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1.
Dose intense CHOP protocols have been shown to improve outcome for people with non‐Hodgkin's lymphoma, but evaluation of dose intense CHOP protocols for canine lymphoma is currently limited. The hypothesis of this retrospective study was that a 15‐week dose intense CHOP protocol would have shorter treatment duration with similar efficacy to other doxorubicin‐based multidrug protocols. Thirty‐one client owned dogs with multicentric lymphoma were treated with a 15‐week CHOP chemotherapy protocol with an overall response rate of 100% and a median progression‐free interval (PFI) of 140 days [95% confidence interval (CI) 91–335 days]. Dogs that had two or more treatment delays had significantly prolonged PFI and overall survival in multivariate analysis. Dose intensity did not correlate with patient outcome. Dogs experiencing multiple treatment delays secondary to adverse events may receive their individual maximally tolerated dose while dogs with no adverse events may be underdosed. Future studies should focus on individual patient dose optimization.  相似文献   

2.
Canine B‐cell lymphoma is a clinically heterogenous disease; however, it is generally treated as a single disease entity. The purpose of this clinical trial was to prospectively evaluate naïve canine B‐cell lymphoma patients using histopathology, flow cytometry (FC) and a standardized chemotherapy protocol to better define subsets of this disease that may respond differently to treatment. Sixty‐four dogs with naïve multicentric B‐cell lymphoma were treated with a standardized 19‐week CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy protocol. Most of the dogs (84.3%) were diagnosed with diffuse large B‐cell lymphoma (DLBCL), followed by nodal marginal zone (7.8%), small B‐cell (4.7%), Burkitt‐like (1.6%) and follicular lymphoma (1.6%). FC confirmed the diagnosis of B‐cell lymphoma in all cases. There were no clear phenotyping differences between the subtypes of B‐cell lymphoma detectable by our FC panel. The histologic subtypes in this study exhibited a range of forward scatter values on flow cytometry, but all of the DLBCL cases were higher than a value of 469, while the only cases with a lower forward scatter value were follicular lymphoma and diffuse small B‐cell lymphoma. Dogs with DLBCL had a significantly better objective response rate to the CHOP protocol (96.3%) than the non‐DLBCL subtypes (70%, P = .024). The median progression‐free survival time for patients with DLBCL (233 days) was significantly longer than that of all other histopathologic subgroups combined (163 days, P = .0005).  相似文献   

3.
A survey of canine lymphoma treatment strategies by veterinarians in first opinion practice was undertaken by sending questionnaires to 1000 randomly selected, first opinion small animal veterinary practices throughout England. Completed replies were received from 382 veterinarians. Ninety-five per cent of respondents had diagnosed canine lymphoma in the preceding 12 months. Eighty-seven per cent of respondents treated at least 50 per cent of the cases of canine lymphoma they diagnosed. A multidrug combination of vincristine, cyclophosphamide and prednisolone (COP) was the treatment protocol most commonly used. A doxorubicin-based treatment protocol was used by 2 per cent of respondents to treat canine lymphoma initially. The study suggests that, despite several reports of improved survival times with doxorubicin-based protocols, most veterinarians in first opinion practice in England treat canine lymphoma with COP.  相似文献   

4.
In humans B‐symptoms refer to systemic symptoms of lymphoma such as fever, weight loss, and night sweats and influence the prognosis of patients. In canine lymphoma, substage B is used to describe any clinical sign observed. Aim of the retrospective study was to compare the prognostic value of substage B with B‐symptoms to predict treatment response and survival in canine nodal diffuse large B‐cell lymphoma. Affected dogs treated with CHOP chemotherapy between 2008 and 2019 were included. B‐symptoms were defined by weight loss greater than 10% of normal weight, fever and the occurrence of unexplained resting tachypnoea substituted human night sweats. Substage B was defined as any symptoms but lymphadenopathy. Fifty‐five cases were included. B‐symptoms were present in 20/55 (36%) and substage B in 40/55 (74%) patients. No significant associations between B‐symptoms or substage B and weight, sex, breed, WHO stage and lymphoma grade were found. Treatment response was negatively associated with both substage B (P = .02) and B‐symptoms (P = .001). B‐symptoms significantly decreased progression free survival (PFS) (95 vs 330 days, P = .001) and lymphoma specific survival (LSS) (160 vs 462 days, P = .001). Data showed that B‐symptoms might be a more reliable prognostic indicator than substage B in canine nodal diffuse large B‐cell lymphoma. Prospective studies assessing B‐symptoms in a larger cohort of patients and in other common lymphoma types are warranted. The abstract was presented at the fourth meeting of the European Canine Lymphoma Network Group in Lugano, 22 June 2019 and published in the proceeding of the meeting on the page 26.  相似文献   

