Outcome following treatment of feline gastrointestinal mast cell tumours.

Prognosis of feline gastrointestinal mast cell tumours (FGIMCT), based on limited available literature, is described as guarded to poor, which may influence treatment recommendations and patient outcome. The purpose of this study is to describe the clinical findings, treatment response, and outcome of FGIMCT. Medical records of 31 cats diagnosed with and treated for FGIMCT were retrospectively reviewed. Data collected included signalment, method of diagnosis, tumour location (including metastatic sites), treatment type, cause of death and survival time. Mean age was 12.9 y. Diagnosis was made via cytology (n = 15), histopathology (n = 13) or both (n = 3). Metastatic sites included abdominal lymph node (n = 10), abdominal viscera (n = 4) and both (n = 2). Therapeutic approaches included chemotherapy alone (n = 15), surgery and chemotherapy (n = 7), glucocorticoid only (n = 6) and surgery and glucocorticoid (n = 3). Lomustine (n = 15) and chlorambucil (n = 12) were the most commonly used chemotherapy drugs. Overall median survival time was 531 d (95% confidence interval 334, 982). Gastrointestinal location, diagnosis of additional cancers, and treatment type did not significantly affect survival time. Cause of death was tumour-related or unknown (n = 12) and unrelated (n = 8) in the 20 cats dead at the time of analysis. The prognosis for cats with FGIMCT may be better than previously reported, with 26% of cats deceased from an unrelated cause. Surgical and medical treatments (including prednisolone alone) were both associated with prolonged survival times. Treatment other than prednisolone may not be necessary in some cats. Continued research into prognostic factors and most effective treatment strategies are needed.

Metabolism of autologous and homologous IgG in rheumatoid arthritis.

The metabolism of radioiodinated IgG was studied in 20 patients with rheumatoid arthritis and 11 normal controls using autologous IgG and homologous IgG pooled from normal donors. Fractional catabolic rates in the controls were 4.44% of the autologous- and 4.29% of the homologous-labeled protein per day. The corresponding rates in the rheumatoid patients were 9.67% of the autologous- and 8.64% of the homologous-labeled protein per day. Extravascular catabolism occurred only in the rheumatoid group and accounted essentially for the entire increased catabolism of IgG observed in these patients. 10 patients were especially hypercatabolic, with fractional catabolic rates for autologous IgG greater than 10%. Moreover, they catabolized their autologous IgG significantly faster than the homologous IgG (12.6 vs. 9.9%). The increment of catabolism of autologous over homologous IgG also occurred in the extravascular compartment. These highly hypercatabolic patients had a significantly increased number of manifestations of extra-articular disease. The hypercatabolism of IgG could not be correlated with age, weight, sex, duration of disease, joint erosions, corticosteroid therapy, erythrocyte sedimentation rate, rheumatoid factor titer, serum IgG concentration, or circulating immune complexes as measured by the Raji cell radioimmunoassay. Conceivable sites of extravascular catabolism and possible causes of faster catabolism of autologous (rheumatoid) than of homologous (normal) IgG are discussed.

Efficacy and toxicity of carboplatin and cytarabine chemotherapy for dogs with relapsed or refractory lymphoma (2000-2013).

Medical records of 22 dogs treated with carboplatin (n = 8) or carboplatin and cytarabine (n = 14) chemotherapy for relapsed or refractory lymphoma between 2000 and 2013 were retrospectively reviewed. The clinical response rate was 18.2% (4/22). Median time to progression was 18 days (56 for responders; 12 for non-responders, P = 0.0006). Median overall survival time was 28 days (109 for responders; 21 for non-responders, P = 0.0007). Thrombocytopenia and neutropenia occurred in 84.2% (16/19) and 52.6% (10/19), respectively. Grade IV thrombocytopenia and neutropenia occurred in 56.3% (9/16) and 60.0% (6/10), respectively. Dogs that received both drugs were more likely to become neutropenic (P = 0.022) or thrombocytopenic (P = 0.001) than dogs receiving carboplatin alone. All responders received both drugs giving a 28.6% (4/14) response rate for the combination. Although some dogs responded to the combination, toxicity was high and the responses were not durable. With adequate supportive care, this protocol may be an acceptable rescue option for some dogs.

Febrile neutropenia in cats treated with chemotherapy.

The purpose of this study was to describe the clinical presentation, potential causative agents, treatment and outcome of febrile neutropenia (FN) in chemotherapy-treated cats. Medical records from eight institutions were retrospectively reviewed. A total of 22 FN events in 20 cats were evaluated. Lymphoma was the most common cancer diagnosis; lomustine and vinca alkaloids were the most frequently implicated causative agents. Presenting clinical signs included decreased appetite, lethargy, vomiting and diarrhoea. Median body temperature and absolute neutrophil count at presentation were 104.1 °F; 40 °C (range: 103.1-105.1 °F; 39.5-40.6 °C) and 246 mL-1 (range: 0-1600 mL-1 ), respectively. Median number of days between chemotherapy administration and FN onset was 5 (range: 4-25 days). All but one cat were treated with intravenous fluids and broad spectrum antibiotics. Fevers resolved in all cases and absolute neutrophil counts returned to normal in 19 cats. Clinical presentation of cats with FN appears similar to that of dogs.

