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Mantle cell lymphoma
Mantle cell lymphoma is a type of non-Hodgkin lymphoma. It is a cancer of the
lymphatic system, which is part of our immune system. In this information sheet
we aim to answer some of the questions that people diagnosed with mantle cell
lymphoma might have:
• What is mantle cell lymphoma? (see below)
• Who gets mantle cell lymphoma and why? (page 3)
• What are the symptoms of mantle cell lymphoma? (page 3)
• What tests can I expect to have? (page 3)
• How is mantle cell lymphoma treated? (page 5)
• What happens when mantle cell lymphoma comes back? (page 8)
• What new treatments may be available in the future? (page 8)
What is mantle cell lymphoma?
Mantle cell lymphoma is not a common
Figure 1: The lymphatic system
type of lymphoma – about 500 people are
diagnosed with it each year in the UK. Many
people have never even heard of lymphoma
Neck (cervical)
before, so first we will explain what
lymphomas are and about the different types. lymph nodes
Lymph vessels
What are lymphomas?
Lymphomas are cancers that develop
when lymphocytes (a type of white blood
cell) grow out of control. Lymphocytes
usually fight infections and often collect in
our lymph nodes (glands), which act like
sieves in our lymphatic systems. When we
have an infection such as a sore throat, our
bodies make more lymphocytes. These
may collect in our lymph nodes, making
them swell until the infection has gone.
Armpit (axillary)
lymph nodes
Groin (inguinal)
lymph nodes
Thymus
Diaphragm
(muscle that
separates the
chest from
the abdomen)
Spleen
Liver
Lymph nodes are found in many areas of
the body: some are easily felt if they are
enlarged (swollen); others are deep inside
us and will only be seen on scans.
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A lymphoma forms when some of the lymphocytes in the body become abnormal.
These abnormal lymphocytes grow more quickly or do not die off when they should.
They start to collect in large numbers, often building up in lymph nodes and making
them swell. The abnormal lymphocytes may collect in other places too, such as the
bone marrow, spleen or bowel (gut). Lymphoma that forms in these areas, outside of
lymph nodes, is called extranodal lymphoma.
What kinds of lymphoma are there?
There are two main types of lymphocytes, known as B and T lymphocytes (or just
B cells and T cells). Most non-Hodgkin lymphomas, including mantle cell lymphoma,
develop from abnormal B lymphocytes, so they are called B-cell lymphomas.
Non-Hodgkin lymphomas are also divided into high-grade (fast growing) lymphomas
and low-grade (slow growing) lymphomas.
What is different about mantle cell lymphoma?
Mantle cell lymphoma was described only quite recently, in 1992. It is called ‘mantle
cell’ lymphoma because the abnormal lymphocytes come from part of the lymph node
called the ‘mantle zone’. This makes up the outer layer of areas in the lymph node
known as follicles.
Figure 2: A lymph node
At first it was thought that mantle cell lymphoma would be slow growing because it
looks like a low-grade lymphoma under the microscope. In fact, it usually grows quickly
and behaves more like a high-grade lymphoma. We now know that it differs from other
lymphomas in many more ways too.
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One of the key things is a change in the genes of the lymphoma cells. Scientists can
see that two of the chromosomes (chromosome 11 and chromosome 14) have broken
and then joined up with each other to produce what is called a ‘translocation’. This
translocation means the cells make too much of a protein (cyclin D1) that is involved in
controlling cell growth. Too much cyclin D1 causes uncontrolled growth, so many new
cells are made and a mantle cell lymphoma develops.
Who gets mantle cell lymphoma and why?
Mantle cell lymphoma is more than twice as likely to develop in a man as in a woman. It
usually occurs in people who are older, most often in people in their mid-60s.
The cause of mantle cell lymphoma is not known but it is important that you know:
• You have not done anything to yourself to cause lymphoma.
• You did not inherit it from your parents, nor are your children likely to get it.
• You did not catch it and you cannot pass it on to others.
What are the symptoms of mantle cell lymphoma?
