Evaluation of ifosfamide for treatment of various canine neoplasms

lfosfamide (3-[2-chloroethyl]-2[(2 chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide) is an alkylating agent with a broad spectrum of antitumor activity. The efficacy and toxicity of ifosfamide were evaluated in 72 dogs with spontaneously occurring tumors. Forty dogs (56%) had lymphoma, 31 (43%) had sarcomas, and 1 had a metastatic carcinoma. Five dogs received ifosfamide at dosages <350 mg/m2 IV. Neither toxicity nor response were observed, and the remaining dogs received ifosfamide at 350 mg/m2 (n = 18) and 375 mg/m2 body surface area IV (n = 49). Saline diuresis and the thiol compound mesna were used to prevent urothelial toxicity. Fifty-two dogs had measurable tumors and could be evaluated for response. Complete responses were seen in 1 dog with metastatic leiomyosarcoma of the urinary bladder and in 1 dog with metastatic cutaneous hemangiosarcoma. One dog with lymphoma had a partial response for 112 days. Six dogs with splenic hemangiosarcoma received ifosfamide postsplenectomy and their median survival time was 147 days. The acute dose limiting toxicity was neutropenia 7 days after administration of ifosfamide. The median and mean neutrophil counts 7 days after ifosfamide at 350 mg/m2 were 2,035 cells/microL and 4,773 cells/microL, respectively (n = 12). The median and mean neutrophil counts 7 days after ifosfamide at 375 mg/m2 were 2,500 cells/microL and 3,594 cells/microL, respectively (n = 37). No dog developed clinical or microscopic evidence of hemorrhagic cystitis. Ifosfamide appears safe to use in tumor-bearing dogs, and the evaluation of combination chemotherapy protocols that include ifosfamide should be considered.     

Treatment of canine mast cell tumors with CCNU (lomustine)

The efficacy and toxicity of CCNU (1-[2-chloroethyl]3-cyclohexyl-1-nitrosourea) were evaluated in 23 dogs with measurable mast cell tumors (MCT). Twenty-two dogs had cutaneous MCT and 1 dog had an intranasal MCT Nineteen (83%) dogs had biopsy of their original mass performed and 4 (17%) had aspiration cytology of masses. Of the 19 tumors histologically graded, 1 (5%) neoplasm was classified as grade I, 10 (53%) were grade II, and the remaining 8 (42%) were grade III. Dogs were treated with CCNU at a dosage of 90 mg/m2 body surface area every 3 weeks. Response could be evaluated in 19 dogs. Eight of the 19 dogs (42%) had a measurable response to CCNU. One dog had a durable complete response for 440 days. Seven dogs (37%) had a partial response for a median and mean duration of 77 days and 109 days, respectively (range, 21-254 days). Treatment with CCNU resulted in stable disease in 6 dogs (32%) for a median and mean duration of 78 days and 122 days, respectively (range, 42-347 days). The acute dose-limiting toxicity was neutropenia 7 days after administration of CCNU. The median and mean neutrophil counts 7 days after CCNU were 1,452 cells/microL and 1,683 cells/microL, respectively (n = 17). Other toxicoses were uncommon. CCNU should be considered an active agent in the treatment of MCT in dogs.     

Treatment and Long-Term Follow-up of 205 Dogs With Hypoadrenocorticism

Results of long-term treatment were evaluated in 200 dogs with primary hypoadrenocorticism and 5 dogs with spontaneous secondary hypoadrenocorticism. Fludrocortisone acetate initially was used for mineralocorticoid replacement in 190 of the dogs with primary hypoadrenocorticism. The daily dose of fludrocortisone required in these dogs increased significantly during the treatment period (median, 2.6 years) from an initial median dose of 13.1 μg/kg to a final dose of 22.6 μg/kg. In 27 of the 200 dogs, mineralocorticoid therapy was changed from fludrocortisone to desoxycorticosterone pivalate (DOCP) because of adverse effects, poor response, or financial considerations. The dose of DOCP required in the 33 dogs (27 dogs plus 6 dogs initially given DOCP) increased significantly during the treatment period (median, 3.5 years) from an initial median dose of 1.56 mg/kg to a final dose of 1.69 mg/kg; the interval between DOCP injections ranged from 14 to 35 days (median, 30 days). The dose of prednisone administered to the dogs with primary hypoadrenocorticism decreased significantly from an initial median dose of 0.3 mg/kg to a final dose of 0.2 mg/kg; the drug was discontinued in 22 dogs due to adverse effects. The 5 dogs with secondary hypoadrenocorticism received only glucocorticoid replacement therapy (prednisone) at initial and final daily dosages of 0.41 mg/kg and 0.25 mg/kg, respectively, during a median treatment period of 4.4 years. More than 80% of the dogs were considered to have a good to excellent response to therapy. The median survival time of all 205 dogs was 4.7 years. There were no differences in response to treatment or survival between dogs treated with fludrocortisone and those receiving DOCP, or between dogs with primary hypoadrenocorticism and those with secondary hypoadrenocorticism.     

