LYMPHOCYTIC LEUKEMIA IN DOGS
Most of us have heard of leukemia and know it is a kind of cancer that people commonly get. We know it is generally a serious and often 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). This is actually a human sample.
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 needed 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.
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, 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).
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)
Pets with ALL are generally very sick and require aggressive chemotherapy. Often they need blood transfusions because of the severe anemia or antibiotics 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. Prognosis is poor when ALL is diagnosed so it is important to distinguish ALL from lymphoma or from more treatable forms of leukemia.
Because CLL progresses very slowly, treatment is often forgone unless one of several conditions are exist. Conditions for which treatment of CLL is recommended include: lymphocyte counts are greater than 60,000, if there are symptoms or organ enlargement, the presence of hyperviscosity syndrome (more common with B-CLL -see below) or if other white blood cell lines are suppressed by the tumor. If treatment is deemed necessary, common protocols involve prednisone, chlorambucil, vincristine and/or cyclophosphamide. Survival times of 1-3 years with good life quality are common.
WHAT ELSE COULD IT BE?
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:
WHAT IS A MONOCLONAL GAMMOPATHY? WHAT IS HYPERVISCOSITY SYNDROME?
Antibodies are members of a group of blood proteins called “gamma globulins.” When an infection occurs, B-cell lymphocytes begin to produce antibodies. Not all B-cell lymphocytes produce antibodies, only the ones that recognize the infectious organism. Each activated lymphocyte will divide over and over with all the daughter cells ultimately producing antibodies against a specific portion of the infectious agent. Each member of a line of daughter cells is called a "clone" and, when all is said and done, there are many clonal lines each producing their own unique antibody. The gamma globulin levels in the bloodstream are high because of all the antibodies present but because many clonal lines are involved, there are many antibody shapes present. This type of gamma globulin elevation is called a "polyclonal gammopathy" and generally indicates immune stimulation or infection.
Lymphocyte cancer is not like infection. Infection stimulates many lymphocyte clones to divide but cancer stems from one single cell gone wrong. There is only clonal line involved. If that clonal line is an antibody-producing lymphocyte line, then only one antibody is produced. The gamma globulin levels still rise but there is only one antibody shape present. This is called a "monoclonal gammopathy" because only one single line of daughter cells participates. This is a very unusual way for antibodies to be produced and the list of conditions that can stimulate only one clonal line like this is short:
The reason why monoclonal gammopathy 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.
It may be a good idea to consult with a specialist if your dog is diagnosed with leukemia as new treatments and funded clinical trials are at the heart of specialty practice.
TO LOCATE A VETERINARY ONCOLOGIST
Page last updated: 10/15/2021