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Seven-year-old, castrated male golden retriever Salvador initially presented in May 2025 for his annual health check. His owners reported a history of mild, intermittent diarrhoea. Physical examination revealed marked bilateral submandibular lymphadenopathy (approximately twice normal size). Salvador was otherwise bright and alert.
Initial diagnostics, including complete blood count (CBC), biochemistry, thoracic radiographs, and abdominal ultrasound, were performed to stage the disease. Findings confirmed a diagnosis of Stage V, Substage B B-cell lymphoma.
Key findings included:
• Infiltration of the liver (confirmed by significantly elevated paired bile acids and in-house cytology).
• Splenic infiltration (confirmed via in-house cytology, showing a monomorphic population of intermediate to large lymphocytes).
• Suspected infiltration of the jejunum, abdominal lymph nodes, and perianal skin.
Salvador’s disease had a guarded prognosis due to three critical factors: confirmed B-cell immunophenotype (generally more favourable than T-cell), advanced Stage V disease, and Substage B (patient systemically unwell, indicated by the diarrhoea and elevated liver values).
Prognostically, dogs with primary hepatic involvement, often accompanying severe gastrointestinal tract (GIT) disease, have a median survival time as short as 63 days, and this poor outcome is compounded by the presence of Substage B disease, which is also associated with reduced response rates and shorter survival7.
Treatment and course
Following an in-depth discussion with the owners, three treatment paths were considered: palliative care, multi-agent chemotherapy, or a single-agent approach. We reviewed the gold-standard CHOP-based protocol, which offers a median survival time (MST) of 10-14 months for B-cell lymphoma5. However, this was declined.
The presence of substantial GIT involvement, elevated liver enzymes, and overall high disease burden significantly increased the risk of life-threatening myelosuppression and severe gastrointestinal side effects.
We initiated therapy with an injection of L-asparaginase (Elspar, 10,000 IU subcutaneous). In addition, Salvador was prescribed prednisolone (40mg/m2 once daily for 14 days, then tapered to 20mg/m2) to induce lympholysis, and Denamarin (S-adenosylmethionine/silybin) to provide hepatic support, which he continued throughout treatment.
At the next recheck, Salvador’s lymph nodes had palpably reduced in size, and liver enzyme levels had improved slightly. However, Salvador now presented with mild, acute, regenerative anaemia (Hematocrit [HCT] 31.6%).
Given the GIT disease and the ulcerogenic potential of high-dose prednisolone, we suspected occult GIT blood loss, either from disease progression or ulceration. We prescribed omeprazole and sucralfate and concurrently reduced the prednisolone dose to mitigate the risk of ulceration.
Relapse and rescue protocols
We had hoped to transition Salvador to lomustine (CCNU), an antineoplastic alkylating agent, but persistent abnormal paired bile acids strictly contraindicated its use due to the high risk of idiosyncratic hepatotoxicity. This decision highlights the importance of hepatic monitoring when considering CCNU.
Instead, the patient was started on procarbazine (50mg PO once daily for 14 days), an alkylating agent, along with a second dose of Elspar (10,000 IU subcutaneous), administered with a 60-minute observation period to monitor for anaphylaxis. At the next recheck, the anaemia had resolved, and he was clinically well, so procarbazine was continued for an additional two weeks.
Unfortunately, at the subsequent recheck, marked generalised lymphadenopathy was noted. Cytology confirmed relapse in the spleen, liver, and submandibular lymph nodes, and bile acids had worsened, indicating resistance to procarbazine and disease progression.
A rescue protocol utilising cyclophosphamide (a cytotoxic, myelosuppressive alkylating agent) was instigated (250mg/m2 IV). To minimise staff exposure to this hazardous drug, we employed the Equashield IV closed-system transfer device and utilised full personal protective equipment (PPE), including disposable gowns, double gloves, and face shields.
The necessity of strict PPE and training for all staff when handling such hazardous drugs in a general practice setting is well-documented6. To prevent sterile haemorrhagic cystitis, an injection of furosemide (4mg/kg) was given prior to administration, and the owners were instructed to ensure frequent urination. As cyclophosphamide is myelosuppressive, prophylactic ciprofloxacin was dispensed for 14 days, with a plan to check the neutrophil nadir (the lowest neutrophil count) seven days post-treatment. Newer protocols, such as THOP, attempt to avoid the toxicities and logistical challenges associated with drugs like cyclophosphamide by replacing them with agents like temozolomide4.
A second cyclophosphamide injection was given 14 days later. Sadly, the disease proved resistant, and Salvador presented with marked generalised lymphadenopathy. Remaining treatment options were: CCNU (Lomustine, considered too high-risk given the severely limited hepatic reserve), Elspar (10,000 IU, administered for palliative debulking), and Melphalan (a cytotoxic, myelosuppressive alkylating agent, dosed at 8 mg PO once daily for 5 days, planned to repeat every 3 weeks).
Six days after starting melphalan (concurrent with prednisolone 20mg daily), Salvador developed acute, severe, haemorrhagic diarrhoea after hours. The local emergency referral centre declined to manage his case due to the cytotoxic drug exposure risk. We managed him in-house with intravenous fluids, sucralfate, omeprazole, and the herbal gastroprotectant slippery elm powder.
The highly messy nature of a large dog with liquid diarrhoea made it exceedingly difficult to ensure minimal staff exposure to the cytotoxic drug, despite best efforts.
Palliative care and outcome
Following this incident, Salvador’s owners opted to discontinue all chemotherapy. They enquired about initiating cannabidiol (CBD) oil, which has anecdotal support for appetite, pain, and nausea management in cancer patients.
We prescribed CBD oil at 2.5mg/kg once daily at night for one week (to assess for excessive sedation), then increased the dose to 2.5mg/kg twice daily (therapeutic range 1-5mg/kg twice daily). The owners anecdotally reported that he slept more comfortably on the CBD oil.
A lengthy quality of life discussion followed. To help the owners monitor comfort levels, they were supplied with the ‘Signs of Pain in Pets’ handout from VIN. Due to reduced appetite, mirtazapine (15mg daily) was prescribed.
Approximately five months after the initial diagnosis, Salvador’s owners noted significant dysphagia caused by enormously increased submandibular lymph node size, and the decision was made for a peaceful euthanasia at home.
Dr Sue Robertson BVSc MACVS (Feline Medicine)
Central New Farm Veterinary Surgery
Dr Sue Robertson graduated from the University of Queensland in 1991, and has worked in inner-city veterinary practices, in Melbourne and Brisbane, ever since.
Her special interest areas include feline medicine, gastroenterology and dermatology.
Dr Robertson obtained an MANZCVS in Feline Medicine and passed the NAVLE/CPE exams with a view to working in Canada.