Histiocytic sarcomas in flat-coated retrievers: a summary of 37 cases (November 1998–March 2005)

Thirty‐seven cases of histiocytic‐like sarcomas (HLSs) in flat‐coated retriever dogs were evaluated retrospectively. This tumour accounted for 36% of the malignant tumours seen in this breed during the study period. The median age at presentation was 8.2 years. Thirty‐four dogs presented with a swelling or mass in a muscle group or surrounding a joint. The remaining three presented for rib (1), cutaneous (1) or primary splenic origin (1). A high rate of metastasis to local lymph nodes (45%), thorax (20%) and abdominal organs (20% confirmed) was seen. Overall metastastic rate by the time of death was 70%. The median survival for all dogs was 123 days. The most significant prognostic indicator was presence of distant metastasis at the time of diagnosis with median survival of 68 or 200 days, with or without metastasis, respectively. Chemotherapy and radiation therapy significantly improved survival. Dogs given chemotherapy survived a median of 185 versus 34 days for dogs that were not (P = 0.0008). Dogs treated with radiation survived a median of 182 versus 60 days for those that were not (P = 0.0282). Dogs receiving only palliative therapy survived a median of 17 versus 167 days in dogs receiving any kind of radiation, chemotherapy, surgery or combinations. A set protocol of radiation and CCNU (RTCCNU) induced minimal toxicity and provided a median survival of 208 versus 68 days for all other dogs. While this tumour carries a poor long‐term prognosis in flat‐coated retrievers, it is reasonable to treat these dogs for palliation of signs and extension of life.     

Prognostic factors for mortality and thromboembolism in canine immune-mediated hemolytic anemia: a retrospective study of 72 dogs

Medical records of 72 dogs diagnosed with immune-mediated hemolytic anemia (IMHA) were reviewed to find risk factors for the disease, for mortality, and for thromboembolism. Coagulation data of 32 patients were evaluated for mortality or thromboembolism risk factors. Cocker Spaniels were at increased risk for IMHA (P = .012). Timing of vaccination was not associated with development of IMHA. PCV ranged from 5 to 33%, with a mean of 16 +/- 5%. Autoagglutination was present in 42% of the dogs. Platelet counts (n = 60) varied from 3,000 to 793,000/microL (mean, 160,117 +/- 133,571; median, 144,000). Thrombocytopenia (platelet count, <200,000/microL) was present in 70% of the dogs, with severe thrombocytopenia (platelet count, <50,000/microL) being present in 22%. One-step prothrombin time (OSPT) was prolonged in 28% of the dogs tested, and activated partial thromboplastin time (APTT) was prolonged in 47% of the dogs tested. Fibrin(ogen) degradation products (FDPs) were detected in 16 of 28 dogs tested (57%). Disseminated intravascular coagulation (DIC) was diagnosed in 10 of 31 (32%) dogs and was suspected in 8 dogs. Thromboemboli were found in 20 of 25 dogs given postmortem examinations. Mortality rate was 58%. Thrombocytopenia (P = .008) and serum bilirubin concentration of >5 mg/dL (P = .015) were risk factors for mortality, and hypoalbuminemia approached significance (P = .053). Severe thrombocytopenia (P = .046), serum bilirubin concentration of >5 mg/dL (P = .038), and hypoalbuminemia (P = .016) were risk factors for thromboembolism. On evaluation of continuous data, decreased platelet count (P = .057), increased bilirubin (P = .062), and decreased albumin (P = .054) approached significance for decreased survival. A higher risk for thrombosis was found with increased alkaline phosphatase (ALKP) (P = .042), increased bilirubin (P = .047), and decreased albumin (P = .012).     

