In dogs, lymphoma primarily affects lymphoid tissues of the bone marrow, thymus, lymph nodes, and spleen, but other organs can be affected, including skin, eye, kidneys, brain, testis, prostate and bone.
The cause(s) of malignant clonal expansion of lymphoid cells associated with lymphoma remains poorly understood. Some hypotheses have been forwarded, including:
- Genetic susceptibility
- Toxins - including lawn care pesticides (phenoxy herbicides), magnetic field exposure, chromosomal abnormalities (Monosomy X mutagenesis)
- Dietary preservatives
- Viral diseases
- Concurrent parasitism
The traditional classification of lymphomas as Hodgkin or non-Hodgkin lymphomas has recently been abandoned for more generalized nomenclature involving listing of individual types of lymphoma instead, including:
- Multicentric B-cell or T-cell lymphoma - may result in secondary leukemia
- Alimentary lymphoma (from oral to rectal lymphoma), including intestinal polyposis
- Mediastinal lymphoma
- Extranodal lymphoma
- - Renal lymphoma
- - Pulmonary lymphoma
- - Hepatosplenic and Hepatocytotropic T-Cell Lymphoma
- - Primary CNS lymphoma
- - Epitheliotropic T-cell lymphoma
- - Ocular and adnexal ocular lymphoma (e.g. uveodermatologic lymphoma)
- - Waldenström's macroglobulinemia (lymphoplasmacytic lymphoma)
- - Mucosa-associated lymphoid tissue lymphoma - MALT lymphoma
- - Prostatic lymphoma
- - Polyostotic lymphoma
- - Intravascular lymphoma
- - Neurolymphomatosis - invasion of regional nerves - often presents as local paralysis and metastases
- - Indolent nodular lymphoma
B-cell lymphomas, the less life-threatening of the two forms, have a clear hierarchy of progenitor cells responsible for initiation of neoplasia in dogs as well as high telomerase activity (which confers cell immortality) and resistance to adenovirus uptake, making in vivo gene delivery using capsid-modified vectors difficult to trial as chemotherapeutic agents.
Affected dogs usually show early vague clinical symptoms such as vomiting, diarrhea, protein-losing enteropathy, dyspnea (due to pleural effusion, chylothorax or pyothorax), weight loss and in some cases palpable lymphadenopathy. In intracranial lymphoma, seizures are common.
Multicentric lymphoma is by far the most common form, accounting for ~80% of all diagnosed cases, followed by mediastinal and alimentary lymphoma. A significant proportion are indolent lymphomas (slow, insidiously developing).
Diagnosis of lymphoma is usually determined by biopsy obtained by fine needle aspirate or laparotomy. Other clinical symptoms may assist, such as lymphadenopathy in the case of multicentric lymphoma.
Insidious lymphomas may be difficult to confirm without ancillary tests (e.g. ultrasonographic or radiographic studies) as historical evidence is often vague. Ultrasonography affords high predictive value for hepatic and splenic lymphomas.
Laparotomy is usually conducted to visualize visceral lymphomas.
Primary or secondary cerebral lymphomas usually require CT or MRI imaging to accurately assess morphology.
Many types of B-cell lymphomas are now readily assayed with PCR tests, amplifying the rearranged immunoglobulin heavy chain gene of neoplastic B-cells. These tests can be used both as diagnostic tests as well as assessing chemotherapeutic effects.
Lymphomas are often stage histologically:
- - Stage I: one lymph node affected
- - Stage II: two lymph nodes (on the same side of the diaphragm) affected
- - Stage III: multiple lymph nodes affected
- - Stage IV: the liver and spleen are affected
- - Stage V: the bone marrow is affected (lymphoma and leukemia)
Variations exists between pathologist's interpretations and staging is primarily a predictor of response to therapy. Regardless of staging or classification, the overall response rate of dogs with B-cell lymphoma approaches 100% when using drugs such as doxorubicin, compared with a response rate of 50% in dogs with T-cell lymphoma.