Possibly the first thing you will have noticed was one or more swollen glands that
probably didn’t hurt but didn’t go away. Often other areas are affected too by the
time mantle cell lymphoma is diagnosed. This means you might have lots of different
symptoms, depending on which areas of your body the lymphoma is affecting.
For instance, lymphoma in the bone marrow can stop enough normal blood cells
being made. If this happens, you may become anaemic (short of red blood cells),
which might make you feel very tired or short of breath. Or you might notice you are
bruising easily or bleeding because of a lack of platelets. Sometimes large numbers
of lymphoma cells are released from the bone marrow into the bloodstream. If this
happens, you won’t notice anything yourself, but the lymphoma may show up on a
routine blood test.
It is quite common for mantle cell lymphoma to cause bowel problems, such as
diarrhoea. Sometimes this can be the first symptom, so to start with the lymphoma
might be mistaken for a bowel condition. Even people with no bowel symptoms
usually have mantle cell lymphoma in their bowel wall if specialised tests are done to
look for it. Other areas that can be affected include the liver, spleen and tonsils.
What tests can I expect to have?
Tests will be done for two reasons:
1 to make a definite diagnosis
2 t o see what areas of your body the lymphoma is affecting and work out its 'stage'
(see page 5).
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How is mantle cell lymphoma diagnosed?
Mantle cell lymphoma is usually diagnosed by taking a biopsy of an enlarged lymph
node or another abnormal area. It can be hard to make the diagnosis because the
cells can look like other types of lymphoma under the microscope. Further tests
looking at changes in the genes and proteins of the cells are needed to make a
definite diagnosis. Because of this, in the UK most lymphomas are now diagnosed in
specialist laboratories and by expert lymphoma pathologists.
Other tests to find out more about your lymphoma
If you have been diagnosed with mantle cell lymphoma, you will need more tests to
check which areas the lymphoma is affecting.
Other tests you might have include:
• Blood tests
– to check for anaemia or other low blood cell counts
– to check that your kidneys and liver are working well
– to give information on how your lymphoma may behave
–to look for infections such as hepatitis, which could flare up with lymphoma
treatments.
•
Bone marrow test. This involves taking a small sample of your bone marrow
through a needle that is put into the back of your pelvis, just above your hip. The
area is numbed with a local anaesthetic but you may still feel some discomfort.
• Scans, which could include:
–computed tomography (CT) scan, which uses X-rays to create an image of your
internal organs and lymph nodes
–magnetic resonance imaging (MRI) scan, which may give better images of some
parts of the body
–positron-emission tomography (PET) scan, a relatively new test, which is still
being assessed in mantle cell lymphoma.
There is no need to specifically examine the bowel if you do not have bowel
symptoms. This is because in most cases finding mantle cell lymphoma in the bowel
will not change your treatment.
These tests are usually done when you are an outpatient. It may take a couple of
weeks for all the results to be ready. It’s normal for you to worry while waiting for
these tests and results, but your doctors need to have all the information before they
plan your treatment.
For more information about tests for lymphoma please ring our helpline
(0808 808 5555).
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What does the stage of a lymphoma mean?
The ‘stage’ of your lymphoma shows which parts of your body have been affected. The
doctors work this out from the results of the scans and other tests.
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
Lymphoma is found in organs outside of the lymph nodes and spleen
* a sheet of muscle that separates the chest from the abdomen (see figure 1 on page 1)
Most people with mantle cell lymphoma will have stage III or IV lymphoma by the time
they are diagnosed. This means their treatment must work on the lymphoma in all
areas of the body rather than in just one area. This is why radiotherapy (treatment with
high doses of X-rays) is rarely used to treat mantle cell lymphoma.
How is mantle cell lymphoma treated?
Mantle cell lymphoma is difficult to cure but treatments are improving all the time.
Doctors are learning more from new clinical trials about how best to treat mantle cell
lymphoma.
A few people with mantle cell lymphoma have a type that grows quite slowly, the
so-called indolent form. In this form, lymphoma cells are often seen in the bloodstream
but lymph nodes are small or do not grow rapidly. If you have this type of mantle cell
lymphoma, your doctors may suggest waiting to start treatment until your symptoms
become troublesome. This is known as the watch-and-wait approach – it is often used
for people with low-grade lymphomas.