Characteristics of cisternal cerebrospinal fluid associated with intracranial meningiomas in dogs: 56 cases (1985-2004)

OBJECTIVE: To determine CSF characteristics associated with intracranial meningiomas in dogs. DESIGN: Retrospective case series. ANIMALS: 56 dogs with intracranial meningiomas. PROCEDURES: Medical records of dogs with a histopathologic diagnosis of intracranial meningioma, in which CSF analysis had been performed, were reviewed. Information concerning total nucleated cell counts (TNCCs) and differential nucleated cell counts, RBC counts, and total protein concentration in CSF; seizure history and glucocorticoid administration; and location of meningiomas was recorded. RESULTS: TNCCs < 5 cells/microL were detected in 41 of 56 (73%) dogs; 5 of 56 (9%) dogs had TNCCs > 50 cells/microL. Analysis of CSF revealed predominantly neutrophilic pleocytosis in < 20% of dogs. There was a significant association between meningioma location (caudal portion of the cranial fossa or middle and rostral portion of the cranial fossae) and increased TNCCs (> or = 5 cells/microL). CONCLUSIONS AND CLINICAL RELEVANCE: Results were significantly different from those routinely reported in the veterinary literature. Neutrophilic pleocytosis, especially with TNCCs > 50 cells/microL, was not typical in CSF samples from dogs with intracranial meningiomas. Neutrophilic pleocytosis may not be detected in CSF samples from dogs with meningiomas located within the middle or rostral portion of the cranial fossae.     

Leiomyosarcoma in dogs: 44 cases (1983-1988).

During a 5-year period, leiomyosarcoma was diagnosed in 57 dogs. Forty-four dogs were included in the study on the basis of completeness of medical records. All dogs underwent exploratory laparotomy, and dogs were allotted to 4 groups according to primary site of tumor: spleen (16 dogs, median age 10.3 years), stomach/small intestine (13 dogs, median age 10.3 years), cecum (10 dogs, median age 11.8 years), and liver (5 dogs, median age 9 years). All dogs with leiomyosarcoma of the liver had visible metastasis and were euthanatized at surgery. In the other 3 groups, 79% of the dogs had no gross evidence of metastasis at surgery, and 64% survived greater than 2 weeks. Median survival in these 3 groups was 10 months (range, 1 month to 7 years); 48% died of metastasis, 32% died of unrelated causes, and 16% died of unknown causes. The prognosis in dogs with leiomyosarcoma of the spleen, stomach, small intestine, and especially the cecum is good to excellent if surgery is performed. In dogs with leiomyosarcoma of the liver, the prognosis is poor.     

Evaluation of survival times after limb amputation, with and without subsequent administration of cisplatin, for treatment of appendicular osteosarcoma in dogs: 30 cases (1979-1990).

Appendicular osteosarcoma was diagnosed in 30 dogs. Fifteen dogs were treated by limb amputation alone, and 15 dogs were treated by limb amputation followed by 2 doses of cisplatin given IV approximately 2 and 7 weeks after limb removal. Mean survival time after limb amputation alone +/- SD was 190 +/- 138 days (median, 168 days); 7 dogs survived longer than 6 months, and 3 dogs survived more than 1 year. Fourteen of 15 dogs treated by amputation and administration of cisplatin survived a mean of 315 +/- 158 days (median, 290 days) after amputation, and 1 dog was still alive at 1,095 days; 13 dogs survived longer than 6 months and 5 dogs survived more than 1 year. Survival time was significantly (P less than 0.05) greater in dogs given cisplatin.     

Treatment of severe immune-mediated thrombocytopenia with human IV immunoglobulin in 5 dogs

