Lymphoma in dogs and cats (Proceedings)

Canine Lymphoma

Canine lymphoma comprises approximately 7-24% of all canine neoplasia and 83% of canine hematopoietic malignancies. This translates to ~24/100,000 dogs at risk and is one of the most commonly treated malignancies both in the private practice and specialty setting.

Lymphoma is a very diverse group of neoplasms whose etiology remains largely unknown. Viral particles similar to those of retroviruses have been identified in short term culture. Exposure to phenoxyacetic acid herbicides has been implicated in both human and canine patients, but account for a very small percentage of cases. Its incidence is noted to be increased in immunosuppressed patients. Chromosome abnormalities are being described more frequently, and serve as markers, and in some cases prognostic factors, for subtypes of several lymphomas in human medicine. These chromosome abnormalities are now starting to be identified in our canine patients as well.

Classification in dogs has long been based on anatomic location and histologic criteria. Anatomic forms include multicentric (80%), anterior mediastinal (~5%), gastrointestinal (~5-7%), cutaneous (~5%) and extranodal (~5%). The clinical signs associated with each reflect the organ system involved. Hypercalcemia is a common paraneoplastic syndrome noted in the anterior mediastinal form. Anemia, neutrophilia, lymphocytosis, thrombocytopenia, monoclonal gammopathies and cachexia have all been reported.

Histologically they are most often broken down into high, intermediate and low grades. The most striking difference between canine and human cases is the paucity of low-grade canine tumors (5.3-29%). The histologic classification does not predict survival times, but does predict the response to therapy. The high grade tumors are more likely to respond to chemotherapy, however the low grade tumors can live a long time without any treatment.

Lymphomas can also be B-cell or T-cell in origin. Approximately 85% of canine cases are B-cell in origin and historically they have been more responsive to treatment and associated with longer survival times. Chemotherapy protocols in the future will be based upon immunophenotype classification and this information should be requested routinely. The immunophenotype can be determined using cytologic or histologic samples, and is available through all of the commercial laboratories.

WHO clinical staging is broken down into five categories. I. Involvement limited to a single node or organ. II. Regional lymph node involvement on one side of the diaphragm. III. Generalized lymph node involvement on both sides of the diaphragm. IV. Liver and/or spleen involvement. V. Bone marrow and/or extranodal involvement. In addition each is further classified into a substage of a) without systemic signs and b) with systemic signs. Stage is not generally prognostic unless you are lucky enough to have a I or II. Substage however is highly prognostic with those animals without systemic signs generally living longer.

Baseline staging should always include a CBC, biochemical profile, urinalysis, and immunophenotyping. Thoracic and abdominal radiographs, bone marrow aspirates, and bronchoalveolar lavages can also be considered to thoroughly stage your patient. The more aggressively you stage them, the higher their classification will be. The treatment of these patients is going to be dictated by the stage and substage of the disease, the immunophenotype, the presence or absence of paraneoplastic signs, the overall physiologic status of the patient, the financial and time commitment of the owner, and the client's overall comfort with the potential side effects. Note that the last category is the only one you can impact.

Without treatment median survival times of 30-50 days are reported. Since with few exceptions, this is a systemic disease, systemic treatment is required, therefore chemotherapy is the treatment of choice. With the possible exception of doxorubicin, single agent therapy results in lower response rates and survival times. Approximately 90% of lymphoma patients can be placed into a complete clinical remission and a return to a normal quality of life. The median survival time is ~ 1 year in dogs treated aggressively and most dogs tolerate their chemotherapy with minimal side effects. The most effective chemotherapy agents include doxorubicin, cyclophosphamide, vincristine, l-asparaginase, CCNU and prednisone. Other drugs with activity include vinblastine, cytosine arabinoside, actinomycin-D, mitoxantrone, chlorambucil, mustargen, procarbazine and DTIC.

The standard of care has long been a CHOP multidrug protocol. The most commonly used protocol was developed at the University of Wisconsin and several modifications have been published. All versions entail the use of doxorubicin, vincristine, cyclophosphamide and prednisone. Modifications have included l-asparaginase, changing the intervals between treatments, or changing the initial drug given. All of them can be expected to place ~90% of patients into a complete remission for an average of 8-10 months. There is little doubt a CHOP protocol should be the most effective for a B-cell lymphoma patient.

When finances or time constraints limit the clients ability to pursue a multi-drug protocol, doxorubicin as a single agent will place the majority of B-cell lymphoma patients into a complete remission for 6-9 months. Other drugs can still be effectively used at the time of first relapse.

Recent evidence would indicate that T-cell tumors are not as responsive to doxorubicin, therefore a CHOP protocol may not be optimum for these cases. Most studies indicate that a CHOP protocol will work for an average of ~150 days in T-cell cases. MOPP has a very similar response duration. This author has recently been working with a combination of l-asparaginase, vincristine and CCNU as the latter seems to be the most effective single agent for our T-cell cases.

Long term control is achieved in at least half of human patients with bone marrow transplants and these may become more widely available to our canine patients in the near future.

In summary, the average lymphoma patient can be expected to enter a complete clinical remission 90% of the time with an average duration of one year. Positive prognostic factors include the B-cell immunophenotype, lack of systemic signs at presentation and no history of steroid administration.

Feline Lymphoma

This was once a disease of young, FeLV+ cats with anterior mediastinal disease. They account for a very small percentage of cases today. The typical patient now is 10 years old, is retrovirus negative and has the gastrointestinal form of the lymphoma. Both B- and T- cell tumors are noted, with the most recent studies indicating that T-cell tumors are most common.

Histologic grade is very important in the cat. The small cell, well-differentiated, low-grade lymphoma is going to do very well with a simple combination of oral chlorambucil and prednisone. High grade tumors must be treated more aggressively. A CHOP protocol is also considered by most to be the standard of care for high grade feline cases. It is not yet known whether the same differential in sensitivity to doxorubicin between B- and T-cell tumors exists in feline patients.

Overall complete remission rates in high grade lymphoma in the cat have been reported between 50-70% with median remission times of 6-8 months. Approximately 30-35% will live longer than one year. The poorest prognosis is associated with mediastinal and renal forms and/or a positive retroviral status.