Dr. Francine Foss, Learning how to Cope with
Lymphoma
December 5, 2010
Welcome to Yale Cancer Center Answers with Dr. Francine Foss and Dr. Lynn Wilson, I am Bruce Barber. Dr. Foss is a Professor of Medical Oncology and Dermatology specializing in the treatment of lymphomas. Dr. Wilson is a Professor of Therapeutic Radiology and an expert in the use of radiation to treat lung cancers and cutaneous lymphomas. If you would like to join the conversation, you can contact the doctors directly. The address is canceranswers@yale.edu andthe phone number is 1888-234-4YCC. This evening Dr. Wilson will interview his co-host, Dr. Foss about her work in the study and treatment of lymphoma. Here is Lynn Wilson.
Wilson
Let's get started by having you tell the audience a little bit
about lymphoma and what it is?
Foss
Lymphoma is actually a malignancy, or tumor, primarily of white
blood cells, and there are two different types of tumors of white
blood cells, one of them is leukemia where the primary problem is
in the bone marrow and the cell circulates it around in the blood
and the other one is lymphoma where the problem is primarily in
white blood cells or lymphocytes that live in lymph nodes and in
other lymphoid tissues in our body. If you think about lymph nodes,
we all know that we have lymph nodes in our neck and under our
arms, in our groin, but we also have lymph nodes in many other
areas of our body as well, including inside our body where we can
even see them and also the spleen is considered to be a lymphoid
organ. So, lymphomas can involve any lymphoid tissue and in
fact, they can also involve nonlymphoid tissue such as the lungs,
the liver, the skin, or other part of the body as well.
Wilson
Does it usually start in a lymphoid tissue or can it start in
another location?
Foss
That's a very good question, Lynn, and often times we do not
actually know where some of these lymphomas start, but very
frequently we do find them in lymphoid tissues. There are
some kinds of lymphomas like lymphoma of the skin for instance,
that we find only in the skin, and we actually never find them in
any other lymph nodes or any lymphoid organ other than the
skin. I would say that they probably can arise in lymphoid
areas as well as non-lymphoid tissues in the body.
Wilson
How common of a problem is lymphoma in the United States?
Foss
It is interesting because lymphoma is now the fifth most common
cancer in the United States in both men and women and the incidence
of lymphoma is rising every year and part of the reason for that is
that we are all living to be older, and as the population ages, the
greater the chances are that you are going to develop lymphoma.
Wilson
Obviously there are a lot of different types of tumors and cancers,
how did you make your career decision to specialize in cancers of
the blood and lymphoma?
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Foss
A lot of my career decision to be interested in lymphoma was
related to the fact that I trained at the National Cancer Institute
and I trained with Dr. Vincent DeVita who is kind of the father of
how we treat lymphoma in the United States today. Dr. DeVita
made some major advances in the treatment of lymphomas that we
still use in the clinic today and also there was a tremendous
amount of research in lymphoma while I was at the National Cancer
Institute.
Wilson
We know that there are some diseases such as lung cancer, where
smoking is clearly related as a cause, are there any causative or
etiologic factor associated with lymphomas?
Foss
That's an interesting question, and I think it is an area that is
still undergoing evolution. We know historically that certain
viruses are associated with lymphoma and in fact, the HTLV-1 virus
was identified from a patient with T cell lymphoma. In
addition, we know that other viruses such as EBV virus, which is
the mono virus, can be associated with the development of lymphomas
and we also know that there is an increased incidence of lymphoma
in patients that have hepatitis. But the other major cause is
immunosuppression, and this is primarily in the setting of patients
that have had organ transplant such as a kidney transplant or liver
transplant. Many of those patients need to be on
immunosuppressive medications and those medications can lead to the
development of lymphoma, and likewise, in patients who have various
kinds of autoimmune diseases and require immunosuppressive
medications, there is an increased incidence of lymphoma as
well.
Wilson
Is that because under normal conditions our own body and immune
system is doing surveillance and keeping ourselves in check and
under control, but if we depress the immune systems, some of the
lymphoid cells will start to grow out of control and cannot be kept
in line?