BACKGROUND: Glucocorticoids with or without other immunotherapy are the initial treatment of choice for dogs with severe immune-mediated thrombocytopenia (IMT). The majority of treated dogs will have improvements in platelet counts within 5 to 7 days of starting therapy, but complications from hemorrhage often occur before a response is seen. Human IV immunoglobulin (hIVIG) blocks Fc receptors on mononuclear phagocytic cells in dogs; it is used in people with idiopathic thrombocytopenic purpura. HYPOTHESIS: The purpose of this study was to describe adverse effects and benefit of hIVIG in addition to conventional immunosuppressive therapy in dogs with severe IMT. ANIMALS: Five client-owned dogs with severe primary IMT. METHODS: Case series. The hospital database was searched for dogs with primary IMT treated with hIVIG. RESULTS: No adverse effects were noted during or after hIVIG infusion in any treated dog. Over a 6-month follow-up, all dogs were clinically normal when using conventional immunosuppressive therapy. Human IVIG was administered 3 days after initiation of immunosuppressive therapy in 4 dogs, and, after 2 days, in 1 dog. In all dogs, the mean platelet counts pre- and 24 hours post-hIVIG infusion (0.28-0.76 g/kg) were 2,500/pL and 50,600/microL (62,750/microL for the 4 responders), respectively. One dog failed to respond as promptly to hIVIG (0.34 g/kg), and the platelet count increased to 66,000/microL after 9 days of immunosuppressive therapy. The mean duration of hospitalization post-hIVIG in all 5 dogs was 1.8 days (12 hours for responders), and the mean total length of hospitalization was 4.6 days (3.5 days for responders). Active hemorrhage resolved and no packed red blood cell transfusions were required after hIVIG infusion for responders. CONCLUSIONS AND CLINICAL IMPORTANCE: Human IVIG was well tolerated and appeared to be associated with rapid platelet count recovery and amelioration of clinical signs in most dogs with IMT.     

Neutropenia associated with vincristine and L-asparaginase induction chemotherapy for canine lymphoma

Vincristine (VCR) and L-asparaginase (L-ASP) are commonly used to treat canine lymphoma. As single agents, these drugs are not myelosuppressive. However, in combination, VCR and L-ASP cause severe neutropenia in some dogs. It has been recommended that L-ASP be administered 12-24 hours after VCR to minimize toxicity. The purpose of this retrospective study was to determine the prevalence of neutropenia after VCR/L-ASP induction therapy for canine lymphoma and to evaluate risk factors for myelosuppression, especially the interval between VCR and L-ASP administration. Medical records of 147 dogs were reviewed. L-ASP was given 0 (n = 50), 6 (n = 23), 18 (n = 20), or 24 (n = 54) hours after VCR. Forty percent of the dogs were neutropenic 7 days after VCR/L-ASP, and 18% had neutrophil counts of <1,000 cells/microL. The median neutrophil count was 3,712 cells/microL (range 0-30,968 cells/microL). No correlation was found between administration interval and day 7 neutrophil count (P = .84) or development of gastrointestinal signs, including vomiting (P = .80), diarrhea (P = .52), and decreased appetite (P = .30). No significant predictors of neutropenia were identified. Higher clinical stage and substage b were associated with decreased appetite after treatment (P = .04 and .01, respectively). Sixteen percent of the dogs were hospitalized. This study demonstrates that VCR/L-ASP induction for canine lymphoma may result in neutropenia but that separation of VCR and L-ASP administration may not be necessary to avoid toxicity.     

Serum Levels of 25-Hydroxycholecalciferol and 1,25-Dihydroxycholecalciferol in Dogs with Hypercalcaemia

1,25-Dihydroxycholecalciferol (1,25-(OH)2-D3) and 25-hydroxycholecalciferol (25-OH-D3) were measured among dogs with hypercalcaemia (total serum calcium > 3.01 mmol/L) due to various causes. All values were compared to those of healthy control dogs. Serum 1,25-(OH)]2-D3 was measured by a radioimmunoassay test and serum 25-OH-D3 was measured by a protein binding assay. 1,25-(OH)2-D3 ranged from 26 to 332 pmol/L (median 110.0) in dogs with lymphoma (n = 12); from 61 to 398 pmol/L (median 248.0) in dogs with primary hyperparathyreoidism (n = 5); from 28 to 310 pmol/L (median 88.5) in dogs with chronic renal failure (n = 10); and from 60 to 239 pmol/L (median 157.5) in control dogs (n = 24). There was no significant difference in 1,25-(OH)2-D3 among dogs with different causes of hypercalcaemia. 25-OH-D3 ranged from 64 to 291 nmol/L (median 101.5) in dogs with lymphoma; from 66 to 298 nmol/L (median 91.0) in dogs with primary hyperparathyreoidism; from 35 to 184 nmol/L (median 67.0) in dogs with chronic renal failure; and from 48 to 350 nmol/L (median 306.5) in control dogs. 25-OH-D3 was significantly lower in dogs with lymphoma, primary hyperparathyroidism and chronic renal failure than in control dogs. 1,25-(OH)2-D3 and 25-OH-D3 are not predictable in dogs with hypercalcaemia.     

