Serum C-reactive protein concentrations in dogs with multicentric lymphoma undergoing chemotherapy

OBJECTIVE: To determine whether serum C-reactive protein (CRP) concentration is high in dogs with multicentric lymphoma, whether CRP concentration changes in response to chemotherapy, and whether CRP concentration can be used as a marker for relapse in dogs with multicentric lymphoma. DESIGN: Cohort study. ANIMALS: 20 dogs with multicentric lymphoma and 8 healthy control dogs undergoing chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP) or with vincristine, cyclophosphamide, methotrexate, and L-asparaginase (VCMA) and 20 other healthy dogs. PROCEDURES: Serum CRP concentration was measured weekly during the first month of chemotherapy and then at 3-week intervals until relapse in dogs with multicentric lymphoma, weekly for 16 weeks in healthy dogs undergoing chemotherapy, and once in the healthy dogs not undergoing chemotherapy. RESULTS: For both groups of dogs with lymphoma, mean serum CRP concentration during week 1 (prior to treatment) was significantly higher than mean concentrations following induction of chemotherapy and at the time of relapse. Mean serum CRP concentration in the healthy dogs undergoing chemotherapy was not significantly different at any time from mean concentration for the healthy dogs not undergoing chemotherapy. No significant differences were observed between dogs treated with CVP and dogs treated with VCMA. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that serum CRP concentration is high in dogs with multicentric lymphoma but that serum CRP concentration is not a useful marker for relapse and that chemotherapy itself does not affect serum CRP concentration.     

Gastrointestinal parasites of shepherd and hunting dogs in the Serres Prefecture, Northern Greece

A total of 281 faecal samples from owned shepherd and hunting dogs were collected in the Serres Prefecture, Northern Greece and were examined for the presence of intestinal parasites. The overall prevalence of parasitism was 26% and the 11 species found were: Toxocara canis (12.8%), Trichuris vulpis (9.6%), Giardia spp. (4.3%), Isospora (Cystoisospora) spp. (3.9%), Ancylostoma/Uncinaria spp. (2.8%), Cryptosporidium spp. (2.8%), Alaria alata (2.5%), Strongyloides stercoralis (1.8%), Angiostrongylus vasorum (1.1%), Toxascaris leonina (0.7%) and Dipylidium caninum (0.3%). The prevalence of T. canis and Isospora (Cystoisospora) spp. was significantly higher in young than in adult dogs (p < 0.05). There was no significant difference in prevalence between genders, except for T. canis, which was more common in male dogs (p < 0.05).     

Faecal microbiota in dogs with multicentric lymphoma

Malignant lymphoma B‐cell type is the most common canine haematopoietic malignancy. Changes in intestinal microbiota have been implicated in few types of cancer in humans. The aim of this prospective and case‐control study was to determine differences in faecal microbiota between healthy control dogs and dogs with multicentric lymphoma. Twelve dogs affected by multicentric, B‐cell, stage III‐IV lymphoma, and 21 healthy dogs were enrolled in the study. For each dog, faecal samples were analysed by Illumina sequencing of 16S rRNA genes and quantitative PCR (qPCR) for selected bacterial groups. Alpha diversity was significant lower in lymphoma dogs. Principal coordinate analysis plots showed different microbial clustering (P = .001) and linear discriminant analysis effect size revealed 28 differentially abundant bacterial groups in lymphoma and control dogs. The qPCR analysis showed significant lower abundance of Faecalibacterium spp. (q < .001), Fusobacterium spp. (q = .032), and Turicibacter spp. (q = .043) in dogs with lymphoma compared with control dogs. On the contrary, Streptococcus spp. was significantly higher in dogs with lymphoma (q = .041). The dysbiosis index was significantly higher (P < .0001) in dogs with lymphoma. In conclusion, both sequencing and qPCR analyses provided a global overview of faecal microbial communities and showed significant differences in the microbial communities of dogs presenting with multicentric lymphoma compared with healthy control dogs.     

