being treated at prefers to use for people with AITL. It will
also depend on whether or not you are taking part in a clinical trial.
Other drugs under investigation for treating AITL
There are several other drugs that have been shown to be effective in treating AITL,
either on their own or together with chemotherapy. These are usually only available if
you are taking part in a clinical trial because they are still being investigated.
An antibody treatment is sometimes given together with or after chemotherapy.
If it is given afterwards this is called ‘consolidation therapy’. Antibodies are proteins
that attach themselves to the cancerous lymphocytes. This attracts other cells of the
body’s immune system to come and destroy and remove the ‘marked’ lymphoma
cells. Antibody treatments that are sometimes given to people with AITL are:
• rituximab (MabThera®)
• alemtuzumab (Campath)
• bevacizumab (Avastin®).
Bevacizumab targets an important molecule that is involved in the formation of new
blood vessels (such as the abnormal vessels that form in AITL) and it is being given
with CHOP in one clinical trial in the United States.
Two other drugs that are known to prevent blood vessel formation that are being used
to treat AITL are:
•thalidomide
•lenalidomide.
Thalidomide in particular can be a good option for people who are not well enough to
have treatment with an intensive chemotherapy regimen.
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Other treatments that are sometimes used to treat AITL are denileukin diftitox
(Ontak®), interferon alpha and ciclosporin. Lastly, there are a few drugs that have
shown some success in treating other T-cell lymphomas that are occasionally used to
treat AITL, such as romidepsin (Istodax®) and vorinostat (Zolinza®).
High-dose chemotherapy and stem cell transplantation
Specialists who treat AITL will be aiming to get the lymphoma into remission with
chemotherapy. Remission means that tests show no sign of the lymphoma. If you are
fit enough and if your lymphoma was sensitive to the chemotherapy drugs, your team
might then want to ‘consolidate’ the remission with high-dose chemotherapy and a
stem cell transplant. A stem cell transplant might also be an option if the AITL comes
back some time after you have gone into remission.
This type of treatment wouldn’t be suitable if your AITL didn’t respond well to the
initial chemotherapy, if there is lymphoma in the bone marrow or if you have had
treatment with fludarabine chemotherapy.
A stem cell transplant is a treatment which allows very high doses of anti-lymphoma
therapy to be given to you. When you have a stem cell transplant you first have
high doses of chemotherapy (and sometimes also radiotherapy). Although this highdose treatment will kill any lymphoma cells that remain in the body after the initial
chemotherapy, it causes so much damage to your bone marrow that it might never
recover by itself. Instead it is ‘rescued’ (helped to recover) by the stem cells that are
transplanted into you.
Stem cells are special cells from the bone marrow that can make normal blood cells.
The stem cells are put into your bloodstream, just like a blood transfusion. They then
settle in your bone marrow where they start to grow and make new blood cells.
The stem cells can come from:
•yourself, collected from your blood before your high-dose chemotherapy – this is
known as an autologous transplant (sometimes called 'stem cell support'); or they
can come from
•a donor (a related donor if possible) – this kind of transplant is called an allogeneic
or 'donor' transplant and is a much more intense form of treatment.
Autologous stem cell transplants are sometimes used to treat people with AITL.
Allogeneic transplants are only occasionally used to treat AITL, usually only in people
whose general health is good enough to withstand this more intense and risky type of
transplant.
If you would like to talk to someone about any aspect of your treatment,
please ring our helpline on 0808 808 5555. We also have separate information
on steroids, chemotherapy, antibody treatments and stem cell transplants.
You can ask the helpline for this or you can download it from our website
(www.lymphomas.org.uk).
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Supportive treatments
Supportive treatments are treatments you are given to help with the symptoms of the
lymphoma and the side effects of the chemotherapy. For example you might be given:
• steroids to help with joint pains, skin rash or abnormalities in your blood counts
• blood transfusions to combat anaemia
• anti-sickness drugs to prevent nausea during chemotherapy
• antibiotics for any infections that develop.
Taking part in a clinical trial
Researchers are continually trying to find out which treatment or combination of
treatments works best for lymphoma. You might be asked to take part in a clinical
research trial. Clinical trials are very important because they allow new treatments to
be evaluated and compared with more established ones. Studying treatments like this
is the only way that new and hopefully better treatments can become available.
When you are enrolled into a clinical trial you can be assured that you will receive
modern and appropriate treatments. Sometimes newer treatments are only available
if you are taking part in a trial. It is always worth asking your consultant if there might
be a trial you could take part in.
You don’t have to take part in a trial if you are offered this, however. If you don’t feel
comfortable with the idea of taking part in a trial after discussing all the options
with your medical team, be assured that you will receive the best current standard
treatment available.
