Lymphoma in Dogs

Ouick Facts at a Glance

• Lymphoma and lymphosarcoma (LSA) are interchangeable terms
• Lymphoma in dogs is similar to non-Hodgkin's lymphoma in a man
• Lymphoma represents 7% of all cancers in dogs affecting 24/100,000 dogs at risk each year
• Most affected dogs are between 5-9 years of age, but the disease can occur in dogs of any age
• Generalized lymphadenopathy (lymph node enlargement) in an otherwise healthy dog is the most common presentation
• Hypercalcemia occurs in 20% of dogs with lymphoma
• Administration of glucocorticoids (steroids) prior to confirming a diagnosis can make obtaining the diagnosis more challenging

What are the clinical signs?

Generalized lymph node enlargement in an otherwise healthy dog is the most common presentation of LSA. This lymphadenopathy is non-painful and generally asymptomatic. This clinical presentation is referred to as stage IIIa LSA. Clinical signs will vary depending on the stage of disease, volume of tumor and anatomic location of the lymphoma. Clinical signs are typically non-specific and may include lethargy, weight loss and loss of appetite. If the patient has associated hypercalcemia, clinical signs will include polydipsia and polyuria (frequent drinking and urination). Other symptoms reflect the anatomic location of the lymphoma. Lymphoma of the gastrointestinal system generally results in vomiting and/or diarrhea whereas cranial mediastinal lymphoma results in dyspnea (difficulty breathing).

What should the work-up include?

A thorough physical examination is the most important part of the work-up. This dictates what diagnostic tests will be required to confirm the diagnosis and accurately determine the patient's health status. The diagnostic work-up should always include a complete blood count (CBC), platelet count, biochemical profile, urinalysis and fine needle aspirate or excisional biopsy of the lymph node. These tests allow us to confirm the diagnosis, determine if the patient is hypercalcemic, assess kidney function, and determine if the patient has normal neutrophil and platelet counts so that we can safely initiate chemotherapy.

A lymph node is excised for histopathologic analysis when the diagnosis cannot be confirmed by cytology. Lymph node biopsy has the added advantage of histologically classifying the LSA, which provides some additional prognostic information.

Alternatively, a DNA (gene) analysis test called PCR performed from a lymph node aspirate can be helpful to confirm a diagnosis in most cases.

When collecting a fine needle aspirate of the lymph node for cytologic evaluation, it is optimal to stay as far away from submandibular lymph nodes as possible. The increased reactivity of submandibular lymph nodes can sometimes mask neoplastic infiltrates. These lymph nodes should be only be used if other lymph nodes are not sufficiently enlarged or less accessible.

Additional diagnostic tests are required when complete staging of the lymphoma is desirable or when the patient is symptomatic. These tests may inclued chest and abdominal radiographs, abdominal ultrasound and ultrasound guided aspirates of the liver and spleen for cytologic evaluation, and bone marrow aspirate.

Is supportive care required before starting chemotherapy?

Most dogs with LSA are in good condition at the time of diagnosis and do not have any hematological or biochemical abnormalities. These dogs do not require supportive care. Once the diagnosis has been confirmed, chemotherapy can be initiated.

Hypercalcemia is the most common biochemical abnormality. If left untreated, hypercalcemia can result in severe or irreversible kidney failure. The kidney compromise, rather than the LSA, can become the life-limiting factor. The most important treatment of hypercalcemia is identifying and treating the underlying LSA. When the diagnosis of LSA cannot be readily confirmed, the patient should be treated with fluid therapy to maintain renal blood flow. T he fluid therapy of choice is 0.9% NaCl without additives. Depending on the state of hydration, fluid therapy should be administered at 1.5-2x maintenance level (45-60 mls/lb/24hours). Once fluid therapy has been initiated, furosemide (lasix) can be administered (1 mg/lb every 8-12 hours) to accelerate calciuresis. Although furosemide ultimately increases renal blood flow, it initially decreases renal blood flow and therefore should be avoided until the patient is re-hydrated. Prednisone and other glucocorticoids are very effective at reducing the blood calcium level but should be avoided until the diagnosis of LSA has been confirmed as they may alter the morphology of the tumor cells and make confirmation of a diagnosis quite challenging. Prednisone will not affect PCR results.