Idiopathic lymphoplasmacytic rhinitis in dogs: 37 cases (1997-2002)

OBJECTIVE: To determine clinical signs and rhinoscopic, computed tomographic, and histologic abnormalities in dogs with idiopathic lymphoplasmacytic rhinitis. DESIGN: Retrospective case series. ANIMALS: 37 dogs. PROCEDURE: Clinical information was obtained from medical records. Nasal computed tomographic images and histologic slides of biopsy specimens were reviewed. RESULTS: Dogs ranged from 1.5 to 14 years old (mean, 8 years); most (28) were large-breed dogs. Nasal discharge was unilateral in 11 of 26 (42%) dogs and bilateral in 15 of 26 (58%) dogs. In dogs with unilateral disease, duration of clinical signs ranged from 1.5 to 36 months (mean, 8.25 months; median, 2 months), and in dogs with bilateral disease, duration of signs ranged from 1.25 to 30 months (mean, 6.5 months; median, 4 months). Computed tomography (n = 33) most often revealed fluid accumulation (27/33 [82%]), turbinate destruction (23/33 [70%]), and frontal sinus opacification (14/33 [42%]). Rhinoscopy (n = 37) commonly demonstrated increased mucus and epithelial inflammation; turbinate destruction was detected in 8 of 37 (22%) dogs. Bilateral biopsy specimens from all 37 dogs were examined. Four dogs had only unilateral inflammatory changes. The remaining 33 dogs had bilateral lesions; in 20, lesions were more severe on 1 side than the other. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggest that idiopathic lymphoplasmacytic rhinitis is a key contributor to chronic nasal disease in dogs and may be more common than previously believed. In addition, findings suggest that idiopathic lymphoplasmacytic rhinitis is most often a bilateral disease, even among dogs with unilateral nasal discharge.     

Serum Erythropoietin Concentrations Measured by Radioimmunoassay in Normal, Polycythemic, and Anemic Dogs and Cats

Serum erythropoietin (Epo) concentrations were measured by radioimmunoassay (RIA) in normal, polycythemic, and anemic dogs and cats. The serum Epo concentration in normal dogs ( n = 25) ranged from 7 to 37 mU/mL (median, 20 mU/mL); and in normal cats ( n = 11) ranged from 9 to 38 mU/mL (median, 18 mU/mL). Polycythemic animals (PCV < 55% in dogs, > 45% in cats) were classified as those with primary (polycythemia vera), secondary, or polycythemia of uncertain etiology. Dogs with polycythemia vera (PV, n = 8) had a median serum Epo concentration in the normal range (17 mU/mL); cats with PV ( n = 7) also had a median serum Epo concentration that was within the normal range (10 mU/mL). In the category of secondary polycythemias, dogs ( n = 7) (median, 30.7 mU/mL) and cats ( n = 2) had normal Epo concentrations. The median serum Epoconcentration was significantly decreased ( P > .05) in dogs with PV compared with dogs with secondary polycythemias. The median serum Epo concentrations in dogs ( n = 13) and cats ( n = 5) with anemias not due to chronic renal disease were significantly increased ( P > .05) compared with normal dogs and cats. In cats with anemias due to chronic renal disease ( n = 5) the median serum Epo concentration was not significantly different from normal cats. The measurement of the serum EPO concentration may be useful in assessment of anemia or polycythemia but the overlap of values with the normal range in all groups evaluated limit its diagnostic use.     

OSTEORADIONECROSIS AND RADIATION INDUCED BONE TUMORS FOLLOWING ORTHOVOLTAGE RADIATION THERAPY IN DOGS

Osteoradionecrosis and radiation-induced bone tumors are rare complications of radiation therapy. Little information regarding these complications is available in veterinary medicine. We characterized these complications and investigated risk factors in 119 dogs (122 sites) that received definitive orthovoltage radiation therapy to appendicular sites. Long-term survival was expected in all dogs. The complications of interest were osteoradionecrosis and secondary bone tumor, evaluated radiographically, histopathologically, or both. Complication rates were estimated using the Kaplan–Meier product-limit method, and Fisher's exact test or chi-square test was used to compare the complication rate. The median survival time was 1405 days, with median follow-up duration of 657 days. There were 10 radiation-induced bone tumors and five radiation-induced fractures, with two dogs developing both, for an overall complication rate of 11%. The latent period ranged from 1.2 to 6.4 years for osteoradionecrosis and from 2.6 to 8.7 years for radiation-induced bone tumor. Complications were significantly higher in the humerus ( P <0.0001), and in dogs younger than 7 years ( P =0.014). Similar assessment of complications in dogs irradiated with megavoltage photons or electrons are needed.     