Comparison of COAP and UW-19 protocols for dogs with multicentric lymphoma

BACKGROUND: Various chemotherapy protocols for treating lymphoma in dogs have been published; however, comparison of protocols from different studies is difficult, especially when evaluating survival time and toxicoses. HYPOTHESIS: The choice of COAP (C, cyclophosphamide; O, vincristine; A, cytosine arabinoside; P, prednisone) and a modified University of Wisconsin 19-week (UW-19) induction protocol has no influence on overall survival times in dogs with lymphoma. ANIMALS: One hundred and one dogs with multicentric lymphoma. METHODS: Retrospective study (2001-2006). Dogs induced with either an 8-week COP-based protocol (C, cyclophosphamide; O, vincristine; and P, prednisone) with maintenance therapy (COAP group) or a 19-week CHOP (C, cyclophosphamide; H, doxorubicin; O, vincristine; and P, prednisone) based protocol (UW-19 group) were compared in terms of the duration of first remission, survival time, toxicoses, and cost. RESULTS: There were 71 dogs in the COAP group and 30 dogs in the UW-19 group. Various protocols were used after the first relapse. The median duration of the first remission for the COAP and UW-19 groups were 94 days (range, 6-356 days) and 174 days (28-438 days), respectively (P < .01). The median survival times for dogs in the COAP and UW-19 groups were 309 days (6-620 days) and 275 days (70-1102+ days), respectively (P = .09). Dogs in the COAP group had a hazard ratio of 1.9 (95% CI 1.1-3.4) for death relative to the UW-19 group (P = .03), after controlling for the confounders (World Health Organization clinical stage, age, sex, use of doxorubicin during reinduction). The severity of neutropenia and gastrointestinal toxicoses were significantly higher in the UW-19 group than in the COAP group (P = .01 and P < .01, respectively). CONCLUSION AND CLINICAL IMPORTANCE: Use of a long-term doxorubicin-containing sequential combination chemotherapy protocol is associated with a decreased risk of relapse and death relative to a non-doxorubicin-containing protocol.     

Hyperferritinemia is associated with short survival time in dogs with multicentric lymphoma

In the present study, we examined the relationship between serum ferritin concentration before treatment and survival time in dogs with multicentric lymphoma. Eighteen dogs with multicentric lymphoma were enrolled in the study. When the dogs were classified into high and low ferritin groups on the basis of their serum ferritin concentration (3,000 ng/ml cut-off value), the median survival time of dogs with high concentrations (≥3,000 ng/ml, n=7) was 40 days, whereas it was 360 days among dogs with low concentrations (<3,000 ng/ml, n=11). This difference was statistically significant (P=0.001). This finding suggests that the initial high level of serum ferritin indicates short survival time in dogs with multicentric lymphoma. Large-scale research is necessary to confirm this finding.     

Prevalence of intestinal parasites in dogs from public shelters in Serbia

Data on endoparasitic infections in dogs from dog shelters in Southeastern Europe are limited; thus, this study aimed to add to the existing knowledge on this topic by reporting on the prevalence of intestinal parasites in dogs from public dog shelters in the Republic of Serbia. In 2017 and 2018, individual and pooled fecal samples, were collected from 1267 dogs from six shelters. All samples were qualitatively examined for parasites using flotation tests. Seven taxa of intestinal parasites were identified: Cystoisospora spp., ascarids: Toxocara canis and Toxascaris leonina, hookworms, Trichuris vulpis, taeniids and Dipylidium caninum. The overall prevalence of intestinal parasites was 58. 3 % (78. 1 % in young dogs and 53.1 % in adult dogs). The parasites detected in both young (<1 year old) and adult dogs (>1 year old) were Cystoisospora spp. (20 % and 4.9 %), T. canis (33.5 % and 14.7 %), T. leonina (7.7 % and 2.3 %), and hookworms (16.9 % and 15 %), respectively. However, T. vulpis (9.6 %), taeniids (1.3 %), and D. caninum (5.4 %) were detected only in adult dogs. In the Belgrade shelter, young dogs had a higher prevalence of endoparasitic infections (18.9 %, 49/260) than adult dogs (14.8 %, 149/1007). In the Subotica, Jagodina and Niš shelters, young dogs had significantly higher (p < 0.001 and p < 0.05, respectively) prevalence of endoparasitic infections (10 %, 12.3 % and 14.6 %) than adult dogs (5.3 %, 8 % and 7.2 %). These results will be useful for establishing health care programs in dog shelters and implementing effective strategies for the control of intestinal parasites.     

