Cyclical 10-day dosing of melphalan for canine multiple myeloma.

Canine multiple myeloma (MM) is typically treated with melphalan chemotherapy. A protocol with repeated 10-day cyclical dosing of melphalan has been used at our institution but has not been described in the literature. Our objectives were to describe the outcome and adverse events of this protocol in a retrospective case series. We hypothesised the cyclical 10-day protocol would have similar outcomes compared to other reported chemotherapy protocols. Dogs diagnosed with MM that received melphalan treatment at Cornell University Hospital for Animals were identified through a database search. Records were retrospectively reviewed. Seventeen dogs met inclusion criteria. Lethargy was the most common presenting complaint. The median duration of clinical signs was 53 days (range, 2-150 days). Seventeen dogs had hyperglobulinemia with 16/17 having monoclonal gammopathies. Sixteen dogs had bone marrow aspiration and cytology performed at initial diagnosis and plasmacytosis was diagnosed in all. Based on serum globulin concentrations, 10 of 17 dogs (59%) achieved complete response (CR), and 3 dogs (18%) achieved partial response (PR), for an overall response rate of 76%. The median overall survival time was 512 days (range, 39-1065). Retinal detachment (n = 3) and maximum response of CR/PR (n = 13) were associated with overall survival on multivariate analysis (p = .045 and .046, respectively). Adverse events were minimal with diarrhoea being the most reported (n = 6). This cyclical 10-day protocol was better-tolerated with fewer adverse events than with other reported chemotherapy protocols, but response rate was also lower, likely due to a lower dosing intensity.

Description and efficacy of a response-based "QUAD" cyclical hypofractionated palliative-intent radiation protocol in dogs with macroscopic solid tumours: 108 cases.

Palliative-intent radiation therapy can alleviate pain and clinical signs in dogs with cancer, but optimal fractionation scheme is unknown. The objective of this retrospective case series is to evaluate clinical benefit, objective response, adverse effects, and outcomes in 108 dogs with macroscopic solid tumours treated with a cyclical "QUAD" hypofractionated palliative-intent radiation therapy protocol. Median QUAD dose was 14 Gy (14-16 Gy). Median total dose was 28 Gy (14-48 Gy). Clinical benefit rate was 93%, with median onset of subjective palliation 21 days after the first QUAD, lasting a median of 134 days. Tumour volumetric objective response was assessed with CT prior to the third QUAD in 36 dogs, with stable disease in 24 dogs (67%) and partial response in 9 dogs (25%). Sinonasal and oral were the most common tumour locations in 32 and 30 dogs, respectively. Median progression-free survival was 153 days (95% CI 114-200). Median overall survival was 212 days (95% CI 152-259). Number of QUAD cycles completed, clinical benefit achieved, anti-inflammatory received, total radiation dose, time to maximum clinical benefit, and response duration were positively associated with progression-free and overall survival. Acute toxicities were observed in 15 dogs (14%) with 3 high-grade (grade 3) toxicities (3%). Low-grade (grade 1 and 2) late skin and ocular toxicities were observed in 31 dogs (29%), predominantly leukotrichia, alopecia, keratoconjunctivitis sicca, and cataracts. This report demonstrates that QUAD radiation is an alternative protocol to be considered for palliation of dogs with inoperable or advanced stage solid tumours.

Assessing major influences on decision-making and outcome for dogs presenting emergently with nontraumatic hemoabdomen.

OBJECTIVE: To evaluate factors contributing to owner decision-making, satisfaction, and perception of quality of life (QOL) with treatment of dogs with nontraumatic hemoabdomen (NTH). ANIMALS: 132 client-owned dogs. PROCEDURES: An electronic survey was administered to owners of 436 dogs that presented emergently with NTH to a single institution between January 2015 and May 2022. Following survey response, retrospective data collection was performed. RESULTS: Owners reported QOL as the most important factor influencing their decision-making (92%), followed by risk of cancer (57%) or time remaining with their pet (56%). QOL scores were significantly higher with surgery versus those with palliative care (P = .007). Median survival time (MST) was 213 days with surgery and 39 days with palliative care (P = .049). Survival benefit of surgery was lost when considering only dogs with malignant histopathology (MST, 81 days; P = .305). Owners were more likely to be satisfied when they chose surgery over either euthanasia or palliative care (P = .039). Thirty-four owners (26%) second-guessed or were unsure of their decision. CLINICAL RELEVANCE: Surgery resulted in the longest MST with greater perceived QOL and owner satisfaction compared with both palliative care and euthanasia and should therefore be considered highly. The importance of malignancy and survival time on owners' decisions, along with the negative impact of metastasis on survival, underscores the importance of timely preoperative staging. The rate of second-guessing highlights the need for standardization of NTH discussions including treatment options and potential outcomes in order to effectively and efficiently guide treatment of patients with this common presentation.

