Canine Lymphoma:
Over the past years, the animal-owner relationship has been changing and pets have genuinely become part of the human family. Concomitantly, advances in veterinary care have emerged resulting in an increased life expectancy of dogs.
Since dogs live in close proximity to humans, they are influenced by similar environmental factors that may lead to chronic diseases and cancers. Consequently, malignant diseases, mainly canine lymphoma, are becoming the main causes of deaths in dogs worldwide.
But what exactly is canine lymphoma? And how is it treated?
Vet. Sci. 2016, 3, 7; doi:10.3390/vetsci3010007
Because lymphoma commonly develops in companion animals, veterinary practitioners should be knowledgeable about the treatment options available. Therefore, the focus of this review article is to highlight some of the more conventional therapeutic modalities useful for treating high-grade lymphoma in dogs.
Canine Lymphoma:
The malignant transformation of any lymphocyte population, termed lymphoma, is the most common blood cancer observed in dogs. This hematopoetic malignancy affects the immune system, specifically lymphocytes and lymphoid tissues (present in many places in the body, including the lymph nodes, spleen, gastrointestinal tract and bone marrow). It afflicts middle-aged to older dogs, but dogs of any age are at risk. Certain breeds are predisposed to this malignancy including Boxers, German Shepherds and Golden Retrievers, yet the cause of its occurrence is still unknown.
There is no apparent sex predisposition, but intact female dogs appear to have a reduced risk and early (<1 year) neutralization has been suggested to increase the risk of developing canine lymphoma in the golden retriever but not in the Labrador retriever.
Zandvliet, M. "Canine lymphoma: a review." Veterinary Quarterly 36.2 (2016): 76-104.
Since it starts in the lymph nodes, it’s not considered a singular cancer; rather, divergent categories of lymphoma behave differently and require specific therapies.
Lymphoma can affect many different areas of the body, and in dogs, four recognized anatomic forms of lymphoma exist and include:
- Multicentric (Affects the peripheral lymph nodes)
- Alimentary (Affects the gastrointestinal (GI) tract)
- Mediastinal (Affects the organs within the chest, such as lymph nodes or the thymus gland)
- Extranodal (Affects organs outside the lymphatic system)
Multicentric lymphoma is the most common form encountered in dogs. Affected subjects present a non-painful, generalized, peripheral lymphadenopathy, and malignant lymphocytes may infiltrate into other organs including the spleen, liver, bone marrow, and other extranodal sites. Whereas others exhibit more marked clinical signs, including lethargy, anorexia, polyuria and polydipsia and in many cases, the only noticeable sign of disease is enlargement of the lymph nodes under the neck, in front of the shoulders, and/or behind the knees.
Alimentary lymphoma may develop at any area of digestive tract, including the stomach, small intestine, large intestine and/or rectum. Dogs with alimentary lymphoma may manifest with significant gastrointestinal signs, including anorexia, vomiting, diarrhea, and profound weight loss secondary to severe malabsorption and maldigestion of nutrients due to loss of appetite.
Mediastinal lymphoma is characterized by the enlargement of the cranial mediastinal lymph nodes and/or thymus. Because the thymus serves as the central lymphoid organ for maturing T lymphocytes, many mediastinal lymphomas are exclusively of Tcell origin. It is more common in younger dogs that might suffer from respiratory complications caused by pleural fluid accumulation and pleural effusion due to obstruction of lymphatic return.
In addition to that, other clinical signs include polyuria/polydipsia (due to hypercalcemia), and an important syndrome may arise, the so-called vena cava syndrome, characterized by a restriction of the venous return caused by the mediastinal mass.
Extranodal lymphoma Targets a specific organ, such as the skin, eyes, kidneys, lungs, or central nervous system, the most common one affecting the skin (cutaneous lymphoma). Clinical findings can be quite variable; giving the example of cutaneous lymphoma, it can manifest with a wide spectrum of clinical presentations ranging from solitary, raised, ulcerative nodules to generalized, diffuse, scaly lesions.
