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Canine Leukemia
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THE PET HEALTH
LIBRARY
By Wendy C. Brooks, DVM, DipABVP
Educational Director, VeterinaryPartner.com
Lymphocytic Leukemia in
Dogs
Most of us have heard of leukemia
and know it is some kind of cancer that people commonly get. We know it
is generally a very serious and commonly fatal disease. This article explains
what leukemia is, why it is bad, and reviews the most common forms of leukemia
for dogs: the lymphocytic forms.
Leukemia is a word describing exactly what it is: “Leuk” means white
(in this case white blood cells) and “emia” means blood. Leukemia literally
means “white blood” or more specifically an over-abundance of white blood
cells in the bloodstream. Now, white blood cell counts elevate in response
to infection, inflammation, allergy, and even stress. We are not talking
about elevations in these ranges. The patient with leukemia has an over-abundance
of a particular white blood cell but in magnitudes so great that it is
amazing that the change cannot be seen with the naked eye. The bloodstream
is swarmed with cancerous white blood cells and the bone marrow from whence
they came is consumed with making cancer cells and making very few of the
other blood cells we need to survive. In the case of lymphocytic leukemia,
the cancer cells are of lymphocyte origin, though there are many other types
of leukemia, potentially one for every type of blood cell made by the bone
marrow. In this article, we'll stick to the lymphocytic leukemias.
What Causes Lymphocytic Leukemia?
In dogs, we do not have much of a list of possibilities though in other
species some culprits have been identified. It may be that these same factors
are causes in dogs as well. In humans, radiation exposure had been linked
to lymphocytic leukemia development as has exposure to benzene. In cats,
bird, and cattle there is a “leukemia virus” (though not the same virus for
these different animals). Not surprisingly, given the name, leukemia viruses
cause leukemia, as well as other lymphocytic cancers such as lymphoma.
Chronic Versus Acute Lymphocytic Leukemia
In most of these patients, the diagnosis of lymphocytic leukemia is clear
when an impossibly high lymphocyte count is seen. (A normal lymphocyte
count is generally less than 3,500 cells per microliter. In lymphocytic
leukemias, lymphocyte counts over 100,000 are common.)
Numbers of this magnitude generally flag the sample at the reference
laboratory for reading by a clinical pathologist (or if the initial testing
is done in the veterinarian’s office, the lymphocyte reading will cause
the sample to be submitted for further analysis). The pathologist will then
review the slide visually for signs of malignancy within the cells. The
diagnosis of lymphocytic leukemia is usually fairly obvious (for exceptions
see below) but the key is to determine whether the lymphocytic leukemia
is chronic or acute.
Normally the term “chronic” means a process or disease has been going
on for a long time and “acute” means that the process started suddenly. For
lymphocytic leukemia, these terms have a different meaning: they refer to
how mature the cancer cells look. Lymphocytes develop from precursor cells
in the bone marrow or lymph nodes and undergo several stages of development
before they are released into the bloodstream. When a leukemia involves
earlier stages of lymphocytes, it is said to be an acute leukemia. When
cells are more developed, the patient is said to have a chronic leukemia.
As a general rule, the acute leukemias act more malignantly than the chronic
ones. There is some controversy over whether acute or chronic lymphocytic
leukemia is more common.
Acute Lymphocytic Leukemia (ALL)
The bottom line here is that ALL is a very bad disease. Cancer starts
in the bone marrow and quickly spreads to the bloodstream, spleen and liver.
The bone marrow is nearly obliterated by the cancer cells, leading to deficiencies
in the other blood cells the bone marrow is supposed to be making. The
circulating number of lymphocytes is generally extremely high though in
early stages possibly low enough to make the diagnosis equivocal. The most
common symptoms include: listlessness, poor appetite, nausea, diarrhea,
and weight loss. The average age at diagnosis is only 6.2 years with 27%
of patients being under age 4 years. Over 70% of patients have enlarged spleens
due to cancer infiltration, over 50% have enlarged livers, and 40% to 50%
have lymph node enlargement (though this is not dramatic). On lab tests,
over 50% will have anemia (red blood cell deficiency), 30% to 50% will have
a platelet deficiency (platelets are blood clotting cells so deficiency can
lead to spontaneous bleeding), and 65% have what is called neutropenia. Neutrophils
are white blood cells that serve as the immune system’s first line of defense.
Neutropenia is a neutrophil deficiency that leaves the patient vulnerable
to infection.
Dogs with ALL are generally very sick and require aggressive chemotherapy.