Regardless of the classification of lymphoma, most veterinary treatment revolves around palliative care and a choice of one or more chemotherapeutic drugs. Palliative care cannot be over-emphasized, particularly in young or geriatric patients.
Predictors of long-term survival in dogs with high-grade multicentric lymphoma include a body weight ≥ 10 kg, a PCV ≥ 35%, absence of ionized hypercalcemia, monocyte chemotactic protein-1, centroblastic lymphoma, immunophenotype B, absence of bone marrow involvement, and not previously treated with corticosteroids.
A number of protocols are available, depending on the client's needs and the veterinarian's skills. Generally speaking, dogs treated with multi-agent chemotherapy protocols have longer survival times.
Treatment can be based on Kamofsky's performance criteria, which uses criteria of well-being as a determinant for assessing suitability of canine patients to chemotherapy regimens.
Types of treatments for lymphoma include:
- Surgical debulking of single solid tumors if restricting vital organs
- Multi-drug protocol - use of several chemotherapy drugs (prednisolone, L-asparaginase, vincristine, cyclophosphamide, doxorubicin, idarubicin and epirubicin). 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.
- Madison Wisconsin lymphoma protocol
- MOPP lymphoma protocol
- University of Florida protocol - lomustine, vincristine, procarbazine and prednisolone
- University of California CHOP protocol - cyclophosphamide, doxorubicin, vincristine and prednisone. Average survival time 8 - 10 months
- University of Winsconsin 19 week CHOP protocol - cyclophosphamide, doxorubicin, vincristine and prednisolone. Risk of neutropenia and gastrointestinal toxicoses
- COAP protocol - cyclophosphamide, vincristine, cytarabine and prednisolone
- DMAC protocol - dexamethasone, melphalan, actinomycin D and cytarabine - effective rescue protocol for dogs with relapsed multicentric lymphoma
- Single drug protocol
- - Doxorubicin - a total of 5 treatments of doxorubicin at 3-week intervals. The average survival time with this approach is 10-11 months.
- - Dacarbazine - single-agent therapy for relapsed lymphoma
- - Prednisolone - often used as a palliative drug in non-compliant patients or financially challenged cases. Survival time limited to 2 - 3 months.
- - Lansoprazole - rescue protocol in dogs in dogs with adverse side-effects associated with chemotherapy
- Total body irradiation or myeloablative chemotherapy (e.g. busulfan) followed by 7 day course of colony stimulating factor then autologous bone marrow transplantation
- Immunotherapy with multivalent immunogens
Without treatment, most dogs will die within 1 - 2 months from organ failure. For Stage III lymphoma, 80 - 90% of dogs undergo clinical remission (absence of clinical or ultrasonogrpahic evidence of neoplasia). Stage IV lymphomas have a cure rate of 60 - 80% and Stage V about 50%. If a dog does go into remission, then a first remission of 9 - 14 months is most common. Second remissions can be obtained, but they are harder to obtain and do not last as long as the first.
In most cases of lymphoma, the dose of chemotherapy cocktails (e.g. COP protocol) does not necessarily correlate with patient outcomes and must be re-evaluated in light of quality of life factors.
Many forms of lymphoma cases achieve complete clinical remission following chemotherapy, but relapse due to drug resistance.
In dogs with B-cell lymphoma, response to therapy can be predicted based Class II MHC expression, cell size, chemotherapy treatment and age. B-cell lymphoma, which, if treated with multi-agent chemotherapy, has a survival time of approximately 12 months.
Failure of response to primary or secondary course of chemotherapy must be weighed up against quality of life, which must be the priority for continuing further treatment.
In cases which are already advanced at the time of diagnosis due to neglect or financially-constrained owners, palliative care followed by euthanasia a few weeks or months later may be an only option.
- Tufts University
- Veterinary Dentistry
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