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Chemotherapy can be surprisingly effective for this
uncommon cancer in cats.
Introduction
Veterinarians are
keenly aware of the bizarre tendency for uncommon
illnesses to present themselves in “threes”. I was
caught off guard, however, when Katy’s bloodwork arrived
on our printer.
Katy is a 13 year-old
female cat belonging to Michael Thomas and Kama
Sanguinetti. She had a mammary adenocarcinoma removed
some months before, and I had been monitoring her
closely after the surgery, given the malignant nature of
these tumors. Months had gone by with no signs of a
recurrence of her mammary cancer, however, Katy’s
kidneys gradually began to fail, a common, expected
development as cats begin to age. I had been managing
her renal failure, and she seemed to be doing well,
however, her owners felt that she was losing more
weight. Being only 7 pounds to begin with, there wasn’t
much Katy to spare, and a re-examination was clearly in
order. Chronic renal failure is known to cause weight
loss. Was Katy’s kidney failure progressing rapidly,
despite our countermeasures?
On physical
examination, Katy was bright and alert, her striking
yellow-orange coat still nice and shiny. She basically
looked the way she had when I examined her three months
earlier, except for the 1 lb. weight loss. Although one
pound doesn’t sound like a lot, this amounted to almost
15% of her body weight. I suggested we run some tests –
a complete blood count, serum chemistry panel, thyroid
evaluation, and urinalysis – to get a detailed picture
of her current health status. Her owners agreed.
I expected an increase
in her kidney parameters. What I found, however, was a
dramatic increase in the level of protein in her
bloodstream. Protein in the bloodstream is divided into
two major components: albumin and globulins. Katy’s
globulin level was extremely elevated. A few other
parameters were above or below the normal range, but it
was the extreme elevation of the globulin level that was
most worrisome. Although there are several potential
causes for elevated globulins, I had recently diagnosed
a rare cancer in two other cats with similar bloodwork,
and I feared that Katy would complete the triad: I
suspected that she had multiple myeloma.
The globulin story
The main component of
the globulin fraction of the serum is antibodies. It is
not uncommon to see an increased amount of globulins in
the bloodstream when a cat has an infectious condition,
because the immune system typically responds to
infections by increasing production of antibodies.
Antibodies are instrumental in helping to fight off the
infection. A slight increase is expected. A massive
increase, however, is troublesome.
Globulins are produced
by cells of the immune system called plasma cells. When
the immune system is stimulated (for example, by an
infection), a variety of different plasma cells will
react to the stimulus by producing a wide array of
antibodies. This is reflected in the bloodwork as an
elevation in globulins.
Occasionally, and for
no discernable reason, one particular plasma cell may
become cancerous. That plasma cell will multiply, and
multiply, and multiply. This large population of
cancerous plasma cells will produce many identical
copies of the particular antibody it is programmed to
produce. This, too, would be reflected in the bloodwork
as an elevation in globulins. How does one determine if
the increase in globulins is due to non-specific
stimulation of the immune system as if in response to an
infection, or if the increase is due to something more
ominous, like multiple myeloma?
Proving my hunch
Serum protein
electrophoresis is a test that allows the globulins to
be characterized further, by separating them according
to their physical properties. The serum is placed on a
gel, and an electrical current is applied. The
globulins migrate across the gel based on their charge
and size, and a pattern emerges (Figure 1). Albumin, a
serum protein, appears on the left. The next five
components (the globulins) appear and are labeled alpha
1, alpha 2, beta 1, beta 2, and gamma. The gamma
fraction is where the antibodies are found. Figure 1
shows a typical, normal pattern.
(Figure 1)
Infectious and/or
inflammatory conditions will cause an increase in
globulins, and when electrophoresis is performed, the
pattern will still look like that in Figure 1, although
the gamma peak might be a little bit larger.
If, however, the
electrophoresis reveals a very tall, narrow peak in the
gamma region (Figure 2), it suggests that multiple
copies of an identical antibody have been produced by
one particular subset or “clone” of cells. This narrow
peak is called a “monoclonal spike”, meaning one
(“mono”) clone (“clonal”) is responsible for the pattern
seen. The list of diseases that can do this is very
short, and multiple myeloma is at the top of the list.