Often they need blood transfusions because of the severe anemia or antibiotic
to make up for the neutropenia. Typical chemotherapy protocols include:
prednisone, vincristine, cyclophosphamide, L-asparaginase and doxorubicin.
Still, even with aggressive chemotherapy only 30% of patients achieve remission
and with no therapy most patients die within a few weeks.
Chronic Lymphocytic Leukemia (CLL)
As rapid and aggressive as acute lymphocytic leukemia is, chronic lymphocytic
leukemia is the opposite. The clinical course is long (months to years)
with the average age at diagnosis being 10 to 12 years. In up to 50% of
cases, there are no symptoms of any kind at the time of diagnosis and the
leukemia is discovered on a routine blood evaluation. Neutropenia is a rare
complication of CLL, though 80% have anemia, 70% have enlarged spleens,
and 40% to 50% have liver enlargement.
The course of this disease is very slow with patients living 1 to 2 years
even without chemotherapy. Signs that chemotherapy are needed include lymphocyte
counts greater than 60,000, anemia, low platelets, or risk for a complication
called “hyperviscosity syndrome.” (see below). Common protocols involve
prednisone, chlorambucil, and cyclophosphamide.
What Else Could It Be?
In most cases, the diagnosis is fairly obvious but not always. In early
cases, the lymphocyte count may not have climbed to its ultimate level so
the diagnosis may be unclear. Similarly, in very late stages the bone marrow
may be so damaged that it can no longer turn out many cells at all. In these
cases, special tests may be needed because when lymphocytic leukemia is ambiguous,
there are other diseases that must be ruled out:
Lymphoma in its most advanced stages involves the bone marrow and circulating
cancerous lymphocytes spill into the bloodstream. (Dramatically enlarged
lymph nodes, if present, are a good indicator of lymphoma; lymphocytic leukemia
patients usually have mild or no lymph node enlargement).
Infection with the blood parasite Ehrlichia canis can lead to very high
lymphocyte counts and can be very hard to distinguish from CLL. Special blood
tests for Ehrlichia may be in order.
Some other types of leukemia can be so poorly differentiated that special
stains, PCR testing or a special type of analysis called immunophenotyping
might be necessary to characterize the type of cancerous white blood cells
involved.
Acute stress can cause lymphocyte counts as high as 15,000 cells per
microliter but this is a very temporary phenomenon.
Hypoadrenocorticism (“Addison’s Disease”) can lead to a lymphocyte count
up to 10,000 cells per microliter.
Chronic infection with fungus (if severe) or blood parasites can elevate
lymphocyte counts dramatically.
Lymphocyte counts over 20,000 are almost always from a lymphocytic leukemia.
What Is a Monoclonal Gammopathy? What Is Hyperviscosity Syndrome?
There are several conditions that can cause a complication called a monoclonal
gammopathy. We all know that antibodies are produced in response to infection.
Antibodies are members of a group of blood proteins called gamma globulins.
When antibodies are produced in response to infection, many different types
of antibodies are produced that would create a “polyclonal” gammopathy.
A “monoclonal” gammopathy is an elevated gamma globulin level due to very
high levels of one particular type of antibody. This is a very unusual way
for antibodies to be produced and the list of conditions that can produce
it is short:
Ehrlichia infection (the only non-tumorous cause)
Lymphoma
Plasma cell cancer (“multiple myeloma”)
B cell chronic lymphocytic leukemia
The reason why this particular potential complication of CLL is bad is
because it can cause “hyperviscosity syndrome.” Antibodies are blood proteins
and if one circulates enough blood protein, the blood actually thickens.
Smaller blood vessels are too delicate to circulate thickened blood. They
break and bleeding results. What symptoms occur depend on where these small
vessels bleed. There could be nose-bleeding, seizures, blurred vision or
even blindness.
In one study, monoclonal gammopathy was very common in dogs with CLL.
Antibodies, also called immunoglobulins, are classified as different types:
IgG, IgA, IgE, IgM, and IgD. Monoclonal gammopathy from CLL is almost always
of the IgM type, while monoclonal gammopathy from Ehrlichia infection produces
IgG antibodies.
If your dog has been diagnosed with a lymphocytic leukemia, you may want
to be referred to an oncologist for the most up to date recommendations.
Copyright
2007 - 2007 by the Veterinary Information Network, Inc. All rights reserved.
This work was originally published by Veterinary Information Network,
Inc. (VIN)
and is republished with VIN's permission.
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The above information is simply informational.
It's intent is not to replace the advice of a veterinarian nor to assist
you in making a diagnosis of your pet. Please consult with your own veterinarian
for confirmation of any diagnosis. Your pets life may depend on it.