Foss
That is exactly right Lynn, in fact, the body is constantly
undergoing this process called immune surveillance. There are
constantly cells that are undergoing mutations in our body and our
normal immune system, namely our T cell immune system, is
identifying those cells as cells with mutations and is eradicating
or killing those cells before they can divide and lead to a
cancer. So if you suppress these normal lymphocytes,
primarily these normal T cells by immunosuppressive medications, or
other infections, or other kinds of insults to the system, that
immune surveillance process does not go on and eventually what
happens is that there are cells that can mutate and then those
mutations can go on to develop into tumors, lymphomas, and in some
cases solid tumors as well.
Wilson
How would someone start to be concerned that they might have
lymphoma? What are some of the symptoms that can go along
with this disease?
Foss
One of the major issues with lymphoma, unlike other cancers, is
that many of our patients are actually asymptomatic. There
are two types of lymphoma, there is the low grade or indolent
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lymphoma and there is the aggressive lymphoma, and within each of
those groups there are both T cell and B cell lymphomas, so we
start dividing it into a number of different groups, but generally
speaking, if you think about it in terms of low grade lymphoma and
intermediate or high-grade lymphoma, most of the patients with
low-grade lymphoma do not have symptoms. Many of those
patients will go to a doctor for another reason and the doctor will
feel that they have lymph nodes enlarged, or perhaps there is
something wrong with their blood counts. On a rare instance,
the patient may have a physical exam and the doctor may feel that
the spleen is enlarged. In other cases, patients with
lymphoma may actually find a lymph node themselves, they may find a
bump that has just come up. They may also notice that they
have fatigue and what we call B symptoms. B symptoms would be
feeling tired, having night sweats, losing weight, losing your
appetite, things that basically make you feel not well. If
these things occur for more than a week or two and there is no
other illness going on, then the patient should start to worry a
little bit about what is going on. Now not all those patients
would turn out to have lymphoma and not all patients with lymphoma
have B symptoms, so that is just one indicator that the patient may
have this disease.
Wilson
And these lymph nodes, when they are enlarged, are they
painful?
Foss
Many of these are actually not painful and in fact that's one of
the myths that patients have, that if they have lymph nodes that
swell up, this must be cancer, in fact, not only for lymphoma, but
for other cancer as well, most lymph nodes that are tender are not
actually related to cancer. Many of those are related to
infection. That is not to say it can't be cancer but
generally speaking most lymph nodes associated with lymphoma are
painless.
Wilson
I know it is a complicated discussion, but tell our listeners a bit
about different treatment for lymphoma and the treatments for the
different types of lymphomas.
Foss
The treatment of lymphoma really depends on the type of lymphoma,
and that's an important point because what we really need to do to
make a good treatment decision is we need to identify the specific
subtype of lymphoma and we also need to identify, using various
staging tests, how extensive the disease is. The first thing
is to have a pathologist who can make the right diagnosis and since
we now have low-grade and intermediate-grade lymphomas, we have T
cell and B cell, we have gone further than that and we have a
number of different entities or specific types of lymphoma within
each of those categories and the treatment of each one of those is
slightly different. So the first step would be to get the
right diagnosis and the right subtype of lymphoma, and then the
second step would be to undergo a staging evaluation and staging
basically means identifying where the tumor has spread and in the
case of lymphoma, we would like to get CAT scans or in some cases
we could get a PET scan to look at the lymph nodes, the liver, the
spleen as well as the other organs and we would determine whether
the lymphoma is localized or advanced. Another thing that we would
often times do, because lymphoma tends to go to bone marrow, is
get
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a bone marrow biopsy, and in some cases of lymphoma we also look in
the peripheral blood, we look for the presence of circulating
lymphoma cells and we also look for what we call clonal
rearrangements, which would indicate that perhaps there are cells
in the blood. We do a very careful assessment of the patient
looking at all the different places where lymphoma may have spread
to and then we come up with a stage and then we actually look at
the stage as well as the different subtype of lymphoma. If you want
to think about it in general terms we think about the low-grade
lymphomas and the higher-grade lymphomas and in a low-grade group,
many of those patients actually do not need to be treated.