Metabolic Abnormalities Detected in Phase II Evaluation of Doxycycline in Dogs with Multicentric B-Cell Lymphoma.

Doxycycline has antiproliferative effects in human lymphoma cells and in murine xenografts. We hypothesized that doxycycline would decrease canine lymphoma cell viability and prospectively evaluated its clinical tolerability in client-owned dogs with spontaneous, nodal, multicentric, substage a, B-cell lymphoma, not previously treated with chemotherapy. Treatment duration ranged from 1 to 8 weeks (median and mean, 3 weeks). Dogs were treated with either 10 (n = 6) or 7.5 (n = 7) mg/kg by mouth twice daily. One dog had a stable disease for 6 weeks. No complete or partial tumor responses were observed. Five dogs developed grade 3 and/or 4 metabolic abnormalities suggestive of hepatopathy with elevations in bilirubin, ALT, ALP, and/or AST. To evaluate the absorption of oral doxycycline in our study population, serum concentrations in 10 treated dogs were determined using liquid chromatography tandem mass spectrometry. Serum levels were variable and ranged from 3.6 to 16.6 µg/ml (median, 7.6 µg/ml; mean, 8.8 µg/ml). To evaluate the effect of doxycycline on canine lymphoma cell viability in vitro, trypan blue exclusion assay was performed on canine B-cell lymphoma cell lines (17-71 and CLBL) and primary B-cell lymphoma cells from the nodal tissue of four dogs. A doxycycline concentration of 6 µg/ml decreased canine lymphoma cell viability by 80%, compared to matched, untreated, control cells (mixed model analysis, p < 0.0001; Wilcoxon signed rank test, p = 0.0313). Although the short-term administration of oral doxycycline is not associated with the remission of canine lymphoma, combination therapy may be worthwhile if future research determines that doxycycline can alter cell survival pathways in canine lymphoma cells. Due to the potential for metabolic abnormalities, close monitoring is recommended with the use of this drug in tumor-bearing dogs. Additional research is needed to assess the tolerability of chronic doxycycline therapy.

Live Births from Domestic Dog (Canis familiaris) Embryos Produced by In Vitro Fertilization.

Development of assisted reproductive technologies (ART) in the dog has resisted progress for decades, due to their unique reproductive physiology. This lack of progress is remarkable given the critical role ART could play in conserving endangered canid species or eradicating heritable disease through gene-editing technologies-an approach that would also advance the dog as a biomedical model. Over 350 heritable disorders/traits in dogs are homologous with human conditions, almost twice the number of any other species. Here we report the first live births from in vitro fertilized embryos in the dog. Adding to the practical significance, these embryos had also been cryopreserved. Changes in handling of both gametes enabled this progress. The medium previously used to capacitate sperm excluded magnesium because it delayed spontaneous acrosome exocytosis. We found that magnesium significantly enhanced sperm hyperactivation and ability to undergo physiologically-induced acrosome exocytosis, two functions essential to fertilize an egg. Unlike other mammals, dogs ovulate a primary oocyte, which reaches metaphase II on Days 4-5 after the luteinizing hormone (LH) surge. We found that only on Day 6 are oocytes consistently able to be fertilized. In vitro fertilization of Day 6 oocytes with sperm capacitated in medium supplemented with magnesium resulted in high rates of embryo development (78.8%, n = 146). Intra-oviductal transfer of nineteen cryopreserved, in vitro fertilization (IVF)-derived embryos resulted in seven live, healthy puppies. Development of IVF enables modern genetic approaches to be applied more efficiently in dogs, and for gamete rescue to conserve endangered canid species.