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Despite an initial strong response in most dogs with multicentric lymphoma treated with chemotherapy, relapse remains common. There is no clearly superior first rescue protocol described either for resistant or relapsed canine multicentric lymphoma. The objectives of this study were to assess clinical response and outcomes for canine multicentric lymphoma treated with first rescue protocols. The secondary objective was to assess prognostic variables for dogs undergoing these protocols. This was a bi-institutional retrospective cohort study. Two hundred and sixty-five dogs were treated with first rescue chemotherapy, including anthracycline-based combination chemotherapy (CHOP-like, n = 50), nitrosourea alkylating agent-rich chemotherapy (n = 45), anthracycline-based or related compound chemotherapy (n = 34), or nitrosourea single-agent chemotherapy (n = 136). The overall median progression free survival time of first rescue protocol was 56.0 days (0-455 days). Important prognostic factors identified for first rescue protocol included the attainment of a complete response to the first rescue chemotherapy (p < .001), the use of a CHOP-like first rescue protocol (p = .009), duration of first remission (HR 0.997, p = .028), and if prednisolone was included in the first rescue protocol (HR 0.41, p = .003). Adverse events (AE) were common, with 81.1% of dogs experiencing at least one AE during first rescue chemotherapy. This study highlights the need for improved first rescue therapies to provide durable remission in canine resistant or relapsed lymphoma., (© 2024 John Wiley & Sons Ltd.)

Prior studies have identified high CD25 expression in canine diffuse large B-cell lymphoma as a negative prognostic indicator. The objective of this retrospective study was to evaluate CD25 expression as a prognostic indicator in dogs with B-cell lymphoma (BCL) diagnosed with commonly used noninvasive diagnostics (cytology and flow cytometry [FC]) and treated with CHOP chemotherapy. Lymph node aspirates from 57 dogs with cytologic diagnosis of lymphoma composed of intermediate to large lymphocytes were analysed with FC. Percentage of neoplastic B-cells expressing CD25 and median fluorescence intensity (MFI) of CD25 were measured. Relationships of CD25 percent positivity and MFI to progression free survival (PFS) and survival time were evaluated. Median survival time (MST) of all dogs was 272 days (95% CI, 196-348 days) and median PFS was 196 days (95% CI, 172-220 days). Higher percentage of B-cells positive for CD25 was associated with decreased risk of death in multivariable analysis (p = .02). Dogs with higher CD25 positivity had longer MST and PFS than dogs with lower CD25 positivity (318 days versus 176 days and 212 days versus 148 days, respectively), but these differences were not significant. CD25 MFI was not significantly associated with outcome. Based on the results of this study, the association of CD25 expression and prognosis in dogs with BCL diagnosed using noninvasive methods should be interpreted with caution. Further evaluation, with studies that include histopathologic differentiation of lymphoma subtypes, is needed., (© 2022 John Wiley & Sons Ltd.)

We examined the efficacy and adverse events of continuous l-asparaginase administration in dogs with large cell lymphoma of presumedgastrointestinal (GI) origin. We retrospectively reviewed medical records of dogs with large cell lymphoma of presumed GI origin treated with continuous l-asparaginase administration from 2009 to 2018. We collected information on the signalment, lesion site, complete blood count, serum biochemical profile, diagnostic imaging findings, cytological and histopathological findings, immunophenotype, l-asparaginase administration frequency, treatment response, adverse events, rescue protocol, and patient outcomes. Clinical outcomes were assessed using medical records or by contacting the owner or referring veterinarian. Thirty-two dogs with large cell lymphoma of presumed GI origin received weekly l-asparaginase administration. The median number of l-asparaginase injections was seven (range: 1-30). Although two of the 32 dogs had GI toxicity of grade 3 or higher, none developed a hypersensitivity reaction. The response rate based on ultrasonographic findings was 18/32 (56%) and that based on clinical signs was 30/32 (94%). The median overall progression-free survival was 50 days (range: 2-214 days), and median overall survival was 147 days (range: 2-482 days). Adverse events associated with continuous l-asparaginase administration were rare. Clinical signs at diagnosis improved in most cases. Based on these results, continuous l-asparaginase administration appears to be a reasonable treatment option for dogs with large cell lymphoma of presumed GI origin., (© 2021 John Wiley & Sons Ltd.)

