Burkitt’s lymphoma
By Dr Salim Amour
What is Burkitt’s lymphoma?
Burkitt’s
lymphoma is a type of high-grade non-Hodgkin lymphoma that develops from B lymphocytes (B cells).
It is one of the fastest growing lymphomas. This means though that it is more
likely to be cured by treatment than many other types of lymphoma.
Burkitt’s
lymphoma is named after a doctor called Denis Burkitt’s. He first wrote about a
form of this lymphoma after seeing children and young adults with it in Africa.
The kind of Burkitt’s lymphoma he described is now called ‘African-type’ (or ‘endemic’) Burkitt’s lymphoma. Another kind (the
‘sporadic’ type) is more often seen
in the Western world.
Who gets Burkitt’s lymphoma?
Burkitt’s
lymphoma is not common: only 1 in every 30–50 people with a B-cell
non-Hodgkin lymphoma will have this type of lymphoma.
Both
children and adults can be affected by Burkitt’s lymphoma (sporadic type). It
makes up over a third of all the lymphomas seen in children. It is quite common
in adolescents and young adults too. The number of people over 60 who are
diagnosed with this type of lymphoma is also increasing.
Men
and boys are more likely to get Burkitt’s lymphoma – more than two-thirds of
adults with Burkitt’s lymphoma are men.
What causes Burkitt’s lymphoma?
The
endemic (African) type of Burkitt’s lymphoma is almost always linked to a
previous infection with the Epstein–Barr virus (EBV). This is the virus that
causes glandular fever.
In
the type of Burkitt’s lymphoma seen in the UK – the sporadic type – the role of
EBV is less certain. EBV is a common virus: blood tests show that 9 out of 10
adults in the UK have had this infection at some time in their life. It is not
clear why a few people develop lymphoma while most do not.
Although
this lymphoma is sometimes linked to a virus, it is important that
you know:
Ø You cannot catch lymphoma.
Ø You did not inherit it from your parents.
Ø You cannot pass it on to others.
Having
a weakened immune system also makes some people more likely to develop Burkitt’s
lymphoma. For example, this might affect people with HIV (human immunodeficiency virus) infection.
Most
patients with Burkitt’s lymphoma will not have HIV infection, but everyone
should have a blood test to rule this out. It would be very important to treat
the HIV infection as well as the lymphoma if it was found.
What are the symptoms?
The
symptoms of Burkitt’s lymphoma often come on over just a few weeks because the
lymphoma cells are dividing so quickly. For the same reason, many people have
this lymphoma in several places by the time it is diagnosed.
You
will probably have:
Ø Swelling of one or more groups of lymph nodes in
different parts of your body.
You may also have:
Ø Abdominal pain, sickness and/or diarrhea – Burkitt’s
lymphoma commonly affects the bowel
Ø A very swollen abdomen caused by a collection of fluid
within your abdomen (called ‘ascites’)
Ø More serious bowel problems such as bowel obstruction or
bleeding from your bowel
Ø lymphoma in an extra nodal site (outside the lymphatic
system) – this is common, involving organs such as the liver, kidneys,
ovaries and breasts – symptoms will depend on the site
Ø other symptoms of lymphoma, including
o
drenching sweats, especially
at night
o
tiredness or fatigue
o
fever and flu-like
symptoms, and
o
loss of appetite and
weight loss
Ø low blood counts due to lymphoma in the bone marrow – this
is common in Burkitt’s lymphoma and can lead to
o
anaemia, causing shortness of breath
and tiredness
o
low platelets, making you more
likely to bleed or bruise very easily
Ø lymphoma cells seen on a blood sample when looked at under
the microscope
Ø lymphoma in your brain and spinal cord (known as your
‘central nervous system’ or CNS), which can cause many different symptoms
including
o
headache
o
seizures
o
confusion
o
inability to concentrate.
In
children with the endemic type, Burkitt’s lymphoma often affects the jaw. It
seems to grow in the areas where the permanent teeth are forming. This rarely
happens in the sporadic (Western) type.
Tests for Burkitt’s lymphoma
Burkitt’s
lymphoma is usually diagnosed by a biopsy of
a swollen lymph node or another affected tissue. In a few people, Burkitt’s
lymphoma will be found first in the bone marrow or
in tissues removed for other reasons – in this case, lymphoma may not have been
suspected before.