We have a booklet about taking part in clinical trials. If you would like a copy of
this or if you would like to talk to someone about taking part in a trial, please
phone our helpline (0808 808 5555). The booklet can also be downloaded from
our website (www.lymphomas.org.uk).
What happens when the treatment is finished?
Follow-up after your treatment
Once the treatment is finished you will be seen in the outpatient clinic every 1–3 months
at first, then every 6 months after a year or so. Exactly how often you are seen in
the clinic will depend on how you got on with the treatment, your hospital's normal
practice and whether or not you are having treatment as part of a clinical trial. You
might have blood tests and scans done during your follow-up, but they are not done
routinely.
If your symptoms come back, if new symptoms develop or if you feel generally
unwell, however, you can contact your medical team and they will see you early. They
will do another biopsy if they suspect that the lymphoma has come back, and might
also repeat some of the other tests (see page 4).
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What happens if AITL comes back?
It is quite common for AITL to relapse (come back). If the tests show that the AITL
has come back, it can be treated again. Most people with relapsed AITL will be
offered another course of chemotherapy and/or another of the drugs described on
pages 5–7.
If you are well enough and if you responded well to your first course of treatment, the
medical team might discuss the possibility of having high-dose chemotherapy and an
autologous stem cell transplant (see page 7).
You might be able to have treatment with one of the newer drugs that are available
mainly through clinical trials, so ask your medical team if there is a suitable trial for you.
Acknowledgement
The Lymphoma Association is grateful to Professor Stephen Devereux, Consultant
Haematologist at Kings College Hospital NHS Foundation Trust, London, for his help
with reviewing this information
Useful organisations
CancerHelp UK
CancerHelp UK is the patient information website of Cancer Research UK and
provides information on different types of cancer, including lymphomas. The CRUK
website also has a clinical trials section.
0808 800 4040 (Monday–Friday, 9am–5pm)
www.cancerresearchuk.org
Macmillan Cancer Support
Provides practical, medical, emotional and financial help, as well as comprehensive
information on all aspects of cancers, treatments and living with cancer.
0808 808 0000 (Monday–Friday, 9am–8pm)
www.macmillan.org.uk
Selected references
The full list of references is available on request. Please contact us via email
([email protected]) or telephone 01296 619409 if you would like a copy.
Swerdlow SH, et al. WHO Classification of tumours of haematopoietic and lymphoid
tissues. 4th edition. 2008. IARC Press, Lyon, France.
Dearden CE, et al. Guidelines for the management of mature T-cell and NK-cell
neoplasms (excluding cutaneous T-cell lymphomas). British Journal of Haematology,
2011. 154: 451–485. Updated August 2013. Available at: http://www.bcshguidelines.com/
documents/T_NHL_guideline_3_8_13_updated_with_changes_accepted_v1_rg.pdf
(accessed 06 January 2014).
Dunleavy K, et al. New strategies in peripheral T-cell lymphoma: understanding tumor
biology and developing novel therapies. Clinical Cancer Research, 2010. 16: 5608–5617.
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Savage KJ. Therapies for peripheral T-cell lymphomas. Hematoloy / The Education
Program of the American Society of Hematology, 2011. 515–524.
Tang T, et al. Peripheral T-cell lymphoma: review and updates of current management
strategies. Advances in Hematology, 2010. 2010: 624040.
Alizadeh AA, Advani RH. Evaluation and management of angioimmunoblastic T- cell
lymphoma: a review of current approaches and future strategies. Clinical Advances in
Hematology & Oncology, 2008. 6: 899–909.
How we can help you
We provide:
a Freephone helpline providing information and emotional support  0808 808 5555
(9am–6pm Mondays–Thursdays; 9am–5pm Fridays) or  [email protected]
●
●
booklets and other information about lymphoma (free of charge)
●
a website with forums – www.lymphomas.org.uk
●
●
the opportunity to be put in touch with others affected by lymphoma through our
buddy scheme
a nationwide network of lymphoma support groups.
How you can help us
We continually strive to improve our information resources for people affected by
lymphoma and we would be interested in any feedback you might have. Please visit
www.lymphomas.org.uk/feedback or email [email protected] if you
have any comments. Alternatively please phone our helpline on 0808 808 5555.
We make every effort to ensure that the information we provide is accurate but it should
not be relied upon to reflect the current state of medical research, which is constantly
changing. If you are concerned about your health, you should consult your doctor.
The Lymphoma Association cannot accept liability for any loss or damage resulting from
any inaccuracy in this information or third party information such as information on
websites which we link to. Please see our website (www.lymphomas.org.uk) for more
information about how we produce our information.
© Lymphoma Association
PO Box 386, Aylesbury, Bucks, HP20 2GA
Registered charity no. 1068395
Produced: January 2014
Next planned review: 2016
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