5.
Diagnostic methods used in the initial and post‐treatment evaluation of canine lymphoma are heterogeneous and can vary within countries and institutions. Accurate reporting of clinical stage and response assessment is crucial in determining the treatment efficacy and predicting prognosis. This study comprises a systematic review of all available canine multicentric lymphoma studies published over 15 years. Data concerning diagnosis, clinical stage evaluation and response assessment procedures were extracted and compared. Sixty‐three studies met the eligibility criteria. Fifty‐five (87.3%) studies were non‐randomized prospective or retrospective studies. The survey results also expose variations in diagnostic criteria and treatment response assessment in canine multicentric lymphoma. Variations in staging procedures performed and recorded led to an unquantifiable heterogeneity among patients in and between studies, making it difficult to compare treatment efficacies. Awareness of this inconsistency of procedure and reporting may help in the design of future clinical trials.  相似文献   

6.
The aim of the study was to report the outcome of treatment of 97 dogs with lymphoma that received a multi‐agent chemotherapy protocol containing epirubicin as the primary anthracycline. Seventy‐five dogs received a 25‐week protocol with no maintenance phase whilst 22 dogs received a maintenance phase. Complete response rate was 96% and time to first relapse (TTR) and overall survival (OS) time for all dogs were 216 and 342 days, respectively. Dogs with T‐cell lymphoma and those classified as WHO substage b had significantly poorer OS times and TTR. The protocol was well tolerated with toxicity similar to doxorubicin‐containing protocols. Epirubicin as part of a multi‐agent protocol is safe and effective in the treatment of canine multicentric lymphoma. There is a high initial response rate and an overall median survival time that is similar to other published doxorubicin‐containing protocols.  相似文献   

7.
The objectives of this retrospective study of 100 dogs with intraocular lymphoma were to describe the histomorphologic and immunohistochemical features of canine intraocular lymphoma, determine the proportion of cases with presumed solitary ocular lymphoma (PSOL) compared to multicentric disease, and assess the clinical outcomes of these patients. Selected cases from Penn Vet Diagnostic Laboratory and Comparative Ocular Pathology Lab of Wisconsin (2004–2015) were evaluated and subtyped using the WHO classification system. Peripheral T‐cell lymphoma and diffuse large B‐cell lymphoma were the two most common subtypes. Questionnaires were distributed to the referring veterinarians and veterinary ophthalmologists inquiring about clinical signs at time of enucleation, staging, patient outcome, treatment, and disease progression. Cases were categorized as PSOL if only ocular involvement was noted at the time of diagnosis based on the clinical staging criteria. The majority of cases (61%) did not have systemic involvement at the time of diagnosis, and these cases did not progress postoperatively. Median survival time (MST) was significantly higher for the presumed solitary intraocular cases: 769 vs. 103 days, hazard ratio of 0.23 (95% CI: 0.077–0.68). The subtype of lymphoma did not affect survival time. The results of this study suggest two significant points of clinical interest: the majority of dogs (61%) presented without signs of systemic involvement of lymphoma at the time of enucleation, and dogs with only ocular involvement showed no disease progression postenucleation.  相似文献   

8.
Multi‐agent chemotherapy (vincristine, epirubicin and prednisolone) including either cyclophosphamide (CEOP) or lomustine (LEOP) was given as first‐line chemotherapy to treatment‐naïve canine lymphoma patients with measurable, high grade T‐cell lymphoma (HGTCL). All patients responded to either CEOP or LEOP. Toxicity was typical of multi‐agent chemotherapy protocols and 25% of dogs receiving lomustine exhibited mild‐to‐moderate ALT elevation and 29% grade 3 or 4 neutropenia. Median progression‐free survival (100 versus 269 days) and overall survival (155 versus 327 days) were significantly higher in patients receiving LEOP compared to CEOP. Overall survival was improved for patients receiving LEOP compared to those receiving CEOP followed by lomustine‐based rescue therapy. The results of this retrospective study support further evaluation of lomustine as part of first‐line, multi‐agent therapy for patients with HGTCL.  相似文献   

9.
Malignant lymphomas are one of the most common malignancies occurring in dogs; among them T‐cell tumours are less commonly recognized. Recently, many authors have recommended cytology as a sufficient diagnostic method for canine lymphomas, especially if supported by immunocytochemistry or flow cytometry. The aim of the study was to characterize animal‐dependent risk factors in canine T‐cell lymphomas (TCLs) in Poland, including specific cytological subtypes. Determination of the type and subtype of the tumour was made based on the updated Kiel cytological classification adopted for dogs as previously described. Two breeds turned out predisposed to TCL (dog de Bordeaux and Boxer) while no predisposition to B‐cell lymphoma could be evidenced. Dogs with low‐grade lymphoma were significantly older than those with high‐grade lymphoma.  相似文献   