We report a precision medicine platform that evaluates the probability of chemotherapy drug efficacy for canine lymphoma by combining ex vivo chemosensitivity and immunophenotyping assays with computational modelling. We isolated live cancer cells from fresh fine needle aspirates of affected lymph nodes and collected post-treatment clinical responses in 261 canine lymphoma patients scheduled to receive at least 1 of 5 common chemotherapy agents (doxorubicin, vincristine, cyclophosphamide, lomustine and rabacfosadine). We used flow cytometry analysis for immunophenotyping and ex vivo chemosensitivity testing. For each drug, 70% of treated patients were randomly selected to train a random forest model to predict the probability of positive Veterinary Cooperative Oncology Group (VCOG) clinical response based on input variables including antigen expression profiles and treatment sensitivity readouts for each patient's cancer cells. The remaining 30% of patients were used to test model performance. Most models showed a test set ROC-AUC > 0.65, and all models had overall ROC-AUC > 0.95. Predicted response scores significantly distinguished (P < .001) positive responses from negative responses in B-cell and T-cell disease and newly diagnosed and relapsed patients. Patient groups with predicted response scores >50% showed a statistically significant reduction (log-rank P < .05) in time to complete response when compared to the groups with scores <50%. The computational models developed in this study enabled the conversion of ex vivo cell-based chemosensitivity assay results into a predicted probability of in vivo therapeutic efficacy, which may help improve treatment outcomes of individual canine lymphoma patients by providing predictive estimates of positive treatment response., (© 2020 ImpriMed, Inc. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

Vincristine is included in vincristine, cyclophosphamide, doxorubicin and prednisone (CHOP) chemotherapy protocols, which are the gold-standard treatment for high-grade canine lymphoma. Vincristine can result in relatively high rates of gastrointestinal toxicity, whereas vinblastine is generally well tolerated and thus may represent an under-utilized and minimally toxic alternative to vincristine. Our objective was to determine the response rate and toxicity associated with a single dose of vinblastine administered to dogs with treatment-naïve, intermediate to large-cell, multicentric lymphoma. Twenty client-owned dogs were enrolled with signed owner consent. A Simon's minimax, phase II, two-stage trial was performed to test the efficacy of vinblastine administered at 2 mg/m 2 IV followed by a pilot trial of vinblastine at 2.5 mg/m 2 . No dogs were administered concurrent steroids or other chemotherapy. One out of 14 dogs receiving vinblastine at 2 mg/m 2 demonstrated a partial response. Three out of five dogs demonstrated a partial response to vinblastine at 2.5 mg/m 2 . Gastrointestinal toxicity was infrequent and low grade for both groups. The majority of dogs (80%) in the 2.5 mg/m 2 dosing group developed neutropenia 1-week post administration. Vinblastine was well tolerated but minimally efficacious at a dose of 2 mg/m 2 IV in dogs with treatment-naive, multicentric lymphoma. Because of poor response rates, treatment at this dose is not recommended. A small subset of dogs administered 2.5 mg/m 2 had significantly improved response rates (P = 0.04), suggesting that higher doses may have improved efficacy, although further research is indicated to confirm these preliminary findings., (© 2018 John Wiley & Sons Ltd.)

Glutathione S-transferase-theta (GSTT1) is a carcinogen detoxification enzyme, and low activity variants are associated with lymphoma in humans. We recently found a variant in the 3' untranslated region (UTR) of canine GSTT1, *101&#95;102insT, which was predicted to change miRNA binding and was found in 5 of 17 golden retriever (GR) dogs with lymphoma but none of 14 healthy GRs. The aim of this study was to determine whether this variant led to decreased GSTT1 expression and was a discernible risk factor for lymphoma within the GR breed. On resequencing, *101&#95;102insT appeared to be in complete linkage disequilibrium with 3 additional 3'UTR variants, leading to the inferred haplotype *3T>C; *101&#95;102insT; *190C>A; *203T>C. In canine livers that were heterozygous for this variant haplotype, GSTT1 protein expression was significantly lower compared to the reference haplotype (densitometry .40 vs .64, P = .022), and GSTT1 transcript levels by qPCR were also significantly lower (fold difference .52, P = .012), without evidence of substantial allelic expression imbalance. The variant haplotype led to >50% decrease in expression in vitro (.31 ± .07 vs .64 ± .19; P = .019). We found no significant difference in minor allele frequencies between 71 GR dogs with lymphoma (MAF .162) and 33 healthy age-matched controls (MAF .136, P = .69). Our results indicate that the variant GSTT1 3'UTR haplotype containing *101&#95;102insT reduces gene expression, which could lead to impaired carcinogen detoxification, but was not a detectable risk factor for lymphoma in GR dogs., (© 2017 John Wiley & Sons Ltd.)