Evaluation of histological grade and histologically tumour-free margins as predictors of local recurrence in completely excised canine mast cell tumours.

Completeness of mast cell tumour (MCT) excision is determined by assessment of histologically tumour-free margins (HTFM). The HTFM width necessary to prevent local recurrence (LR), recognized as histologic safety margin (HSM) in human oncology, has not been defined. We hypothesized that HTFM width would correlate with risk for LR and high-grade tumours would require wider HTFM than low-grade tumours. Records of dogs with completely excised MCTs were included. Signalment, two-tier tumour grade, tumour size, HTFM width, recurrence and therapy data was collected. High-grade (n = 39) tumours were more likely to recur than low-grade (n = 51) tumours (35.9% versus 3.9%), P < 0.0001, with no association between HTFM width and LR. Twenty-nine percent of low-grade tumours had HTFM less than 3 mm; none recurred. Narrow (≤3 mm) histologic margins are likely adequate to prevent LR of low-grade tumours. High-grade tumours have significant risk of LR regardless of HTFM width.

Early tumor response to intraarterial or intravenous administration of carboplatin to treat naturally occurring lower urinary tract carcinoma in dogs.

BACKGROUND: Survival times and tumor responses associated with malignant neoplasia of the lower urinary tract are poor despite the vast array of current treatments. Therefore, the evaluation of alternative treatments, such as intraarterial administration of chemotherapy (IAC) should be considered. OBJECTIVE: To describe a technique for superselective catheterization for IAC and to evaluate initial tumor response by ultrasonography after both IAC and intravenous administration of chemotherapy (IVC). ANIMALS: Client-owned dogs with lower urinary tract neoplasia treated with either IVC (n = 15) or IAC (n = 11). METHODS: Retrospective study. An arterial approach via the carotid or femoral artery was utilized to obtain superselective access and administer chemotherapy in the IAC cases. Medical record review was performed, data were recorded, and recorded variables were evaluated statistically. RESULTS: Intraarterial chemotherapy was successfully administered in all cases. There was a significantly greater decrease in longest unidimensional measurement in the IAC group as compared to the IVC group (P = .013). The IAC group was also significantly more likely to have a tumor response as assessed by modified RECIST guidelines (P = .049). Dogs in the IAC group were significantly less likely to develop anemia (P = .001), lethargy (P = .010) and anorexia (P = .024). CONCLUSION AND CLINICAL IMPORTANCE: This study demonstrated the feasibility and efficacy of performing IAC for lower urinary tract neoplasia. Further investigation is necessary as the follow-up time was short and the impact on long-term outcome and survival was not determined.

Prospective clinical trial to compare vincristine and vinblastine in a COP-based protocol for lymphoma in cats.

BACKGROUND: Current standard chemotherapy protocols for lymphoma in cats carry risks of gastrointestinal toxicity, which can decrease quality of life and complicate response assessment. Protocols with less gastrointestinal toxicity may improve treatment tolerance. HYPOTHESIS/OBJECTIVES: The study purpose was to compare response rate, outcome, and toxicity between cats that received vincristine or vinblastine as part of combination chemotherapy for lymphoma. We hypothesized that vinblastine would have similar efficacy, but less gastrointestinal toxicity, compared with vincristine. ANIMALS: Forty client-owned cats with confirmed diagnosis of lymphoma. METHODS: Cats were randomized to 1 of 2 treatment arms and received weekly COP-based chemotherapy for 6 months or until disease progression. Response rate, progression-free survival (PFS), lymphoma-specific survival (LSS), and incidence and severity of gastrointestinal and hematologic toxicity were compared between arms. Arm cross-over occurred if specific gastrointestinal toxicity criteria were noted. RESULTS: Cats in both arms had similar response rates, PFS, and LSS (48 versus 64 days, P = .87; 139 versus 136 days, P = .96). Cats that received vincristine were significantly more likely to switch arms based on gastrointestinal toxicity than cats that received vinblastine (44.4 versus 10.5%, P = .02). Lower baseline weight was significantly negatively associated with PFS and LSS (P = .01, P = .003, respectively). Baseline anemia was significantly negatively associated with LSS (P = .04). CONCLUSIONS AND CLINICAL IMPORTANCE: Results suggest that vinblastine is a reasonable alternative to vincristine in the treatment of some cats with lymphoma. Baseline body weight remains a significant prognostic factor for cats with lymphoma.

Preliminary evidence for biologic activity of toceranib phosphate (Palladia(®)) in solid tumours.