10.
OSU‐2S is a FTY720 (Fingolimod) derivative that lacks immunosuppressive properties but exhibits strong anti‐tumour activity in several haematological and solid tumour models. We have recently shown OSU‐2S to mediate potent cytotoxicity in human mantle cell lymphoma cell lines and primary cells. We report here the pre‐clinical activity of OSU‐2S in spontaneous B‐cell lymphoma of dogs which shares many characteristics of human lymphoma. OSU‐2S mediated apoptosis in canine B‐cell lines and primary B‐cell lymphoma cells obtained from spontaneous lymphoma bearing dogs. OSU‐2S induced reactive oxygen species (ROS) in canine lymphoma cells and inhibition of ROS partially rescued OSU‐2S‐mediated cell death. These studies provide a rational basis for the use of spontaneous lymphoma in pet dogs as a preclinical large animal model for the development of OSU‐2S as small molecule for treating people and dogs with lymphoma.  相似文献   

11.
Canine lymphoma is a heterogeneous group of diseases and many previous studies have evaluated the response of a mixed population of lymphoma cases to one specific treatment protocol. The aim of this retrospective study was to describe the outcome and prognostic factors in 42 cases of multicentric centroblastic diffuse large B‐cell lymphoma treated with either a COP‐type (35%) or CHOP‐type (64%) induction chemotherapy. The objective response rate to induction therapy was 94%; entire dogs had a greater rate of complete vs partial remissions than neutered dogs (P = .017). Median progression‐free survival for the first remission (PFS1) was 182 days; absence of anaemia at diagnosis (P = .002) and pretreatment neutrophil:lymphocyte ratio (NLR) below 9.44 (P = .015) were independently predictive of longer PFS1. Fifty‐eight percent of dogs received rescue protocols with an objective response rate of 81%; 31% of dogs received further rescue protocols (up to a total of 5) and the median number of protocols administered were 2. Median overall survival (OS) was 322 days, the 1‐year survival rate was 38% and the 2‐year survival rate was 9%. Lymphocyte:monocyte ratio above 1.43 (P = .031), NLR below 11.44 (P = .009), the combination of induction and rescue therapy (P = .030) and the total number of doxorubicin doses used (P = .002) were independently predictive of longer OS. Use of a COP‐type protocol induction compared with CHOP did not undermine OS providing doxorubicin was used as rescue therapy.  相似文献   

12.
The DMAC protocol (dexamethasone, melphalan, actinomycin‐D, cytarabine) has been evaluated in American studies for the treatment of relapsed canine lymphoma, comparing similarly to other rescue protocols. The aim of this study was to evaluate efficacy and toxicity of DMAC, in a larger UK cohort of resistant canine lymphomas. Medical records of dogs with resistant non‐Hodgkin high‐grade lymphomas that received DMAC as a rescue protocol were reviewed from 2007 to 2017. Response, time from initiation to discontinuation (TTD) and toxicity (Veterinary Cooperative Oncology Group criteria) were assessed. One hundred dogs were included; 86 received CEOP (modified CHOP including epirubicin) as first‐line treatment. Thirty‐five dogs (35%) responded: 21 complete responders (CRs) and 14 partial responders (PRs). Responders had significantly longer TTD (P < 0.001) compared with non‐responders: 62 days (range 28‐952) for CR vs 32 days (range 20‐70) for PR. Six CR received more than six cycles of DMAC (range 7‐36 cycles) and experienced a longer TTD (median 508, range 126‐952 days). Thrombocytopenia occurred in 45% (24 grade 1‐2, 21 grade 3‐4) and neutropenia in 36% of cases (29 grade 1‐2, 7 grade 3‐4). Gastrointestinal toxicity occurred in 42% of dogs (40 grade 1‐2, 2 grade 3‐4). Owing to chemotherapy toxicity, treatment was discontinued in five, and hospitalization required in six cases. In this study, response to DMAC was lower and of generally shorter duration than previously reported. Toxicity was high, but infrequently led to hospitalization or discontinuation of treatment.  相似文献   

13.
Canine multi‐centric B‐cell lymphoma shares similarities with diffuse large B‐cell (Non‐Hodgkin's) lymphoma (NHL) in people. In people with NHL, lymphopenia at diagnosis and first relapse and neutrophil/lymphocyte ratio (N:L) > 3.5 are negative prognostic factors for survival. The objective of this study was to determine if lymphocyte concentration at diagnosis and first relapse and N:L were prognostic for survival in dogs with newly diagnosed multi‐centric lymphoma. Medical records of 77 dogs with multi‐centric lymphoma treated with a CHOP‐based chemotherapy protocol were retrospectively evaluated. Absolute lymphocyte concentration and N:L ratio at presentation of dogs pre‐treated with steroids was not significantly different from dogs who had not received steroids. On multivariate analysis, only immunophenotype remained significant for progression‐free survival (PFS), whereas no variables remained significant for ST. A prospective study of these haematologic variables is warranted to assess their true significance.  相似文献   