Influence of chemotherapy for lymphoma in canine parvovirus DNA distribution and specific humoral immunity

In man, the combination of cancer and its treatment increases patients’ susceptibility to opportunistic infections, due to immune system impairment. In veterinary medicine little information is available concerning this issue. In order to evaluate if a similar dysfunction is induced in small animals undergoing chemotherapy, we assessed the complete blood count, leukocytic, plasma and fecal canine parvovirus (CPV) viral load, and anti-CPV protective antibody titers, in dogs with lymphoma treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) protocol, before and during chemotherapy.There was no evidence of decreased immune response, either at admission or after two chemotherapy cycles, indicating that the previously established immunity against CPV was not significantly impaired, supporting the idea that immunosuppression as a result of hematopoietic neoplasms and their treatment in dogs requires further investigation and conclusions cannot be extrapolated from human literature.     

Fractionated oral dosing and its effect on cyclophosphamide pharmacokinetics in dogs with high-grade multicentric lymphoma

Cyclophosphamide (CP) is an alkylating agent commonly included in multi-drug treatment protocols for canine cancer. As a prodrug, CP requires hepatic metabolism for activation to the intermediate compound 4-hydroxycyclophosphamide (4-OHCP) which then spontaneously forms alkylating phosphoramide mustard. CP is frequently administered in a fractionated manner, with the total dose given over multiple days. CP is reported to cause auto-induction of metabolism in humans, with faster CP clearance and relatively increased 4-OHCP formation following fractionated versus bolus dosing, however canine pharmacokinetic studies of CP dose fractionation are lacking. The study objective was to evaluate the pharmacokinetics of fractionated oral CP dosing at a dose of 200–250 mg/m² over 3 to 4 days in a prospectively identified population of cancer-bearing dogs. Plasma concentrations of CP and 4-OHCP were measured by ultra-high performance liquid chromatography tandem-mass spectrometry in eight dogs following the first and last doses to assess for auto-induction of CP metabolism. No significant difference in the rate of CP elimination between first and last doses were detected (0.73 ± 0.46 vs. 1.22 ± 0.5 h⁻¹; p = .125). Additionally, no significant difference in dose-normalized 4-OHCP exposure was identified between first and last doses (5.9 ± 2.1 vs. 7.9 ± 6.4 h × ng/ml; p = .936). These results suggest that fractionated dosing may not increase exposure to the active metabolite of CP in dogs as it does in humans. As such, standard bolus dosing and fractionated dosing may be equivalent in terms of bio-activation of CP in dogs administered a dose of 200–250 mg/m².     

Single agent gemcitabine chemotherapy in dogs with spontaneously occurring lymphoma

BACKGROUND: Gemcitabine has been shown to be effective as a single agent in a variety of tumors including nonHodgkin's lymphoma. Its use in veterinary medicine has been limited and to date this drug has not been used as a first-line therapy in dogs with lymphoma. HYPOTHESIS: Gemcitabine as a single agent may be efficacious in dogs presented for the first time with lymphoma. ANIMALS: Twenty-four dogs with spontaneously occurring lymphoma. METHODS: All dogs were clinically staged and given gemcitabine at 400 mg/m(2) over a 30-minute intravenous infusion weekly for 3 weeks and then given 1 week off treatment before starting a second cycle. RESULTS: A single dose of gemcitabine lowered both neutrophil count (decrease in mean neutrophil count from 10,640 cells/ microL to 3,140 cells/microL) and platelet count (decrease in mean platelet count from 201,290 cells/microL to 139,190 cells/microL) 7 days after administration. Consequently gemcitabine dosage was reduced at the second treatment in 8 of 21 dogs or a dose delay of 1-7 days and a reduction of dosage was used in 7 of 21 dogs. Seven dogs completed the assigned 4-week cycle. Two of these dogs had progressive disease and 5 had stable disease. No objective responses were seen in dogs treated with a second cycle of gemcitabine. CONCLUSIONS AND CLINICAL IMPORTANCE: Gemcitabine administration as a single agent resulted in hematologic toxicity and did not reduce lymphoma burden. If gemcitabine is to be used in veterinary medicine, additional prospective pharmacologic studies should be done to determine the appropriate dosage, regimen, and schedule of use before it can be recommended for use in the treatment of dogs with lymphoma as a single agent.     