Surgical decompression,with or without adjunctive therapy,for palliative treatment of primary vertebral osteosarcoma in dogs

Vertebral osteosarcoma (OSA) is the most common primary vertebral tumor in dogs, however studies examining the survival time after surgical decompression of these tumors are limited. There is also limited information regarding the benefit of adjunctive treatments such as radiation therapy or chemotherapy in these patients. The goal of this study was to determine survival time of dogs with primary vertebral OSA after palliative decompressive surgery alone and combined with radiation therapy and/or chemotherapy. Records from 22 client‐owned dogs diagnosed with primary vertebral OSA and treated with decompressive surgery were collected retrospectively from eight referral institutions. Survival time was assessed for dogs treated with surgery alone as well as dogs who received adjunctive radiation therapy and/or chemotherapy. Median survival time in the 12 dogs treated with surgery alone was 42 days (range: 3‐1333 days). The three dogs treated with surgery and chemotherapy had a median survival time of 82 days (range: 56‐305 days). Only one dog was treated with surgery and radiation therapy; this dog survived 101 days. Six dogs were treated with surgery, radiation therapy and chemotherapy; these dogs had a median survival time of 261 days (range: 223‐653 days). Cause of death in all cases that survived the initial postoperative period was euthanasia secondary to confirmed or suspected tumor regrowth. The results of this study suggest that definitive radiation therapy, possibly combined with concurrent chemotherapy, significantly improves survival in dogs treated with palliative decompressive surgery for vertebral OSA and should be the treatment of choice in selected cases.     

Severe gastrointestinal bleeding secondary to lornoxicam in the dog

Six dogs with lornoxicam induced severe gastrointestinal bleeding are described. The ingested dose ranged between 0.5 - 5.1?mg/kg BW (median 0.63?mg/kg BW). The severity of the bloodloss anemia was moderate to severe with PCV values ranging between 12 - 27 % (median 16 %) and serum albumin concentrations between 12 - 22 g/l (median 16 g/l). One dog had evidence of chronic thrombocytopathia over 13 days and clinicopathologic findings of gastrointestinal bleeding over 55 days. None of the dogs developed kidney injuries. The clinical condition required transfusion of blood products in 5 of 6 cases. One dog with a perforated duodenal ulcer and septic peritonitis survived until discharge but had to be euthanized later on due to recrudescent clinical signs (hematemesis, melena). The median length of hospitalisation was 12 days (5 - 14). No correlation was seen between the ingested dose and severity of clinical signs. Lornoxicam ingestion leads to severe and longlasting gastrointestinal bleeding in the dog and requires immediate intensive therapy.     

Myoglobin as a prognostic indicator for outcome in dogs with gastric dilatation-volvulus

Objective – To determine whether myoglobin (Mb) is a useful prognostic indicator for outcome and to investigate any relationship between Mb and mortality in dogs with gastric dilatation‐volvulus (GDV). Design – Prospective study. Setting – Veterinary teaching hospital. Animals – Seventy‐two dogs with GDV. Interventions – Blood sampling. Measurements and Main Results – Mb levels were measured at the time of diagnosis (Mbt₀), 24 hours (Mbt₁), and 48 hours (Mbt₂) after signs of GDV were recognized. Fifty‐seven dogs survived (group I) and 15 dogs did not survive (group II). Mb t₀ differed significantly between groups (P=0.04). Mbt₀ in group I ranged from <30 to >700 ng/mL (n=57, median 74 ng/mL), and in group II from 34 to >700 ng/mL (n=15, median 238 ng/mL). Analysis of a receiver operating characteristic curve of Mbt₀ suggested that the best single cutpoint would be 168 ng/mL (sensitivity 60.0%, specificity 84.2%). Fifty percent of dogs with Mbt₀>168 ng/mL were euthanized, while 88.9% with Mbt₀<168 ng/mL survived. Mbt₁ and Mbt₂ differed significantly between groups I and II. Mbt₁ in group I ranged from 32 to >700 ng/mL (n=55, median 123 ng/mL), and Mbt₁ in group II ranged from 131 to 643 ng/mL (n=7, median 343 ng/mL) (P=0.006). Mbt₂ in group I ranged from 30 to 597 ng/mL (n=54, median 101 ng/mL), and in group II from 141 to >700 ng/mL (n=8, median 203 ng/mL) (P=0.02). Conclusions – In this study, Mbt₀ is a moderately sensitive and specific prognostic indicator. Almost 90% of the dogs below the cutpoint survived to discharge, whereas 50% with Mbt₀ above the cutpoint did not survive.     