The modified Glasgow Prognostic Score (mGPS) assigns a numerical value (0-2) from pre-treatment serum concentrations of C-reactive protein (CRP) and albumin to predict patient outcome. CRP and albumin were evaluated in 77 untreated dogs with lymphoma to determine the relationship of mGPS to clinicopathological parameters and whether it could predict progression-free (PFS) and overall survival (OS) in treated dogs. mGPS distribution was significantly associated with clinical stage, substage b, weight loss, gastrointestinal disturbances and lethargy at presentation. On univariate analysis, mGPS was significantly associated with OS and PFS, with shorter median survival times for mGPS 2 compared to mGPS 0 and 1 combined. Hypoalbuminaemia significantly reduced OS and PFS, however increased CRP had no effect. Only clinical stage was significantly associated with OS and PFS on both univariate and multivariate analysis. mGPS has potential prognostic value for canine lymphoma , but further studies are needed., (© 2017 John Wiley & Sons Ltd.)

This study describes epidemiologic, clinical, macro- and microscopic tumour characteristics and outcome in 97 cats with subcutaneous lymphoma, an uncommon variant of feline extranodal lymphoma. Middle-aged (median 11 years), male (60.8%), Domestic Shorthair cats (89.7%) were commonly affected. Most tumours presented as a painless, firm, subcutaneous nodule or mass, with predilection to the lateral thoracic or abdominal wall, and the interscapular region. Deep subcutaneous invasion with extension into superficial or underlying tissues, extensive central areas of necrosis and peripheral inflammation were characteristic histopathological findings. Prevalence of retroviral infection was low. Local relapses after therapy were common (43.5%), and 32.2% had distant involvement later in course. Median overall survival was 148 days. Subcutaneous lymphoma should be considered a rare but important differential diagnosis for a subcutaneous mass in cats. Tumours show an aggressive biological behaviour. Treatment options including prognosis should be investigated in further studies., (© 2014 John Wiley & Sons Ltd.)

Standard of care treatment of dogs with multicentric lymphoma includes combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP); however, owners may be hesitant to commit the resources necessary to complete a lengthy, multi-drug protocol. One hundred thirty-four client-owned dogs with multicentric lymphoma were treated with a 15-week CHOP chemotherapy protocol. The overall response rate was 98% with 104 dogs experiencing a complete response (CR). The median progression-free survival (PFS) time for all dogs was 176 days, and the median disease-specific overall survival time was 311 days. Prognostic factors identified on multivariate analysis as significant for PFS included substage, immunophenotype, hospitalization for adverse events, need for dose reduction, presence of neutrophilia at diagnosis, presence of anemia and experiencing a CR as best response to therapy. In conclusion, this protocol may be a viable alternative to CHOP protocols using a larger number of treatments., (© 2015 John Wiley & Sons Ltd.)

Glutathione-S-transferase enzymes (GSTs) play an important role in the detoxification of environmental carcinogens. Defective GST genotypes are over-represented in human cancers; in particular, low activity GSTT1 genotypes are risk factors for non-Hodgkin lymphoma. We hypothesized that defective GSTT1 genotypes would be associated with lymphoma risk in dogs. To address this, we resequenced the exons, splice junctions, and 3'-UTR of canine GSTT1 in dogs with lymphoma (n = 93) and age-matched unaffected dogs (n = 86). Of 27 canine GSTT1 variants identified, the I2+28 G>A was significantly associated with lymphoma [odds ratio (OR) 6.26, 95% confidence interval (CI), 1.77-22.2], with the AA genotype found in 18.3% of affected dogs but only 3.5% of controls (P = 0.002). This intronic variant was predicted to perturb GSTT1 mRNA splicing, and may increase lymphoma risk by impairing detoxification of environmental chemicals. Confirmation of this finding in a larger population of dogs may support the inclusion of GSTT1 genotyping in epidemiologic studies of canine lymphoma risk., (© 2012 John Wiley & Sons Ltd.)