Utility of a multiple serum biomarker test to monitor remission status and relapse in dogs with lymphoma undergoing treatment with chemotherapy

A blinded retrospective study was conducted to investigate remission and recurrence of lymphoma in dogs receiving chemotherapy. The objective was to compare clinicians' assessment using palpation and cytology to the results of serum biochemical tests for haptoglobin (Hapt) and C‐reactive protein (C‐RP). These biochemical test results were combined using a diagnostic algorithm developed using data from 344 individual dogs. This multivariate approach, termed the canine lymphoma blood test (cLBT), was used to follow 57 dogs during and after treatment. cLBT of remission and recurrence compared well with clinicians' assessment and differentiated dogs in remission and those with recurring disease before appearance of lymphadenopathy (P < 0.001). The cLBT demonstrated prognostic potential based on pre‐treatment values on dogs with shorter survival times and on those achieving the lowest cLBT score during treatment that showed longer survival times. The test, therefore, demonstrates potential to assist in monitoring treatment of canine lymphoma.     

Serum amyloid A is not a marker for relapse of multicentric lymphoma in dogs

BACKGROUND: Serum amyloid A (SAA) is an acute phase protein whose concentration increases in inflammatory, infectious, and neoplastic conditions in animals and human beings. Multicentric lymphoma is a common cancer in dogs, and chemotherapy is indicated to attain long-term survival. However, frequent relapses lead to changes in chemotherapeutic protocols. OBJECTIVES: The aims of this study were to evaluate SAA as a marker for relapse of multicentric lymphoma in dogs and to determine whether chemotherapy induces changes in the concentration of SAA during treatment. METHODS: SAA was measured by an ELISA test in healthy control dogs (n=20), in healthy dogs receiving chemotherapy (n=8), and in dogs with lymphoma (n=20). All dogs receiving chemotherapy were randomly assigned to 2 treatment groups, one receiving cyclophosphamide, vincristine, and prednisone (CVP) and the other receiving vincristine, cyclophosphamide, methotrexate, and L-asparaginase (VCMA) protocols. SAA concentration was determined before chemotherapy at weeks 1-4 in healthy dogs receiving chemotherapy and in dogs with lymphoma, then every 3 weeks for 4 months in healthy dogs, and at relapse and in the sample prior to relapse in dogs with lymphoma. SAA was measured only once in the healthy control dogs. Results were analyzed using repeated measures ANOVA followed by Tukey multiple comparison tests to compare groups and weeks of treatment. RESULTS: Mean SAA concentration was significantly higher in dogs with lymphoma before chemotherapy compared with healthy and chemotherapy control dogs. No increase in SAA concentration was found at relapse. No differences were observed in SAA concentration based on type of chemotherapy protocol. CONCLUSIONS: SAA is not a marker of relapse in dogs with multicentric lymphoma, nor does chemotherapy regimen affect SAA concentration.     

Association between weight change during initial chemotherapy and clinical outcome in dogs with multicentric lymphoma

The majority of the known prognostic factors in dogs with lymphoma have been evaluated before treatment commences or at the time of diagnosis. Prognostic factors evaluated during the initial phase of treatment are less described but may provide important clinical information. In this retrospective study, 82 canine lymphoma patients were categorized according to the weight change between diagnosis and after 5 weeks of chemotherapy. Dogs that gained greater than 5% or lost greater than 5% of initial body weight were categorized as increased‐ or decreased‐weight groups, respectively. Those in which weight changed less than 5% were categorized as the maintained‐weight group. The median progression‐free survival (PFS) in the increased‐weight group, maintained‐weight group and decreased‐weight group was 226, 256 and 129 days, respectively. The decreased‐weight group had significantly shorter PFS than the increased and maintained groups (P = .023, P = .003, respectively). The median survival time (ST) in the increased‐weight group, maintained‐weight group and decreased‐weight group was 320, 339 and 222 days, respectively. There was no significant difference in ST among the three groups (P = .128). In Cox‐regression results, weight change group and initial body weight were significant risk factors associated to PFS (P = .007, P = .001, respectively) while only patient's initial body weight was a significant risk factor to ST (P = .013). In conclusion, evaluation of initial body weight and weight changes over time can provide valuable information regarding PFS and ST in dogs with multicentric lymphoma.     