That is something that is difficult for patients to understand, to
come in and get a diagnosis of lymphoma and be told it has
spread to a couple different areas of your body, but you do not
actually need to be treated for this, and the idea to not treat
patients with low-grade lymphoma really arises from a study that we
did at the National Cancer Institute many years ago where we took
patients with low-grade lymphoma of all stages and we randomized
those patients either to what we call watch and wait where they did
not get any treatment right away, compared to aggressive
chemotherapy and radiation therapy to the various lymph nodes that
were involved. As you might expect, the patients who got the
aggressive treatment had a higher response rate in terms of the
lymph node shrinking, but when we look at the overall survival
there was no difference between the two different groups and so
that lead us to believe that we could actually take these low-grade
lymphoma patients and watch them without giving them aggressive
chemotherapy. I will say that things have changed a lot in
the last 15 years or so since we did that study, because now we
have some other biological therapies for lymphoma and perhaps we'd
think about treating some of those low-grade patients with these
biological therapies.
Wilson
It sounds like in your work, you need to be very cautious and
judicious in these decisions because sometimes the treatment could
be worse than the disease itself.
Foss
Exactly, and often times what happens with a lot of these
aggressive chemotherapy regimens that we use for patients is that
they can cause mutations in cells and patients can then go on to
develop other problems like leukemia, so we know that in patients
who have Hodgkins disease who have been treated with a combination
of radiation and chemotherapy, there is an increased chance of
developing not only leukemia but also other kinds of solid tumors
as well, and so when we think about the approach for lymphoma, we
need to think first about what is the type of lymphoma that we are
dealing with and are we going to cure that patient, and then if we
are not going to cure that patient with our treatment, then we need
to think seriously about the treatment that we're giving and we
need to try to minimize the long term effects of those kinds of
therapies on patients who are going to have the disease for 20
years or 30 years.
Wilson
If I had a lymph node in my neck and my doctor was worried about it
and was concerned about
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lymphoma, tell me about the procedure that a patient might go
through to make that diagnosis. Would I have to be admitted
to the hospital and get an operation or can it be done in the
doctor's office? Do they take cells out of the node, do they remove
the lymph node? What does the patient go through when this
diagnosis is made?
Foss
The absolute best way to make a diagnosis of lymphoma is to
actually take out the lymph node so that the pathologist can look
at the entire lymph node and examine the architecture of all the
different types of cells in the lymph and have adequate tissue to
do all the different special stains and genetic studies that we are
now doing for these patients. However, we do not often times
have that optimal situation. For instance, if you have a node
in your neck, it is pretty easy to just get that lymph node taken
out and that can be done as a surgery procedure in a day.
However, if the only node that we find is deep in your abdomen,
hidden behind your liver for instance, it is going to be really
hard to subject a patient to a big operation to get that lymph node
out, and so sometimes we will do what we call a needle biopsy and
there are two different types of needle biopsies. One of them is a
skinny-needle biopsy where we just get cells, and the other one is
called the core needle biopsy where we actually take a little core
of the lymph node and sometimes that kind of procedure is adequate
to tell us if it is an aggressive or low-grade lymphoma, if it is T
cell or B cell and often times that will give us the information
that we need to proceed with the definitive therapeutic plan.
Wilson
You had mentioned a little about markers in the pathology
laboratory, how does that influence what sort of treatment you
might recommend? Once you have decided T or B cell, what
further pieces of information do you get when you look below the
surface that might guide your recommendations?
Foss
These markers are tremendously important and over the last couple
of years they have become even more important. We have been
able to identify specific surface markers on cells and specific
genes that are mutated, for instance, or translocated genes that we
can detect in these tumor cells that help to subcategorize those
cells and tell us exactly what kind of tumor we are dealing with
and often times that gives us important prognostic information, so
for instance, a patient that has a specific type of marker on the
cell may do worse than another patient with the same disease who
does not have that marker, and that is important information when
we decide about what kinds of treatments in terms of chemotherapy,
radiation, and also even in terms of thinking about a stem cell
transplant perhaps for that patient.