Wherever
the biopsy comes from, it will be examined by an expert pathologist to
make the diagnosis. Other specialist laboratory tests on the biopsy may include
looking for:
Ø specific proteins on and within the cells
Ø changes within the genes of
the cell – in Burkitt’s lymphoma, a gene known as MYC changes
position and overworks, which makes the cells divide very quickly.
Ø It is important to identify Burkitt’s lymphoma correctly
because it needs to be treated differently from most high-grade lymphomas.
Ø As well as a biopsy, you will have other tests to find out
more about:
Ø your general health
Ø The stage of your lymphoma – a guide to how many (and which)
areas of your body are affected by the lymphoma.
Ø Most people with Burkitt’s lymphoma will have blood tests,
scans such as a CT scan, MRI scan or PET/CT scan,
a bone marrow test and
a lumbar puncture.
Ø Further tests that are sometimes done can include:
Ø An electrocardiogram (ECG), echocardiogram (often just
called an echo) or MUGA scan to assess how well your heart is working
Ø A 24-hour urine collection to assess how well your kidneys
are working.
Staging of Burkitt’s lymphoma
The
‘stage’ of your lymphoma shows which parts of your body have
been affected.
There
are four stages, which are written with Roman numerals as stage I to
stage IV. Your doctors will use one of two ways to work out the stage of
your Burkitt’s lymphoma, either:
·
The Ann Arbor system – the system
used for most other lymphomas, particularly in adults
or
or
·
The St Jude/Murphy staging system –
a system more often used for lymphomas in children.
Stage I
One
site only, which can be either a group
of lymph nodes or an extra nodal site
(unless, for the St Jude/Murphy system, the one site is in the chest or the abdomen – see stages II/III)
(unless, for the St Jude/Murphy system, the one site is in the chest or the abdomen – see stages II/III)
Stage II
Lymphoma
on one side of the diaphragm but
in two or more sites, which may be groups of lymph nodes or extra nodal sites
or a mixture
(Lymphoma in the abdomen that has been completely removed by surgery is also stage II when using the St Jude/Murphy system)
(Lymphoma in the abdomen that has been completely removed by surgery is also stage II when using the St Jude/Murphy system)
Stage III
Lymphoma
on both sides of the diaphragm, whether in groups of lymph nodes or
extra nodal sites
(Lymphoma that started in the chest or alongside the spine and lymphoma in the abdomen that cannot be completely removed by surgery, when using the St Jude/Murphy system, are also stage III)
(Lymphoma that started in the chest or alongside the spine and lymphoma in the abdomen that cannot be completely removed by surgery, when using the St Jude/Murphy system, are also stage III)
Stage IV
Lymphoma
in the bone marrow or in
the central nervous system
(and, for the Ann Arbor system, lymphoma in the liver or in extra nodal sites that are not close to each other).
(and, for the Ann Arbor system, lymphoma in the liver or in extra nodal sites that are not close to each other).
Using
the stage, your doctors will decide whether to treat your Burkitt’s lymphoma as
‘favourable’ or not. Favorable lymphomas are stage I lymphomas (and some stage
II lymphomas) that are not causing a rise in a blood test called ‘LDH’.
If
your doctors use the Ann Arbor system, they will also look at:
·
How much you are able to do (known
as your ‘performance status’),
for instance whether you are up and about and able to carry out light work
·
Whether your lymphoma is in more
than one extra nodal site.
Do
not be alarmed if the doctors do not class your lymphoma as favourable. In
fact, very few adults have favourable Burkitt’s lymphoma. The treatments
usually work well for everybody with Burkitt’s lymphoma, but those with
‘favourable’ disease may need slightly less treatment.
Treatment of Burkitt’s lymphoma
Intravenous chemotherapy
Burkitt’s
lymphoma is always treated with chemotherapy, even if the lymphoma is localized
(early stage). The regimens used for Burkitt’s lymphoma involve:
Ø Several different drugs that target the lymphoma cells in
different ways
Ø Drugs being given on several consecutive days.
This
type of chemotherapy has the best chance of killing most of the lymphoma cells
as quickly as possible. The regimens are typically given intravenously (into a
vein) as an infusion (a drip).