Hematologic abnormalities can occur if the bone marrow is infiltrated with lymphoma cells. The malignant lymphocytes will crowd the normal precursor cells in the bone marrow, preventing them from producing healthy neutrophils (white blood cells) and platelets (clotting factors). Consequently, neutropenia (low white blood cell count) and thrombocytopenia (low platelet count) develop. If severe, these hematologic abnormalitites can lead to bleeding and development of infections. The presence of neutropenia and thrombocytopenia will also affect our choice of chemotherapy drugs. Prednisone and vincristine can safely be given in these cases.

What is the prognosis for a dog with lymphoma?

Most dogs with lymphoma develop medium to high-grade lymphoma that is very responsive to chemotherapy. Greater than 75% of dogs with lymphoma are expected to achieve a complete remission with chemotherapy. The duration of the first remission is variable, depending on the chemotherapy protocol used, with median remission times varying from 6 months to 11 months. The second remission is more difficult to achieve, with approximately 40% of dogs with lymphoma achieving complete remission with a second course of chemotherapy. Less than 20% of dogs with lymphoma will achieve a third complete remission. Approximately 40-45% of dogs with lymphoma live one year with treatment. Less than 20% of dogs with lymphoma live 2 years with treatment. Without treatment, the average survival time of dogs is one month from the time of diagnosis. This is difficult for many pet owners to believe because their dog often appears to be quite healthy at the time of diagnosis.

How well do dogs tolerate chemotherapy?

Fortunately, most dogs tolerate chemotherapy extremely well. At our hospital, 75-80% of pet owners report that their pets' quality of life is acceptable to excellent while on treatment. However, 5-10% of dogs will have life threatening side effects, generally dehydration from vomiting and diarrhea. These patients require hospitalization and appropriate therapy to recover from the toxicity. Chemotherapy is generally discontinued in these patients once they have recovered from the toxicity. Because lymphoma is not a curable cancer, it is critical that the patient's quality of life is good the vast majority of time. Acceptable side effects may include short-term (1-2 days) loss of appetite, vomiting, diarrhea and listlessness. The patient should quickly bounce back to normal. Some patients will require a dose adjustment after their first chemotherapy treatment or require anti-nausea or anti-diarrhea medication to reduce the duration of side effects.

Why do we treat dogs with lymphoma?

Pets are an important part of our lives and our families. The decision to treat lymphoma is not always clear-cut. There are emotional and financial considerations. The objective of treatment is to extend the pet's life with good quality time. If we are able to achieve complete remission of the lymphoma and the quality of the pet's life is good, the extra time is enjoyed both by the pet and the pet owner.

What are the treatment options?

Multi-drug protocol : Treatment consists of the use of several chemotherapy drugs (prednisone, L-asparaginase [elspar], vincristine, cyclophosphamide [cytoxan] and doxorubicin [adriamycin]). Weekly chemotherapy treatments are given for approximately 8 weeks. The treatments are then spaced to every 2 weeks to complete a total of 6 months of treatment. The average survival time for patients with stage IIIa or IVa lymphoma treated with this protocol is 1 and 1/2 years.

Doxorubicin alone : The patient is treated with a total of 5 treatments of doxorubicin at 3-week intervals. The average survival time with this approach is 10-11 months.

COP: This protocol involves a combination of cyclophosphamide in tablet form, vincristine and prednisone. 4 weekly intravenous injections of vincristine are given, followed by injections at 3-week intervals to complete 6 months of treatment. Cyclophosphamide is given over 4 days every 3 weeks (4 days on; 17 days off). Prednisone is given daily for 6 months. The average survival time with this protocol is reported as 8-10 months.

Prednisone alone : This medication is a steroid and can be given in pill form daily at home. The average survival time for patients with lymphoma treated with prednisone only is 60 days.

Comments : numerous chemotherapy drugs are available. These drugs may be used along with the above mentioned chemotherapy drugs. The protocols listed above are currently the best options available for treatment of a first remission.

Table: Clinical staging of lymphoma