Wilson
We are going to take a short break for a medical minute.
Please stay tuned to learn more information about lymphoma with Dr.
Francine Foss.
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Wilson
Welcome back to Yale Cancer Center Answers. This is Dr. Lynn
Wilson and I am joined by my co-host and guest Dr. Francine
Foss. Today we are discussing lymphoma. Francine, tell
us a little bit about the treatment options that are available for
non-Hodgkin's lymphoma versus Hodgkin's lymphoma and how has that
evolved over the last 20 years to 25 years?
Foss
Most of our patients with lymphoma who are not low grade patients,
but more aggressive patients that need chemotherapy, most of those
patients end up getting what we call multi-agent chemotherapy, so
that means they get three or four chemotherapy drugs at the same
time, and often times this treatment goes on for about six cycles,
or about six months of therapy. In the case of Hodgkin's
disease, we use a regimen called ABVD, which has been shown to be
very effective and in fact cures a significant number of patients
with early stage Hodgkin's disease. In the case of diffuse
large B cell lymphoma, we use a regimen called CHOP and recently we
have added an antibody called rituximab to that regimen. The
rituximab antibody is specifically directed against a particular
protein on the surface of B-cells, namely CD 20, and this is a
monoclonal antibody that will target those cells
specifically. Now the rituximab, as I mentioned, is used in
combination with CHOP for patients that need chemotherapy, but
often times we use the rituximab as a single therapy for patients
with lower grade lymphomas. Again, the ones that we might
have watched and waited before, now that we have this therapy that
does not have many side effects, it is enticing to treat our
patients with this immunotherapy earlier on in the course or their
disease. The other thing that we do is we actually use this
rituximab therapy in some patients after they have finished their
chemotherapy in a maintenance setting as well. I just want to
say a little bit about radiation therapy because we always approach
these diseases from a combined modality point of view. In
other words, we have a lymphoma conference where we present all of
our new cases and
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there are radiation oncologists, pathologists, and medical
oncologist that are present at that lymphoma conference and we
always explore the possibility as to whether the addition of
radiation therapy should be used in an individual lymphoma
patient. I will give you an example of where that might be
relevant. For instance, we saw a patient in a lymphoma conference
today who presented with extensive involvement with a B cell
lymphoma but had a very very large mass in the sinus area and we
felt that certainly chemotherapy was warranted for that patient,
but because of this very large mass we felt that that particular
area may need some additional treatment and so the recommendation
for that patient was to get radiation therapy following the
chemotherapy. It is not unusual for patients with diffuse
large B-cell lymphoma or even Hodgkin's disease who have very large
masses to have the addition or radiation therapy along with their
treatment. So the multimodality approach is very important,
and then the other really important aspect of lymphoma therapy is
the follow-up for patients. I mentioned that some patients
get some treatment in the follow-up periods say with rituximab,
other patients actually go on to stem cell transplant. If
they have a very aggressive disease, particularly patients with
relapse lymphoma, they often times need to have a therapy after
they complete their chemotherapy to prevent the disease from coming
back. That is an important part of our strategy, but I think
the other really important part of our strategy is very careful
follow-up for these patients, because if you look at all patients
with diffuse large B-cell lymphoma, about half of those patients
are going to relapse, and so we need to make sure that we do
physical exams and imaging studies such as scans on a regular basis
at least for the first couple of years and really educate our
patients about what to look for in case there is evidence of a
relapse.
Wilson
You had mention transplant as a potential option for certain
patients, what does transplant mean?