People
having these regimens will need to be inpatients because:
Ø Some of the drugs take several hours to give
Ø You will need lots of fluids in your drip to keep your
kidneys working well
Ø The whole treatment takes several days to give
Ø You will also need lots of tests after having the
chemotherapy to check your kidneys and liver and your blood cell counts.
When
you first start chemotherapy, many of the tests you will have will be done to
look for signs of ‘tumour lysis syndrome’. This happens when lots of lymphoma cells
are killed very quickly and is most likely to occur in very
fast-growing lymphomas.
The
chemicals that were in the lymphoma (tumour) cells spill out into the
bloodstream. The body struggles to get rid of the extra chemicals through the
kidneys and rebalance the salts in the blood. The extra fluids in your drip
help with this, and the blood tests will show if any problems are starting to
develop. Serious problems could occur if the levels of salts in the blood
became very abnormal (these can affect the way the heart and kidneys work) or
if the kidneys were overwhelmed by uric acid (one of the chemicals they need to
get rid of).
Tumour
lysis syndrome is a serious condition, which needs to be prevented if possible
or treated at the first sign. Fortunately, the drug rasburicase (Fasturtec®) can help
if it does occur, or can be given to people at high risk of the condition to
prevent it developing. In a way it should be thought of as a good sign, as it
means the chemotherapy has already killed many of the lymphoma cells.
To
make all this treatment easier, your doctors will probably recommend you have
a tunnelled central
line or possibly a PICC line (peripherally
inserted central catheter).
Other treatments
You
are likely to have many of these treatments too:
Ø Mesna and folinic acid, to protect against some of the side effects of
the chemotherapy drugs used in these regimens
Ø Anti-sickness drugs (antiemetics)
Ø Rasburicase (Fasturtec®) initially and allopurinol in later cycles, to protect against tumour
lysis syndrome
Ø Prophylactic (preventive) antibiotics and antifungal, to
reduce the risks of infection
Intrathecal chemotherapy
In
Burkitt’s lymphoma, treatment that targets the CNS (the brain and spinal cord)
is also needed. You may hear this treatment called ‘CNS-directed therapy’
or ‘CNS prophylaxis’.
Some
intravenous drugs will reach the CNS, but Intrathecal
chemotherapy is another way to get drugs to the brain
and spinal cord. It means giving chemotherapy directly into the cerebrospinal
fluid (the fluid that bathes the brain and spinal cord). Only a few drugs can
be given in this way (most often methotrexate and cytarabine).
Normally
Intrathecal chemotherapy is given during a lumbar puncture.
Sometimes a device called an ‘Ommaya reservoir’ is put in to avoid the need for
lots of lumbar punctures.
Possible chemotherapy regimens
The
exact treatment you have will depend on:
Ø Your general health and usual level of fitness
Ø Whether your doctors class your lymphoma as favourable or
not (as explained in the section on staging)
Ø How well you and your doctors think you will cope with the
likely effects of the treatment.
Ø No matter which chemotherapy regimen you have, your whole
treatment will probably take several months. You should expect to spend days or
even weeks at a time in hospital.
Ø R-CODOX-M is
one regimen that is commonly used for adults in the UK. It is made up of:
Ø rituximab
Ø cyclophosphamide – daily for
5 days
Ø vincristine (Oncovin®)
Ø doxorubicin
Ø methotrexate – given over
24 hours.
Ø Three cycles of R-CODOX-M are usually given to people with
‘favourable’ Burkitt lymphoma. For most people, with less favourable Burkitt
lymphoma, R-CODOX-M is alternated with R-IVAC – usually two cycles
of each.
Ø R-IVAC is
made up of:
Ø rituximab
Ø ifosfamide – daily for 5 days
Ø etoposide (VP-16 or VePesid®) – daily
for 5 days
Ø cytarabine (Ara-C) – for the first
2 days.
Ø R-hyper-CVAD is
another regimen that can be used for Burkitt lymphoma. It is made up of:
Ø rituximab
Ø frequent small doses of (hyperfractionated) cyclophosphamide
– given over 3 days
Ø vincristine
Ø doxorubicin (Adriamycin®)
Ø dexamethasone – as tablets for
4 days.
Ø This combination is alternated with high-dose methotrexate
and cytarabine (given over 3 days). Typically four cycles of each will
be given.