14.
Death‐associated protein kinase (DAPK) is a serine/threonine kinase and a tumour suppressor gene. Diffuse large B‐cell lymphomas with inactivated DAPK through hypermethylation of a CpG island is known to result in a biologically aggressive phenotype in humans. This retrospective study was carried out to analyse the prognostic significance of DAPK CpG island hypermethylation in canine lymphoma. We hypothesized that DAPK CpG island hypermethylation can be a negative prognostic indicator in dogs with nodal high‐grade B‐cell lymphoma. Forty‐seven dogs with high‐grade B‐cell lymphoma, according to the updated Kiel classification, were evaluated after being treated with a CHOP (vincristine, cyclophosphamide, doxorubicin and prednisolone)‐based chemotherapy protocol. The methylation status of the DAPK CpG island was examined by methylation‐specific PCR. Progression‐free survival (PFS) and overall survival (OS) were compared using the Kaplan‐Meier analysis and log‐rank test. The cox proportional hazard regression model was used to evaluate the effect of multiple variables. Hypermethylation of the DAPK CpG island was detected in 21 of the 47 dogs. The PFS and OS in dogs with the hypermethylation (median: 220 and 266 days, respectively) were significantly shorter than those of dogs without hypermethylation (median: 301 and 412 days, respectively) (PFS, P = .036; OS, P = .007). In the multivariate analysis, hypermethylation of the DAPK CpG island remained an independent prognostic factor in predicting shortened PFS (P = .047) and OS (P = .021) as well as clinical substage b. Overall, hypermethylation of the DAPK CpG island was a negative prognostic factor in canine high‐grade B‐cell lymphoma.  相似文献   

15.
Diffuse large B‐cell lymphoma (DLBCL) is the most common haematopoietic malignancy in dogs. Recently, MYC and BCL2 expression levels determined with immunohistochemistry (IHC) were found to be prognostic in people with DLBCL. We hypothesized that canine DLBCL can be similarly subdivided into prognostic subtypes based on expression of MYC and BCL2. Cases of canine DLBCL treated with CHOP chemotherapy were retrospectively collected and 43 dogs had available histologic tissue and complete clinical follow‐up. Median values of percent immunoreactive versus immunonegative cells were used to determine positive or negative expression status. Completion of CHOP was significantly associated with a positive outcome. Compared with human patients, our canine DLBCL patients had high IHC expression of both MYC and BCL2, and relative expression levels of one or both markers were not associated with clinical outcome.  相似文献   

16.
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17.
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18.
Ki67 can discriminate between high‐ and low‐grade canine lymphomas, but its prognostic role in specific subtypes of the neoplasm is unknown. We assessed the prognostic significance of Ki67% (percentage of Ki67‐positive cells), evaluated by flow cytometry, in 40 dogs with high‐grade B‐cell lymphoma, treated with a modified Wisconsin–Madison protocol (UW‐25). The following variables were investigated for association with lymphoma specific survival (LSS) and relapse free interval (RFI): Ki67%, breed, sex, age, stage, substage, complete remission (CR). By multivariate analysis, Ki67% (P = 0.009) and achievement of CR (P = 0.001) were independent prognostic factors for LSS. Dogs with intermediate Ki67% (20.1–40%) presented longer LSS and RFI (median = 866 and 428 days, respectively) than dogs with low (median = 42 days, P < 0.001; median = 159 days, P = 0.014) or high (median = 173 days, P = 0.038; median = 100 days, P = 0.126) values. Determination of Ki67 is a prognostic tool that improves the clinical usefulness of flow cytometric analysis in canine high‐grade B‐cell lymphoma.  相似文献   

19.
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20.
A dose‐intensified/dose‐dense chemotherapy protocol for canine lymphoma was designed and implemented at the Veterinary Hospital of the University of Pennsylvania. In this study, we describe the clinical characteristics, prognostic factors, efficacy and toxicity in 130 dogs treated with this protocol. The majority of the dogs had advanced stage disease (63.1% stage V) and sub‐stage b (58.5%). The median time to progression (TTP) and lymphoma‐specific survival were 219 and 323 days, respectively. These results are similar to previous less dose‐intense protocols. Sub‐stage was a significant negative prognostic factor for survival. The incidence of toxicity was high; 53.9 and 45% of the dogs needed dose reductions and treatment delays, respectively. Dogs that required dose reductions and treatment delays had significantly longer TTP and lymphoma‐specific survival times. These results suggest that dose density is important, but likely relative, and needs to be adjusted according to the individual patient's toxicity for optimal outcome.  相似文献   

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