For more information about watch and wait for lymphoma please ring our helpline
(0808 808 5555).
More often mantle cell lymphoma grows quickly, so it needs to be treated like a
high-grade lymphoma. This means most people with mantle cell lymphoma will have
intravenous chemotherapy (chemotherapy given into a vein).
In a small number of people, the mantle cell lymphoma grows very quickly – this
is known as the 'blastic variant'. However, all types of mantle cell lymphoma tend
to relapse (come back) quite quickly after treatment. For these reasons, doctors
sometimes suggest people with mantle cell lymphoma have stronger treatment. This
could mean having a different chemotherapy regimen or following the chemotherapy
with a stem cell transplant.
The treatment that is chosen for you will depend on how your lymphoma is behaving,
your age, your general health and your feelings about the treatment.
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Chemotherapy
The standard treatment for high-grade lymphoma, which is often used for mantle
cell lymphoma, is CHOP. This is made up of four drugs: three given intravenously –
cyclophosphamide, hydroxydaunorubicin, vincristine (Oncovin®) – and steroid tablets
– prednisolone – taken by mouth. The treatment is usually given once every 3 weeks
in a day-care unit.
Although mantle cell lymphoma may go into remission with (be controlled by) CHOP,
it isn’t cured and often relapses quite quickly. Clinical trials suggest that stronger
treatments can delay the relapse of mantle cell lymphoma. However, such treatments
cause more side effects and can be given only to inpatients. As a result, these
treatments will suit only a small number of people with mantle cell lymphoma. If you
are young and fit enough, your doctor may suggest trying a stronger chemotherapy
regimen.
One drug that seems to be an important part of any stronger treatments is
cytarabine (also known as Ara-C). This must be given intravenously in a high dose.
It is sometimes combined with other drugs or it can be given on its own, between
cycles of CHOP. One combined regimen sometimes used is DHAP, which is made up
of dexamethasone, high-dose Ara-C and cisplatin (Platinol®).
There are many other chemotherapy drugs and regimens that are used to treat mantle
cell lymphoma – new treatments are becoming available all the time. One new drug
that is likely to be used more in mantle cell lymphoma is bendamustine. This is given
intravenously in a day-care unit on two consecutive days each month. Clinical trials
suggest it may work as well as CHOP but have fewer side effects.
If you are less fit, your doctors may worry about the side effects you could get with
the regimens we have mentioned so far. They may suggest instead that you have
gentler chemotherapy, with tablets such as chlorambucil or cyclophosphamide.
These may control your lymphoma for a while and can often help ease symptoms.
They should have few side effects and you will probably need to visit the outpatient
clinic only.
Sometimes cyclophosphamide is combined with another drug usually given as a
tablet, known as fludarabine. Given together, these two drugs are stronger than
other oral regimens – more like CHOP – but can have more side effects too.
For more information about chemotherapy, how it is given and coping with its
side effects please ring our helpline (0808 808 5555).
Antibody therapy
Most chemotherapy for mantle cell lymphoma is now combined with the antibody
therapy rituximab (MabThera®). Clinical trials have shown that people with mantle
cell lymphoma do better when they are treated with both antibody and chemotherapy.
Rituximab is currently given intravenously, but in the future it may instead be given
subcutaneously (by an injection just under the skin). It is usually given at the start of
each chemotherapy cycle – a letter ‘R’ is added to the name of the regimen to give
R-CHOP, R-bendamustine or R-DHAP for instance.
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Trials have also shown that older people with mantle cell lymphoma do better when
treated with maintenance rituximab too. This means that rituximab is given on its
own, usually once every 2–3 months after the combined treatment has finished.
Doing this aims to ‘maintain’ the remission (keep the lymphoma under control for
longer) and it is often done for people with low-grade lymphoma.
For more information about antibody therapies such as rituximab please ring our
helpline (0808 808 5555).
