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 - 2009 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.
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.