How is Canine Lymphoma Treated?
Three major types of treatments underlie all cancer therapy: surgery, radiation therapy and chemotherapy. Since lymphoma is widespread throughout the body at the time of diagnosis, surgery is not generally used for treatment as removal of all the lymph tissue in the body is impossible. Although radiation therapy can be used in select cases of canine lymphoma, chemotherapy remains the best option for treating canine lymphoma.
Standard chemotherapeutic treatment options:
Canine lymphoma exhibits a positive response to treatment with chemotherapy by providing many dogs with prolonged survival times and high quality of life scores.
Most traditional chemotherapy protocols have 2 phases: induction and consolidation. The induction phase consists of weekly treatments designed to place the dog into remission rapidly. It is more dose intensive than the consolidation phase, which is designed to kill any remaining tumor cells and requires less frequent treatment.
During the induction phase, dose-intense cytotoxic chemotherapy is administered at frequent intervals over a relatively short time frame, killing most viable cancer cells. After induction chemotherapy, lower dose intensity, long-term chemotherapy called maintenance/consolidation therapy is instituted to prevent or delay microscopic tumor regrowth.
Maintenance therapy necessitates long-term follow up treatment which might be draining for the patient and the pet owner. Moreover, new studies show that administering chemotherapy over a prolonged period result in cumulative and irreversible bone marrow toxicity.
Fan, Timothy M., and Louis Philippe De Lorimier. "Treating lymphoma in dogs and cats." Veterinary medicine 100.4 (2005): 285-294.
In the past few years, new shorter chemotherapeutic treatment protocols have excluded the use of maintenance chemotherapy, while retaining high therapeutic efficacy. But, although these protocols provide durable first remission times, dogs suffering from lymphoma should be routinely monitored and evaluated by a veterinarian at least three or four times a year since most dogs with lymphoma are not cured of their disease, but the risk of lymphoma relapses diminishes if a proper follow up through routine health screening is performed.
There are numerous chemotherapy treatment protocols for dogs with multicentric lymphoma, combination chemotherapy for canine lymphoma incorporates 5 active drugs (prednisone, L-asparaginase, vincristine, doxorubicin and cyclophosphamide).
For instance, dogs with multicentric lymphoma are often given the chemotherapy protocol UW-25, which is based on the CHOP protocol used in humans
What is CHOP protocol?
CHOP is a multi-agent chemotherapy protocol that uses 4 different drugs—Cyclophosphamide, Doxorubicin Hydrochloride (sometimes called Hydroxydaunomycin), Vincristine sulfate, and Prednison
- C (Cyclophosphamide):Cyclophosphamide is a type of nitrogen mustard drug which exerts its effects through the alkylation of DNA. Once metabolized to its active form, this drug inhibits protein synthesis through DNA and RNA crosslinking, resulting in the inhibition of cancer cell growth. It can be given intravenously or in capsule form.
- H (Doxorubicin):This antineoplastic anthracycline class affects different mechanisms of actions, including: - Enzyme interaction (topoisomerase-II) causing growth arrest and apoptotic cell death.
- DNA intercalation inhibiting DNA and RNA synthesis, especially in highly replicating cells blocking cell division.
- O (Vincristine): Its mechanism of action has been related to the inhibition of microtubule formation in mitotic spindle, resulting in an arrest of dividing cells at the metaphase stage. Vincristine is a vesicant and must be administered with care by a trained technician through a perfectly placed butterfly or over-the-needle catheter.
- P (Prednisone):This corticosteroid is immunosuppressive if administered in high doses, affecting the proliferation of malignant cells and accelerate their apoptosis.
Although it is proven that chemotherapy can be highly effective for treating lymphoma and can increase a dog’s life expectancy, the veterinary industry is yet to determine the best treatment option with minimal side effects and optimal results. Therefore, it is essential to work closely with a veterinarian to determine the best treatment plan for the dog, including monitoring their response to treatment and adjusting it as needed.