Foss
Transplant comes in two different forms, the autologous, which is
giving yourself your own cells, and the allogeneic, which means
that you get somebody else's cells. When we talk about bone
marrow transplant and stem cell transplant, we are really talking
about different forms of the same thing, it used to be that we got
the cells from the bone marrow by doing multiple different needle
sticks into your bone marrow and aspirate out cells, and those
would be the bone marrow cells that we would give back to the
patient. Now we know that we can mobilize those bone marrow
cells into the peripheral blood by using growth factors and other
kinds of agents, and so now what we do for a donor is we just
stimulate the bone marrow to produce the cells, they go into the
blood and the patient comes in to the blood bank and gets hooked up
to a machine like they are donating blood. That machine takes
the stem cells out of their blood and puts them in a bag, we than
freeze them down and give them back to the patient. With an
autologous transplant, which we do frequently for some of our
aggressive lymphoma patients, we will harvest those stem cells when
the patient is in remission, we will then bring patients into the
hospital and give them a week of high dose chemotherapy and then
give them the stem cells back, and the purpose of that is to allow
us to give very very high doses of chemotherapy to get rid of any
residual lymphoma cells
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that might be left in the body and then give back the patient's own
stem cells so that they can reconstitute their bone marrow.
Wilson
It does sound very complicated and I would think that treatment
recommendations might even be slightly different from hospital to
hospital. Are there guidelines that physicians follow,
consensus statements that folks tend to look after to try to make
sure that recommendations are consistent and as up-to-date as
possible?
Foss
That is also a very important point to bring up because this issue
has been addressed at the national level to establish standards of
care for patients with lymphoma, as well as other cancers, and we
have now what we call the NCCN Guidelines, which are basically a
set of consensus guidelines that direct us as to how we treat
various kinds of cancers. This is particularly important for
lymphoma because when we look across the board at a lot of our
lymphoma subtypes many of these patients are actually curable, so
we are dealing with patients who have a curative disease. It
is very important then to treat them with the correct therapy in
the first line, and so the NCCN Guidelines specifically outline
evidence-based approach to treatment for these lymphomas. They
basically look at all of the big randomized clinical trials that
have been done in the various subtypes of lymphoma and they make
recommendations based on what appears to be the most effective, so
called standard therapy for the different subtypes.
Sometimes, say in the case of T cell lymphoma, for instance, there
really are not well established guidelines and so the NCCN will
make recommendations, they will say for instance there are four
possible treatments that could be used and there is no way of
knowing that any one of these is better than the other, but
nevertheless there is an algorithm for each one of these diseases
identifying what all the possible effective therapies are and what
the recommended therapies are if it a situation where there is one
that is clearly better than the others.
Wilson
Tell us a little bit, Francine, about the different major types of
lymphoma, such as Hodgkin's disease, and perhaps what groups of
patient that might effect, older patients, younger, non Hodgkin's
lymphoma, cutaneous lymphomas, tell us some other details about
those diseases?
Foss
Hodgkin's lymphoma really has two different age peaks, one of them
is young people and the other one is middle-aged people, and
Hodgkin's lymphoma is one of the diseases that we feel that we can
cure many of the patients and so this is a very important disease
to be seen and evaluated in a combined modality setting. Hopefully
the slides will be reviewed by a pathologist and make sure that we
have the correct subtype of disease, and so for Hodgkin's patients
I think the outlook is very good using the conventional treatment
strategies that we have. We also have some new approaches for
Hodgkin's, new antibodies such as the SGN 35, which is a targeted
therapy that specifically binds to a protein on the surface of the
cells. For the B-cell lymphomas, I mentioned the low grade
and the intermediate or high grade lymphomas, in the intermediate
or high grade B
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cell lymphomas, again half of these patients are cured with
chemotherapy and the addition of radiation therapy in some cases,
but half of these patients we expect to cure. It is very
important that those patients get treated correctly, that their
treatments are given on time and that they are monitored closely in
follow-up. In the low grade lymphoma group, that is a disease
that tends to occur over a very long period of time, many of these
patients will live with their disease for years and years and
years. The outlook for these patients is now changing
slightly because we do have a number of new therapies that have
been developed. I mentioned the rituximab antibody but there
also are some other new drug therapies that are developed for
patients with low grade lymphoma, and I think in the future that we
are going to see the outlook of that disease change and hopefully
we will have biological therapies available to treat many of those
patients, and then when you get into the T-cell lymphomas, you get
into a little bit of a conundrum because again there are two
different types of T-cell lymphomas. There are the low grade
T-cell lymphomas that primarily are the ones that occur on the skin
that you and I are familiar with, the patients with CTCL, and then
there are the more aggressive T cell lymphomas that look like
B-cell lymphomas that involve lymph nodes, the liver, the spleen,
and other organs in the body. In general, the T-cell
lymphomas tend to be worse than the B-cell lymphomas. It is
very difficult to cure many of these patients with aggressive
T-cell lymphoma. That is an area where now we have a lot of
research ongoing and interestingly, Lynn, that's been an area where
we had a number of new drugs approved by the FDA over the last
year. We are now starting to make a little bit of progress in
patients with aggressive T-cell lymphoma.