Stem cell transplants
Stem cell transplants are now being used more often in people with mantle cell
lymphoma – stem cells are special cells from the bone marrow that can make
normal blood cells. When you have a stem cell transplant you first have high doses
of chemotherapy (and sometimes radiotherapy) to kill off the lymphoma cells. This
treatment causes lots of damage to your bone marrow, so that without extra help it
might never recover. The help comes from a transplant (or transfusion) of stem cells
that will make your bone marrow work again.
The stem cells used in a transplant may be your own, taken earlier in your treatment,
or may come from a donor. This gives two types of transplant that can be used in
mantle cell lymphoma:
• an autologous stem cell transplant (using your own stem cells)
• an allogeneic stem cell transplant (using cells from a donor).
Stem cell transplants carry lots of risks as well as benefits – they are not suitable for
everyone. If your doctors are thinking about this form of treatment for you, they will
talk to you in detail about it.
Autologous transplants
This type of transplant is very unlikely to cure your mantle cell lymphoma but it will
probably give you a longer time in remission. Clinical trials have suggested that giving
strong chemotherapy followed by an autologous transplant leads to very good results
in those who are fit enough for the treatment.
Allogeneic transplants
This type of transplant can offer the chance of cure, but it is more risky, with a chance
of future long-term problems. In recent years, more people with lymphoma have been
treated with reduced-intensity conditioning (RIC) allogeneic transplants (sometimes
called a ‘mini-allo’). These are safer treatments but they still offer many of the benefits.
Clinical trials are now looking at how useful such transplants are for people with mantle
cell lymphoma. Even though they are safer, these transplants are not an option for
people who have other health problems and most are still done in younger patients.
For more information about stem cell transplants please ring our helpline
(0808 808 5555).
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What happens when mantle cell lymphoma comes back?
Mantle cell lymphoma will relapse (come back) after treatment in most people. The
treatment you will have at this stage will depend on:
• the type of treatment you have already had and how well you coped with it
• how well your treatment worked and how long you have been in remission
• how your lymphoma is affecting you now
• your age, general health and your thoughts about further treatment.
Some types of chemotherapy, particularly the gentler treatments, can be used again,
although they may not work as well or for as long second time around. If you are fit
enough, you may be offered stronger treatment, possibly even a transplant if you
haven’t already had one. For a few people, their mantle cell lymphoma grows back
slowly and doesn’t cause any problems at first. If this applies to you, your doctors may
suggest holding off on further treatment for a while (the watch-and-wait approach).
As mentioned before, new drugs are becoming available to treat lymphoma all the time.
These new drugs have often been used in other lymphomas or blood cancers already.
Doctors still need to know how well they work for people with mantle cell lymphoma,
or they may want to know which drugs are best given together. Therefore, you may be
offered the chance to take part in a clinical trial.
You can read more about taking part in trials in our booklet Clinical trials. Please
ring our helpline (0808 808 5555) if you would like a copy.
What new treatments may be available in the future?
The following are some of the newer treatments that may be used for mantle cell
lymphoma. Some of these can be used only in clinical trials; others are already licensed,
meaning they can be used outside of a trial when funding is available.
Bortezomib (Velcade®)
This drug is what is known as a ‘proteasome inhibitor’. This means it works by blocking
the ‘proteasomes’ in the lymphoma cells. Proteasomes break down proteins that help
to control what happens in the cells and how the lymphoma grows. When the proteins
can’t be broken down, the cells no longer work properly, so they die.
The drug is given intravenously or subcutaneously (by injection just under the skin) in a
day-care unit. It is usually given once or twice a week but is very quick to give each time.
Bortezomib is often used in the UK for the blood cancer myeloma. It is already licensed
for people with mantle cell lymphoma in the USA. In Europe it is still mainly being used
in trials, usually combined with other drug regimens such as CHOP or steroids and
rituximab.
Temsirolimus (Torisel®)
This is the only drug currently licensed specifically for treatment of people with mantle
cell lymphoma in Europe. It works by interfering with the chemical messages that
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tell the lymphoma cells to grow. It is given intravenously once a week in a day-care
unit. Only about a third of people with mantle cell lymphoma will improve with this
treatment. Although it is licensed, it has not been approved by NICE (National Institute
for Health and Clinical Excellence) and is not routinely funded in the UK.