Hematologic changes associated with half-body irradiation in dogs with lymphoma

BACKGROUND: Reports describe the technique and efficacy of half-body irradiation (HBI) of dogs with lymphoma, but few describe the distinctive toxicoses associated with the combination of HBI and chemotherapy. HYPOTHESIS: HBI would transiently affect myelocytic and erythroid variables as assessed by serial analysis of complete blood counts. ANIMALS: Twenty-nine dogs with lymphoma treated with HBI during 2002 and 2003. METHODS: A retrospective study of medical records of 29 dogs was performed. Two HBI protocols were used, resulting in delivery of either 6 Gy or 8 Gy to each half of the body, 1 month apart. Dogs received chemotherapy before, during, or after irradiation, or at multiple times. Serial hematology was available for all dogs. Data were analyzed between collection periods by analysis of variance (ANOVA) RESULTS: The mean granulocyte count significantly (P < .01) decreased from 10,017 cells/microL (data range 3,001-20,170 cells/ microL) before the first radiation treatment to 3,250 cells/microL (820-4,400 cells/microL) at week 5 (P < .01). Three weeks after this nadir, the mean increased to 10,150 cells/microL (900-26,700 cells/microL). The hematocrit did not change (36-38%). Thrombocytopenia (<100,000/microL) occurred in 10 dogs. Two dogs died because of complications associated with thrombocytopenia. No significant difference in toxicity was found between the 6 Gy and 8 Gy group. CONCLUSIONS AND CLINICAL IMPORTANCE: HBI was myelosuppressive but effects were short term and resolved in 22 of 24 dogs. Further studies are needed to elucidate the safety and role of HBI in the treatment of dogs with lymphoma.     

Use of a centrifugation-based, point-of-care device for production of canine autologous bone marrow and platelet concentrates

OBJECTIVE: To analyze a centrifugation-based, point-of-care device that concentrates canine platelets and bone marrow-derived cells. ANIMALS: 19 adult sexually intact dogs. PROCEDURES: Anticoagulated peripheral blood (60 mL) and 60 mL of anticoagulated bone marrow aspirate (BMA) were concentrated by centrifugation with the centrifugation-based, point-of-care device to form a platelet and a bone marrow concentrate (BMC) from 11 dogs. Blood samples were analyzed on the basis of hemograms, platelet count, and PCV. The BMA and BMC were analyzed to determine PCV, total nucleated cell count, RBC count, and differential cell counts. The BMC stromal cells were cultured in an osteoinductive medium. Eight additional dogs were used to compare the BMC yield with that in which heparin was infused into the bone marrow before aspiration. RESULTS: The centrifugation-based, point-of-care device concentrated platelets by 6-fold over baseline (median recovery, 63.1%) with a median of 1,336 x 10(3) platelets/microL in the 7-mL concentrate. The nucleated cells in BMCs increased 7-fold (median recovery, 42.9%) with a median of 720 x 10(3) cells/microL in the 4-mL concentrate. The myeloid nucleated cells and mononuclear cells increased significantly in BMCs with a significant decrease in PCV, compared with that of BMAs. Stromal cell cultures expressed an osteoblastic phenotype in culture. Infusion of heparin into the bone marrow eliminated clot formation and created less variation in the yield (median recovery, 61.9%). CONCLUSIONS AND CLINICAL RELEVANCE: Bone marrow-derived cell and platelet-rich concentrates may form bone if delivered in an engineered graft, thus decreasing the need for cancellous bone grafts.