Ø DA-EPOCH-R is another regimen that has been used in trials with
some promising results. It is made up of dose-adjusted:
Ø etoposide – infused continuously over
4 days (with the vincristine and doxorubicin)
Ø prednisolone – tablets
for 5 days
Ø vincristine (Oncovin®) –
infused continuously over 4 days
Ø cyclophosphamide
Ø hydroxydaunorubicin (often called
doxorubicin) – infused continuously over 4 days (in people who are well
enough it may be possible to give this through a portable device as an
outpatient treatment)
Ø rituximab.
Ø In children and adolescents, several different
regimens, which formed part of the LMB96 trial, are combined.
These include:
Ø two cycles of COPADM, made up of
o
cyclophosphamide
o
vincristine (Oncovin®)
o
prednisolone
o
doxorubicin (Adriamycin®)
o
Methotrexate.
Ø This is followed by other chemotherapy regimens, depending
on how advanced the lymphoma is and how it responds to early treatment, such as:
Ø CYVE – cytarabine
and etoposide (VePesid®)
Ø CYM – cytarabine
and methotrexate.
Recently,
trials in young people, who are very likely to be cured, have looked at
reducing treatment wherever possible to limit the long-term side effects.
What are the side effects of chemotherapy?
If
you are having intensive chemotherapy, you may get a number of different side
effects. There are lots of things that can be done to help prevent or relieve
these. Do let people know how you are feeling and ask questions if you don’t
know what is happening. Your hospital team will be there to support you through
your treatment.
The
most common side effects of the kind of chemotherapy usually used for Burkitt’s
lymphoma include:
Ø low blood counts, causing
o
Neutropenia (low white blood cells), making you much more prone to
infections – your hospital team need to know at once if you have any signs
of infection
o
Low platelets, making
you more likely to bleed or bruise very easily – you may need platelet
transfusions to help stop you bleeding or to reduce the risk
Ø Temporary hair loss –
usually starting a couple of weeks after chemotherapy has begun and growing
back from a month or two after it finishes
Ø Fatigue
Ø Peripheral
neuropathy (damage to nerves, especially
in the hands and feet), causing symptoms such as pins and needles, pain
and numbness.
Ø Long-terms side effects (late effects) that might affect
you include:
Ø Reduced fertility
Ø An increased risk of second cancers
Ø Heart disease.
Your
doctors will discuss with you what your risks are and what can be done
to help.
What happens if Burkitt’s lymphoma
comes back?
If
your lymphoma is not in complete remission after your treatment or if it comes
back later (relapses), your doctors may offer you further treatment. What can
be offered will depend on:
Ø what your previous treatment was
Ø how well you coped with your previous treatment
Ø whether you are fit enough for more intensive treatments, which
might include
o
High-dose ‘salvage’ chemotherapy,
which is different from the first treatment you had
o
A stem cell transplant once
your lymphoma has responded again to chemotherapy
o
Your thoughts about further
treatment – your doctors and hospital team will help you to decide what is best
for you.
Less common types of Burkitt’s lymphoma
Intermediate type
Sometimes
a lymphoma appears to be like Burkitt’s lymphoma in some ways and like diffuse large B-cell
lymphoma (DLBCL) in other ways. For example the lymphoma
might look like a Burkitt’s lymphoma under the microscope but not have the usual change in
the MYC gene. The official name doctors give
these is ‘B-cell lymphoma, unclassified, with features intermediate between
DLBCL and Burkitt’s lymphoma’.
Some
of these lymphomas will also have another change in their genes and are known
as ‘double-hit’ lymphomas.
These
lymphomas are not common. Often they will be treated in the same way as typical
Burkitt’s lymphoma.
HIV-associated Burkitt’s lymphoma
Lymphomas
are more common in people with HIV infection. Burkitt’s lymphoma makes up around
1 in 6 of the lymphomas seen in people with HIV. It can occur before the HIV
infection starts to cause much immunodeficiency (weakening of the
immune system).
Treating
lymphoma in people with HIV carries more risk of complications, particularly
infections. However, if the same chemotherapy can be tolerated, it often works
just as well. In addition, a recent trial using a form of DA-EPOCH-R
chemotherapy, with a slightly lower dose for people with Burkitt’s
lymphoma and HIV infection, has reported promising results.
Thank you
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