The purpose of this study was to provide an initial assessment of the potential biologic activity of toceranib phosphate (Palladia®, Pfizer Animal Health, Madison, NJ, USA) in select solid tumours in dogs. Cases in which toceranib was used to treat dogs with apocrine gland anal sac adenocarcinoma (AGASACA), metastatic osteosarcoma (OSA), thyroid carcinoma, head and neck carcinoma and nasal carcinoma were included. Clinical benefit (CB) was observed in 63/85 (74%) dogs including 28/32 AGASACA [8 partial response (PR), 20 stable disease (SD)], 11/23 OSAs (1 PR and 10 SD), 12/15 thyroid carcinomas (4 PR and 8 SD), 7/8 head and neck carcinomas [1 complete response (CR), 5 PR and 1 SD] and 5/7 (1 CR and 4 SD) nasal carcinomas. For dogs experiencing CB, the median dose of toceranib was 2.8 mg kg(-1) , 36/63 (58.7%) were dosed on a Monday/Wednesday/Friday basis and 47/63 (74.6%) were treated 4 months or longer. Although these data provide preliminary evidence that toceranib exhibits CB in dogs with certain solid tumours, future prospective studies are necessary to define its true activity.

Outcome and toxicity associated with a dose-intensified, maintenance-free CHOP-based chemotherapy protocol in canine lymphoma: 130 cases.

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.

Cytological lymph node evaluation in dogs with mast cell tumours: association with grade and survival.

The purpose of this retrospective cohort study is to describe the association of cytological assessment of lymph node metastasis with survival and tumour grade in dogs with mast cell tumours. Regional lymph node aspirates of 152 dogs diagnosed with a mast cell tumour were reviewed and classified according to specific cytological criteria for staging. 97 dogs (63.8%) had stage I tumours, and 55 (36.2%) had stage II tumours. Stage II dogs had a significantly shorter survival time than dogs with stage I disease (0.8 and 6.2 years, respectively; P < 0.0001). Dogs with grade III mast cell tumours were more likely to have stage II disease (P = 0.004). These results suggest that cytological evaluation of lymph nodes in dogs with mast cell tumours provides useful and valuable clinical information, and the results correlate with tumour grade and outcome thus providing a practical and non-invasive method for staging.

Long-term survival in dogs with localized histiocytic sarcoma treated with CCNU as an adjuvant to local therapy.

Histiocytic sarcoma (HS) is associated with a poor prognosis owing to the presence of metastasis at the time of diagnosis in most dogs. Improved outcome has been reported in several dogs with localized HS following local therapy, however, distant metastasis occurs in 70-91% of dogs suggesting that adjuvant systemic therapy is necessary. The purpose of this retrospective study was to describe clinical characteristics and outcome in dogs with localized HS treated with aggressive local therapy plus adjuvant CCNU chemotherapy. Data from 16 dogs were evaluated. The median disease-free interval was 243 days. Two dogs had local recurrence and eight dogs developed metastatic disease with a median time to relapse of 201 days in these 10 dogs. The median survival time for all 16 dogs was 568 days. These results support the recommendation for aggressive local therapy combined with adjuvant CCNU chemotherapy in dogs with localized HS.

Description of clinical and pathological findings, treatment and outcome of feline large granular lymphocyte lymphoma (1996-2004).

Feline large granular lymphocyte (LGL) lymphoma is an uncommon, morphologically distinct variant of feline lymphoma. Limited information exists in the literature regarding pathological and immunohistochemical descriptions, clinical findings, treatment and survival times. The purpose of this study was to describe clinical features, treatment and outcome in feline LGL lymphoma. Medical records of 45 cats with LGL lymphoma were retrospectively evaluated. Decreased appetite/anorexia, weight loss, lethargy and vomiting were the most commonly reported clinical signs. All cats tested for feline leukaemia virus and feline immunodeficiency virus infection were negative. The mesenteric lymph nodes and small intestine were the most commonly affected organs. One complete response and six partial responses were noted in the 23 cats that received chemotherapy as their initial treatment. Median survival time for cats that were treated was 57 days. Based on these results, feline LGL lymphoma appears to be minimally responsive to chemotherapy and is associated with a grave prognosis.

Metabolism of factor B of serum complement in rheumatoid arthritis.

An increased rate of catabolism of radio-iodinated Factor B has been shown in five out of ten patients with rheumatoid arthritis. Serum levels of Factor B were normal, the increased catabolism being matched by increased synthesis. The patients showing high catabolic rates had more manifestations of extra articular disease than did those with normal catabolic rates and they had higher rheumatoid factor titres. In seven patients, the catabolic rate for Factor B correlated significantly with the rate of IgG catabolism. In this series, the Raji-cell assay for immune complex-like material was in the normal or near normal range in all but one patient.

Hodgkin's lymphoma in a patient treated for Wegener's granulomatosis with cyclophosphamide and azathioprine.

Only 5 neoplasms have been reported associated with the use of cytotoxic drugs in the treatment of Wegener's granulomatosis. Described here for the first time, to our knowledge, is a patient with Wegener's granulomatosis treated with cyclophosphamide and azathioprine who later developed Hodgkin's lymphoma.