Most forms of lymphoma are multicentric and therefore demand a systemic approach. This is why chemotherapy is the preferred treatment option for most forms of lymphoma, as chemotherapeutics reach cancer cells via the bloodstream. Chemotherapy is very well tolerated by companion animals. If the lymphoma is restricted to one location, local removal via surgery or radiotherapy is the preferred treatment option.
Combination chemotherapy is most frequently used for the treatment of a malignant form of lymphoma. Combination chemotherapy consists of different kinds of chemotherapeutics that are sequentially administered during the course of the treatment. The treatment duration and which chemotherapeutics are exactly used, depends on the (sub)stage of the lymphoma, the presence or absence of paraneoplastic disease, the general state of the dog, the balance between the dog’s wellbeing and treatment response, side effects of the treatment and of course the time and budget the owners can invest (some protocols take up to 24 weeks with weekly treatments, others 15 weeks with treatment every 3 weeks). Combination chemotherapy is generally preferred over chemotherapy with only one kind of cytostatic drug, as the effect is better and lasts longer.
Remission (the disappearance of the tumour) occurs in 80 to 90% of dogs after combination chemotherapy. The median survival time is 10 to 12 months. After 2 years, 20-25% of dogs treated with combination chemotherapy are still alive when treated for multicentric B cell lymphoma.
The cost of combination chemotherapy depends on the chemotherapeutic used, the size of the animal, the frequency of administration and (lab) monitoring. Before each chemotherapeutic treatment, a blood examination should be done to evaluate whether the levels of certain blood cells are sufficiently high. If the levels are too low, treatment should be withheld and the blood should be checked again after 3 to 7 days. If there’s lymphoma present in the bone marrow, the blood levels are more difficult to interpret.
Although the lymphoma will initially disappear in many dogs, most will relapse (generally within 1 year). This is generally due to the fact that in most cases not all tumour cells can be killed by chemotherapy, the number can only be decreased up to a certain point. After that it's up to the body's own immune system whether it is able to eliminate the residual tumour cells or not. A non-response or early relapse can be due to an initial treatment with prednisolone, administration of lower doses of cytostatic drugs (in line with the dog’s wellbeing), insufficiently high penetration of the chemotherapeutic drug into the tumour, or because the cancer cells became resistant to the chemotherapeutics. Although the lymphoma will initially disappear in many dogs, most will relapse (generally within 1 year). This is generally due to the fact that in most cases not all tumour cells can be killed by chemotherapy, the number can only be decreased up to a certain point. After that it's up to the body's own immune system whether it is able to eliminate the residual tumour cells or not. A non-response or early relapse can be due to an initial treatment with prednisolone, administration of lower doses of cytostatic drugs (in line with the dog’s wellbeing), insufficiently high penetration of the chemotherapeutic drug into the tumour, or because the cancer cells became resistant to the chemotherapeutics.
When a dog relapses, it’s necessary to repeat the treatment or to start up another treatment protocol with substances the dog has not received before (rescue protocol). In case of a high-grade form of lymphoma, a single chemotherapeutic drug will typically not lead to a durable remission compared to the standard combination protocols.
Of note, for certain types of low-grade lymphoma, the use of metronomic oral cytostatic drugs with low levels of side effects - possibly combined with prednisolone- can lead to a long survival time. These subtypes are called “indolent lymphoma”. They make up about 5-10% of all lymphomas.
Enzyme therapy such as PEG asparaginase (Oncaspar®) offers an alternative to those who do not want to start with chemotherapy for the treatment of malignant lymphoma forms or leukaemia. It is also used in conjunction with chemotherapy. This enzyme breaks down nutrients (the amino acid asparagine) for the cancer cell, preventing it from multiplying.
This therapy does not achieve a cure, but rather suppresses the disease. The drug is quite safe for the dog and the waste products from PEG asparaginase are less harmful than those from chemotherapy. As a result, owners do not have to take precautions with faeces / urine / saliva. This option is often recommended (as opposed to chemotherapy) when pets are part of a family with children or live with pregnant women. There is no need for intravenous administration and bone marrow suppression rarely occurs.
The main side effect is 1-2 days of diarrhoea and sometimes poor appetite, but this usually only occurs when the lymph nodes respond very well to the administered treatment and shrink very quickly. Hypersensitivity reactions are rare and can manifest as itching, redness, bumps, scabs or muscle pain.
The therapy consists of 1 injection into the muscles (or an intravenous infusion) every 2-3 weeks and if successful, the interval can be extended.
However, Oncaspar® is a very expensive medicine with a limited shelf life.
Much research is done on immunotherapeutic alternatives for dogs with a systemic form of lymphoma.
The antibody Rituximab is used in humans but has no effect on canine lymphoma. Multiple studies have been performed on vaccines against lymphoma. The APAVAC® vaccine for lymphoma has resulted in a significant increase of survival rates in some patients and thus seems to be a promising novel treatment. It is always used in conjunction with a polychemotherapy protocol. However, further studies and more patients are required to confirm these results.
Administration of prednisolone can be considered a palliative treatment option. The use of steroids prior the chemotherapy can negatively affect the effect of the chemotherapy.
Surgery can be appropriate when it entails a single lymph node (stage I) or when it’s a single tumour not localized in the lymph nodes. E.g. in case lymphoma is present in the eye or a solitary tumour in the digestive system, complete surgical removal has led to encouraging results.
Radiation therapy, although of limited routine use in the treatment of lymphoma, may be useful in selected cases.
Potential indications are as follows:
- Curative intent for stage I and solitary extranodal disease (e.g. nasal, cutaneous, spinal lymphoma)
- Palliation for local disease (e.g. localized bone involvement, rectal lymphoma, mandibular lymphoma). For lymphoma located in the central nervous system generally the response rate is low and of short duration (a few weeks to months).
- Total body radiation combined with bone marrow or stem cell reconstitution. Bone marrow transplants as described in humans, is not a standard treatment option for companion animals in Europe. After consultation with a radiotherapist and oncologist, it can be decided to irradiate the entire body of the dog, it depends on the case.
- Half-body radiotherapy after chemotherapy-induced remissions or in between chemotherapy cycles.