Lenalidomide (Revlimid®)
This drug is related to thalidomide, a drug that causes serious birth defects if given to
pregnant women. Both drugs have already been used to treat people with myeloma but
lenalidomide has fewer side effects. A number of trials have looked at using lenalidomide
in people who have already been treated for mantle cell lymphoma. The early signs look
promising – perhaps up to half of people improving with treatment – but more results
from trials are awaited.
Lenalidomide is given as capsules that are taken at home on a number of days each
month. It must not be given to a woman who could be pregnant. It is unclear how
lenalidomide works in mantle cell lymphoma.
Ibrutinib
This drug works by blocking messages in the lymphoma cells that help to keep the
cells alive. It has shown some striking early results for treatment of some types of
lymphoma. Trials are now looking to see what effect it has in people who have already
been treated for mantle cell lymphoma. It is taken by mouth and seems to have
relatively few side effects
A final note
Although mantle cell lymphoma was only quite recently described as a separate type
of lymphoma, doctors now understand a lot more about it. New treatments mean
that people diagnosed with mantle cell lymphoma will now live longer than they
would have done a few years ago. Treatments still need to improve further however,
and will probably be different from those used for other types of lymphoma. These
new treatments need to be proven in clinical trials. You might like to ask your doctor
whether there is a suitable trial for you to take part in. You can find more information
about clinical trials for people with mantle cell lymphoma on the Plymouth Mantle Cell
Lymphoma Trials Unit website (see page 10).
Acknowledgement
We are grateful to Professor Simon Rule, consultant haematologist at Derriford
Hospital, Plymouth, for his help in reviewing this version and writing earlier versions
of this information sheet. Professor Rule chairs the NCRN Mantle Cell Lymphoma
trial group and runs a trials unit in Plymouth specifically for patients with mantle cell
lymphoma. He often sees patients referred to him from other centres in the UK and
advises them on their treatment options.
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Useful sources of further information about mantle cell lymphoma
Mantle Cell Lymphoma Trials Unit
 01752 437513
 via website
www.mantlecelllymphoma.co.uk
Cancer Research UK
 0808 800 4040 (Monday–Friday, 9am–5pm)
 via website
www.cancerhelp.org.uk
Leukaemia & Lymphoma Research
 020 7504 2200 (Monday–Friday, 9am–5pm)
[email protected]
www.leukaemialymphomaresearch.org.uk
Macmillan Cancer Support
 0808 808 0000
 via website
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.
Geisler CH, et al. Nordic MCL2 trial update: six-year follow-up after intensive
immunochemotherapy for untreated mantle cell lymphoma followed by BEAM or
BEAC + autologous stem-cell support: still very long survival but late relapses do
occur. British Journal of Haematology, 2012. 158: 355–362.
Kirschey S, et al. Relapsed and/or refractory mantle cell lymphoma: What role for
temsirolimus? Clinical Medicine Insights: Oncology, 2012. 6: 153–164.
Kluin-Nelemans HC, et al. Treatment of older patients with mantle-cell lymphoma.
New England Journal of Medicine, 2012. 367: 520–531.
McKay P, et al. Guidelines for the investigation and management of mantle cell
lymphoma. British Journal of Haematology, 2012. 159: 405–426.
Zaja F, et al. Salvage treatment with lenalidomide and dexamethasone in relapsed/
refractory mantle cell lymphoma: clinical results and effects on microenvironment and
neo-angiogenic biomarkers. Haematologica, 2012. 97: 416–422.
Inwards DJ, Witzig TE. Initial therapy of mantle cell lymphoma. Therapeutic Advances
in Hematology, 2011. 2: 381–392.
Ondrejka SL, et al. Indolent mantle cell leukemia: a clinicopathological variant
characterized by isolated lymphocytosis, interstitial bone marrow involvement, kappa
light chain restriction, and good prognosis. Haematologica, 2011. 96: 1121–1127.
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How we can help you
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(9am–6pm Mondays–Thursdays; 9am–5pm Fridays) or  [email protected]
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a website with forums – www.lymphomas.org.uk
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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 on this article. 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
Updated: October 2013
Next planned review: 2015
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