Ocular and multicentric lymphoma in a young racehorse

A 6-year-old thoroughbred gelding was presented with a history of blepharospasm and opacity in the OS of 1 weeks' duration. Ophthalmic examination findings were consistent with acute uveitis in the OS, and traditional treatment was initiated with systemic antibiotics and anti-inflammatory drugs, topical mydriatics, and corticosteroids. During the total treatment period of 4 weeks response to treatment was weak and the horse developed further problems such as cellulitis of the right hind limb with fever and eventually weight loss and dependent edema. Blood work was indicative of liver disease. Abdominal sonography revealed severe splenomegaly and slight hepatomegaly, and a liver biopsy confirmed malignant T-cell lymphoma. The horse was euthanized due to deteriorating general condition and subsequently underwent postmortem examination. Necropsy and histologic examination revealed a multicentric lymphoma with involvement of spleen, mesenteric lymph nodes, and OU.
The findings in this case demonstrate that the differential diagnosis of intraocular and systemic lymphoma should be considered in any horse presenting with anterior uveitis, especially when uveitis is unresponsive to treatment and when additional systemic signs of illness such as lethargy, fever, weight loss, or dependent edema arise.
Cytological examination of aqueous humor may provide a rapid diagnosis of intraocular lymphoma in eyes with clinical uveitis.     

Prevalence and risk factors associated with intestinal parasites in pigs in Chongqing, China

From 2007 to 2009, the prevalence of intestinal parasites was investigated in intensive and extensive pig farms in Chongqing, China. A total of 2971 samples from both sexes and five age categories (breeding boars, breeding sows, fatteners, growers and weaners) were evaluated by standard methods for the presence of helminth ova and protozoan oocysts, cysts and/or trophozoites. Of the 2971 pigs sampled, 362(12.18%) were infected with Ascaris suum, 301(10.13%) with Trichuris suis, 301(10.13%) with Oesophagostomum spp., 491(16.53%) with Eimeria spp., 149(5.02%) with Isopora suis, 677(22.79%) with Balantidium coli and 196(6.60%) with Cryptosporidium spp. Growers had the highest infection rate while breeding boars had the lowest among the five age categories. B. coli was the most common protozoan in all pig age groups. Pigs infected with multiple parasites were common. Risk factors such as management methods, seasons, ages, etc. can influence the infection rate to a certain degree. This investigation provides relevant data about risk factors for pig farmers, thus allowing them to make more appropriate antiparasitic treatments according to farm conditions and local climate in Chongqing.     

Adjuvant carboplatin and gemcitabine combination chemotherapy postamputation in canine appendicular osteosarcoma

Background: Appendicular osteosarcoma (OSA), the most common bone tumor in dogs, is typically treated by amputation and adjuvant chemotherapy. Despite numerous efforts, the median survival time (MST) for dogs receiving a platinum compound, doxorubicin, or a combination of these remains at 8–12 months. Evidence from studies in mice suggests that gemcitabine has activity against OSA in vivo. Our preliminary work demonstrated that the addition of low‐dosage (10 mM) gemcitabine to carboplatin resulted in synergistic inhibition of OSA cell viability in vitro. Objective: The purpose of the following study was to determine whether the addition of low‐dosage (2 mg/kg) gemcitabine to carboplatin chemotherapy in dogs with OSA after amputation would improve MST over carboplatin monotherapy. Animals: Fifty dogs with histologically confirmed appendicular OSA. Methods: Dogs were treated prospectively with amputation and up to 4 dosages of carboplatin and gemcitabine in combination every 3 weeks. Results: The chemotherapeutic regimen was well tolerated with only 5 episodes of grade 3 or 4 hematologic toxicity. The median disease‐free interval (DFI) was 203 days and the MST was 279 for all dogs in this study. The 1‐ and 2‐year survival rates were 29.5 and 11.3%, respectively. Dogs with proximal humeral OSA had a shorter median DFI (P= .04) compared with dogs with OSA in other locations. Conclusions and Clinical Importance: These results are comparable to those reported for carboplatin monotherapy indicating that the addition of gemcitabine to carboplatin in dogs with appendicular OSA does not appear to improve outcome.     