Wilson
What are some other side effects of treatments for lymphoma?
Foss
Many of these drugs that we use cause side effects like loss of
hair, nausea, fatigue, and lowering of blood counts. Many of
the conventional chemotherapy drugs, as I mentioned, are given in
these cycles every three to four weeks. When you start
looking at some of these new biological therapies, the side effect
profile is a little bit different. For rituximab, for
instance, patients actually do not notice any side effects. For
some of the other drugs that we are using, like one of the new
drugs that was FDA approved called romidepsin, which is new class
of drug called HDAC Inhibitor, the major side effects of this drug
are fatigue, nausea, and some diarrhea. So it is completely
different than some of the drugs. There is no significant
change in your blood count and there is no loss of hair.
Another new drug like Treanda that was approved for B cell lymphoma
is a drug that does not have any hair loss and so we can now start
talking to patient's about some of these options and thinking about
lifestyle issues as well as what treatments are effective for some
of these lymphomas in the low grade setting, certainly, where
patients go on and work and the disease does not effect their life
to any significant degree. The choice of these therapies is
really important as it fits in with other factors that the patient
has at that point in time, and hair loss is one of the things that
many of my patients complain about bitterly, it is still an
undesirable side effect that we have to deal with with many of our
chemotherapy drugs.
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Wilson
Take Hodgkin's disease, for example, where we have our traditional
combined modality therapy treatment, chemotherapy plus radiation,
which has been extremely successful for the patients with
Hodgkin's, but we worry about side effects and long term side
effects, leukemia, new cancers perhaps related to the treatment,
and it sounds like there has been some groundbreaking discovery in
terms of trying to work on lowering the chemotherapy dose, and
lowering the radiation dose, and those program's early data
revealed that they look like they are pretty successful. What
are your thoughts about that?
Foss
That is another area that we're striving to make some in-roads in
and that is trying to give the lowest dose of chemotherapy that is
going to be effective and eradicate the tumor, and hopefully spare
patient's some of those side effects. In Hodgkin's disease there
are a number of international studies that are ongoing now, looking
at decreasing the number of cycles of chemotherapy that a patient
needs to receive, and using tests like PET scan to detect when a
patient is having a very good response, so if a PET scan is
negative early in the course of the treatment, perhaps that patient
needs less cycles of therapy than a patient whose PET scan is still
positive say after two cycles of therapy. We are also now looking
at using reduced doses of radiation therapy and reducing the felid
of radiation that we are treating in order to decrease some of
these side effects that patients may have later on.
Wilson
This would reduce side effects during the treatment course, and
perhaps long-term complications that might not take place for 20
years or 30 years, is that correct.
Foss
Exactly, and as a radiation therapist you are aware of the fact
that the risk of secondary cancer such as lung cancer or breast
cancer in patients who have radiation to the chest is associated to
some degree with the amount of radiation that the patient
receives.
Dr. Francine Foss is a Professor of Medical Dermatology specializing in the treatment of lymphoma at the Yale School of Medicine. If you have questions for the doctors or would like to share your comments visit yalecancercenter.org, where you can also subscribe to our podcast and find written transcripts of past programs. I am Bruce Barber and you are listening to the WNPR Health Forum on the Connecticut Public Broadcasting Network.