Most of us have heard the term “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 and why it is bad and reviews the most common forms of leukemia for dogs: the lymphocytic forms.
The large purple cells are circulating
malignant lymphocytes (leukemia cells)
(graphic courtesy of the University of Georgia)
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 will stick to the lymphocytic leukemias.
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, birds, 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).
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.
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 40-50% have lymph node enlargement (though this is not dramatic). On lab tests, over 50% will have anemia (red blood cell deficiency), 30-50% 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 which 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-asparginase and doxorubicin. Still, even with aggressive chemotherapy only 30% of patients achieve remission and with no therapy most patients die within a few weeks.
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 10-12 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 40-50% have liver enlargement.
The course of this disease is very slow with patients living 1-2 years even without chemotherapy. Signs that chemotherapy are needed include lymphocyte counts > 60,000, anemia, low platelets, or risk for a complication called “hyperviscosity syndrome.” (see later). Common protocols involve prednisone, chlorambucil, and cyclophosphamide.
In most cases, the diagnosis is fairly obvious though this is not always the case. 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.
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 which 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)
- 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 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.
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Page last updated: 8/18/10