Prevalence of intestinal parasites in shelter and hunting dogs in Catalonia,Northeastern Spain

To compare the prevalence of intestinal parasites in shelter and hunting dogs in Catalonia, Northeastern Spain, fresh faecal samples from 81 shelter dogs and 88 hunting dogs were collected and analysed by faecal flotation. The overall prevalence of intestinal parasites was 71.6% in each population. In the shelter dog group, 67.9% of dogs were positive for intestinal protozoa and 9.8% were positive for helminths. In the hunting dog group, 20.4% of dogs were positive for intestinal protozoa and 63.6% were positive for helminths. A subset of Giardia-positive samples was evaluated by PCR; Giardia assemblages C or D were detected. These results suggest that comprehensive parasite control measures should be implemented in both shelter and hunting dogs in Catalonia.     

The immunophenotype of peripheral blood lymphocytes in clinically healthy dogs and dogs with lymphoma in remission

Lymphoma is a common cancer of dogs that frequently is treated with chemotherapy or radiation therapy. Response to therapy is variable and currently available diagnostic tests do not reliably predict response to therapy. Treatment for lymphoma often results in lymphopenia, but it is unknown whether the changes in circulating lymphocytes result from generalized or specific reduction of lymphocytes. In this study, blood lymphocytes from 12 clinically healthy dogs, 10 dogs in remission because of treatment for B-cell lymphoma, and 8 dogs in remission from T-cell lymphoma were analyzed by flow cytometry by using a panel of 20 antibodies reactive with canine leukocyte antigens. Results identified similar lymphocyte parameters in treated dogs regardless of the type of lymphoma. Treated dogs had >50% reduction in blood lymphocyte concentration, and an absolute decrease in most subsets of lymphocytes. Both groups of treated dogs had relative increases in the proportion of CD3+, T-cell receptor (TCR)αβ+, and CD90+ lymphocytes, and a decreased proportion of CD45RA+ cells. In addition, dogs with T-cell lymphoma in remission had a significant increase in the proportion of CD49d+ lymphocytes. These findings were interpreted as representing likely suppression of lymphocyte regeneration by chemotherapy, with a relative increase in the proportion of memory over naïve lymphocytes. Lack of correlation with the T- or B-cell origin of the initial lymphoma suggested that, by using flow cytometric methods, residual circulating neoplastic cells could not be detected. However, the changes in the lymphocyte profile of dogs treated with chemotherapy may have relevance to their immunocompetence.     

MRI features of CNS lymphoma in dogs and cats

The magnetic resonance (MR) imaging features of central nervous system lymphoma in eight dogs and four cats are described. Intracranial lesions affected the rostrotentorial structures in six dogs and caudotentorial structures in two cats. Lesions affected the spinal cord in two dogs and in two cats. One dog and one cat with intracranial lymphoma had signs of local extracranial extension and lymphadenopathy. Lesions were considered extraparenchymal in four dogs and three cats, intraparenchymal in two dogs and one cat, and appeared to have both intra- and extraparenchymal components in two dogs. All lesions were hyperintense in T2-weighted images when compared to white matter, most were hypointense in T1-weighted images (7/12), and most were hyperintense in fluid-attenuated inversion recovery (FLAIR) images (5/9). When compared to grey matter, these lesions appear either isointense (5/12) or hyperintense (7/12) on T2-weighted images, half of them were hypointense in T1-weighted images (6/12), and most were isointense in FLAIR images (7/9). Lesion margins were usually indistinct in T2-weighted images (10/12) and had perilesional hyperintensity in FLAIR images (7/9). The majority of lesions (10/12) had abnormal meninges around the lesion and half (6/12) had generalized contrast enhancement. Mass effect was evident in all lesions. Although not specific, when combined with the history and neurologic signs, MR features aid presumptive diagnosis that should be confirmed by cytology or histopathology.