This is the pattern that I saw when the laboratory ran
the test on Katy’s serum.
(Figure 2)
Diagnosis of multiple myeloma,
however, requires meeting at least two of the
following criteria:
- A monoclonal spike seen on
protein electrophoresis
- Detection of certain proteins,
called Bence-Jones proteins, in the urine
- X-ray evidence of bony lesions
- Presence of cancerous plasma
cells in the bone marrow
We satisfied the first
criterion for Katy: the monoclonal spike. We were close
to making a definitive diagnosis.
Antibodies are
proteins. A closer look at their structure reveals that
antibodies are made up of two large strands or “chains”,
and two small chains. The large strands are called
“heavy chains” and the smaller strands are called “light
chains”. Multiple myeloma cells produce large
quantities of heavy and light chains, which are then
assembled into antibodies. In normal animals, light
chains are not found in urine. In cats and dogs with
multiple myeloma, so many light chains are produced that
they may spill over from the bloodstream into the
urine. In the urine, the light chains are known as
“Bence-Jones” proteins. I sent a specimen of Katy’s
urine to our diagnostic laboratory, asking them to
analyze it for Bence-Jones proteins. The test came back
negative. This did not mean that she did not have
multiple myeloma. It means that we have to move on to
another criterion, and work a little harder to obtain a
definitive diagnosis.
Destruction of bone,
and the pain associated with it, is a fairly common
finding in dogs and humans with multiple myeloma, but
not very common in cats. It is believed that the
cancerous cells produce a substance that activates
osteoclasts – cells that resorb bone. On x-rays, the
affected bones contain small circular lesions, and are
often described as looking as if a “hole-puncher” was
used on them. In dogs, the bones most often involved
include the spine, pelvis, ribs, skull, and proximal
extremities (the upper part of the legs). In cats, the
distal extremities (the lower part of the legs) are
reported to be involved as often as the proximal
extremities. Katy’s x-rays were closely evaluated, and
were normal. In order to confirm her diagnosis, we
would have to do a more invasive procedure – a bone
marrow aspirate.
Multiple myeloma is a
cancer of the bone marrow. As such, evaluation of the
bone marrow would be expected to reveal the presence of
cancerous plasma cells. Analysis of the urine for Bence-Jones
proteins, and radiographs to look for the presence of
bone lysis are usually recommended first, as these are
non-invasive procedures and don’t require anesthesia.
In Katie’s case, these tests were negative. Katy was
anesthetized and a bone marrow aspirate and analysis was
performed. The results confirmed the presence of many
cancerous plasma cells in her bone marrow. My
suspicions were confirmed.
Treatment
In general, multiple
myeloma has been associated with long-term survival when
treated with chemotherapy. “The treatment that we use
for dogs also seems to be the most effective in cats,”
says Dr. Sue Cotter, an oncologist at the Cummings
School of Veterinary Medicine at Tufts University.
Prednisone (a glucocorticoid) and melphalan (an
alkylating agent), when used in combination, is an
effective regimen. “Other drugs might have some efficacy
if that combination is not effective” says Dr. Cotter.
I started Katy on
prednisolone and melphalan, and she joined Fred and
Sophie as the third member of my trio of recently
diagnosed multiple myeloma cases. I hope that Katy will
do as well as Bob, a handsome devil of a cat belonging
to Doug and Melanie West. Bob has been receiving
prednisone and melphalan for several months, and his
multiple myeloma is in complete remission.
Survival time for cats
with multiple myeloma is surprisingly good. For cats
that respond to chemotherapy, survival times can be as
long as 18 to 24 months, or even longer. As with all
cancers, early diagnosis and treatment is of paramount
importance if complete remission is to be achieved.
Sidebar: Common signs of multiple
myeloma in cats
·
Decreased appetite
·
Excessive thirst
·
Excessive urination
·
Weight loss
·
Bone pain
·
Bleeding/hemorrhage
Updated
05/10 |
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