In contrast, the
classic low-grade lymphoma is this disorder
of follicular lymphoma. The molecular biology
of follicular lymphoma is fascinating. This
tumor carries a specific translocation the
t(14:18) translocation and that involves the
gene bcl-2. I do not know if you know but
bcl-2 is one of the most important genes within
an oncology and it regulates apoptosis, it
stops the B cell from dying. The name itself
comes from B-cell lymphoma #2. This disorder is
often seen in older patients and they can
be very slowly progressive. CT scans again
are critical in showing the extent of disease,
but treatment may only be given if the disorder
was causing clinical problems because this
is something that is very difficult to eradicate.
Treatment depends on the stage of disease.
Most patients with asymptomatic disease can proceed with observation only.
Aggressive treatment does not prevent transformation to a more aggressive lymphoma such as diffuse large B cell lymphoma.
For stage one, radiation is offered if all involved sites can be contained within a radiation field with minimal toxicity.
For stage 2, 3, or 4 disease that is symptomatic, rituximab plus chemotherapy is used.
This means if there are B symptoms, symptomatic bulky nodal or extranodal disease,
or cytopenias due to bone marrow infiltration, then treatment is indicated for the alleviation of symptoms.
Management is with bendamustine plus rituximab, one of the CD20 monoclonal antibodies, or “R-chop”
which is rituximab plus cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone.
Rituximab as a single-agent is an acceptable alternative in patients with comorbid conditions
that make them poor candidates for chemotherapy and for those with a low tumor burden or slowly progressive disease.
Let me talk
about the third major subtype
of non-Hodgkin lymphoma, mantle cell lymphomas.
The mantle zone is an area of B cells around
germinal centers and follicles of B-cells.
It is a less common lymphoma, but here we
see a particular protein called cyclin D1,
which is overexpressed because of a characteristic
translocation in this disorder. This can be
quite a challenging disease to treat, but
combination chemotherapy can be affected and
what is interesting is that the tablet, which
blocks BTK, the Bruton's tyrosine kinase molecule
is proving very effective in this disorder,
similar to the chronic lymphocytic leukaemia,
but BTK is also finding a very important role.
Another very interesting subtype of non-Hodgkin
lymphoma is lymphoplasmacytic lymphoma. This tends
to occur within lymph node and bone marrow
and that gene MYD88 is mutated in the great
majority of cases very useful for making the
diagnosis and also helping us to understand
the pathogenesis of this challenging disease.
What is interesting about lymphoplasmacytic
lymphomas is they often make an IgM paraprotein.
That is an antibody, but they make it very
high levels and of course it is a clonal antibody.
For this reason, this disorder used to be
known as Waldenstrom macroglobulinemia and
indeed it is often used for that term still
to this day. Now, The problem with the IgM
paraprotein is that it can cause a number
of clinical problems. IgM is a very big antibody
and that makes the blood quite viscous difficult
for the heart to pump around the body. On
the right, you will see some retinal hemorrhages
and the patient who have a high IgM level
within that blood and the treatment of this
disorder again is within combination chemotherapy
and CD20 specific antibodies. Sometimes in
the early stage of the disease, we actually
have to take plasma of patients with lymphoplasmacytic
lymphomas to lose some of those IgM antibodies
to give the patient some relief before the
chemotherapy starts to work. Burkitt lymphoma
again is a remarkable subset
of lymphoma with some unique features. It
is a highly aggressive lymphoma. It proliferates
very aggressively and if you look at this
biopsy of this tissue may be 90 percent or
more cells may be trying to divide. It is
characterized by over-expression of myc often
through that specific translocation of t(8:14)
and on the right you will see a map of Africa.
Now we have used that because Burkitt lymphoma
is often seen in children who live in Africa
particularly in malarial regions and here
it is triggered by EBV infection. So we have
two infectious complications, EBV and malaria
coming together causing genetic damage and
leading to Burkitt lymphoma. Elsewhere across
the world, we do see Burkitt lymphoma.
We call those sporadic cases and sometimes EBV
is involved in these cases as well.
Burkitt lymphoma is also more common in people carry
HIV infection. The Burkitt lymphoma is an
aggressive disease. It needs urgent treatment,
but intensive chemotherapy now is allowing
us to cure most patients with Burkitt lymphoma
and is one of the great success stories of
chemotherapy within lymphoma. I said earlier
on that 15 percent of non-Hodgkin
lymphoma are all T-cell origin. These are
less common and some more what more difficult
to treat, but I have just chosen to pick up
four these subtypes and I explained a few
things about these now. On the top left, cutaneous
T-cell lymphoma. This is a disorder in which
the malignant T-cells . . . to the skin and
cause a range of clinical problems in the
skin. This includes mycosis fungoides and
Sezary syndrome. This is a difficult disorder
to treat and some therapy is needed to be
skin directed or can be given as
intravenous chemotherapy. On the top right is a group
of disorders called peripheral T-cell lymphomas,
which presents similarly to diffuse large
B-cell lymphomas and highly difficult to treat
and cure. On the bottom left are anaplastic
lymphomas. These are interesting because they
tend to express ALK protein and there is a
drug that can inhibit that protein and be
used in these disorders and finally in the
bottom right a rare subset of disease called
adult T-cell leukaemia/lymphoma. This is seen
in people from Japan or areas of the Caribbean
and is particularly important and interesting
because this is driven by infection by retrovirus
called HTLV-1 and those in the past world
in which virus is quite common.
So In summary, we have learned in this lecture
that Hodgkin lymphoma defined by the Reed-Sternberg
cell is now highly treatable and the therapy
really aims to minimize damage to the patient
from intensive chemotherapy. We can use PET
scans that help us to approach that.
As you have seen, there are many subtypes of non-Hodgkin
lymphoma defined by histology and increasingly
by the genetics and in the lecture, we have
looked at most of the major subtypes of non-Hodgkin
lymphoma and thus I hope I have given an impression
to you treatments are improving in most areas
although unfortunately only a minority of
cases remain curable at the current time.
I hope you find this as a useful lecture.