Search

Objective: To report the occurrence of neutropenia in dogs with suspected acute hemorrhagic diarrhea syndrome (AHDS) and to assess its association with survival. Secondary objectives were to assess whether neutropenia was associated with length of hospitalization, fulfillment of systemic inflammatory response syndrome (SIRS) criteria, and whether SIRS status was associated with survival. Finally, the association of antimicrobial use with neutropenia, SIRS status, and survival was evaluated., Design: Single-center, retrospective study from the medical records of dogs diagnosed with AHDS between 2017 and 2022., Setting: Private referral hospital., Animals: Fifty-four dogs with suspected AHDS referred to the Emergency and Critical Care specialist service., Interventions: None., Measurements and Main Results: Of 54 dogs, 28 (52%) presented with or developed neutropenia during their treatment course. Overall, 9 (17%) dogs were nonsurvivors. A total of 8 of 28 (29%) dogs with neutropenia were nonsurvivors, while only 1 of 26 (4%) dogs with a normal neutrophil count was a nonsurvivor (P = 0.025). Upon hospital admission, neutropenic dogs were significantly more likely to fulfill SIRS criteria than nonneutropenic dogs (P = 0.0096). There was no difference in mortality between SIRS-positive (fulfilling ≥2 SIRS criteria) and SIRS-negative (fulfilling <2 SIRS criteria) dogs (P = 0.14). There was no difference in the median length of hospitalization between neutropenic and nonneutropenic dogs (P = 0.49)., Conclusions: The incidence of neutropenia is high in this population of dogs presenting with AHDS. In this retrospective study, neutropenia was significantly associated with an increased risk of nonsurvival and an increased likelihood of fulfilling SIRS criteria; however, a fulfillment of SIRS criteria could not be used to predict survival. Neutropenia in dogs with AHDS was not associated with an increased length of hospitalization., (© Veterinary Emergency and Critical Care Society 2025.)

Objectives: To develop and determine the accuracy of a rapid manual technique for the detection of pre-treatment neutropenia (<1.50 × 10 9 /L) in dogs receiving chemotherapy., Materials and Methods: Twenty canine blood smears with known neutrophil counts between 1.00 × 10 9 /L and 3.00 × 10 9 /L were reviewed by two internal medicine clinicians and linear regressions performed to determine a cut-off value for a manual neutrophil count equating to >1.50 × 10 9 /L. Consecutive blood samples from dogs undergoing chemotherapy were processed through an automated haematology analyser (VetScan HM5, Abaxis), and prospective blinded manual review by the same two observers assessed whether the manual technique could accurately detect dogs with neutropenia., Results: Linear regression analysis found a cut-off of >26 neutrophils per 10 low power fields at the monolayer to be equivalent to a neutrophil count of >1.5 × 10 9 /L. A total of 183 blood samples from 43 dogs were reviewed. Automated techniques detected neutropenia in 16 of 183 (9%) blood samples. Using the manual cut-off technique, 13 of 16 (81%) and 11 of 16 (69%) of neutropenic samples were correctly identified by observer 1 and observer 2, respectively. Twenty-three of 167 non-neutropenic dogs (14%) were incorrectly classified as neutropenic by observer 1, and 27 (16%) by observer 2. Inter-observer agreement was 92%. Sensitivity was 81% (95% confidence interval 54% to 96%) for observer 1 and 69% (95% confidence interval 41% to 89%) for observer 2. Specificity was 86% (95% confidence interval 80% to 91%) for observer 1 and 84% (95% confidence interval 77% to 89%) for observer 2., Clinical Significance: Manual estimation resulted in up to five of 16 (31%) neutropenic samples being incorrectly classified. A full automated differential cell count remains preferable., (© 2024 British Small Animal Veterinary Association.)

Vincristine sulphate, a microtubule inhibitor, is used extensively in veterinary oncology for treating lymphoma. Neutropenia during multiagent protocols is a common reason for treatment delay and reduced dose intensity. This study evaluated toxicities associated with treating systemically well neutropenic lymphoma patients with vincristine. Lymphoma patients undergoing CHOP were evaluated retrospectively for instances of vincristine administration when absolute neutrophil counts (ANC) were 1.5 × 10 9 /L or below. Instances of vincristine administration when ANC was equal to or less than 1.5 × 10 9 /L were compared to vincristine administration where ANC was greater than 1.5 × 10 9 /L in the same patient. Univariate and multivariate modelling compared VCOG-CTCAE v1.1 grading of vomiting, diarrhoea, anorexia and 7-day neutrophil nadir between groups. The median dose of vincristine administered was 0.7 mg/m 2 for both study groups. A total of 112 doses of vincristine were administered to neutropenic patients (grade 2 n: 76, grade 3 n: 26, and grade 4 n: 10). These were compared to 223 doses of vincristine administered to the same patients when ANC was above 1.5 × 10 9 /L. Neutropenic administration was most prevalent 7 days following cyclophosphamide administration. Day 7 post-administration neutropenia was more prevalent in patients with ANC greater than 1.5 × 10 9 /L at the time of vincristine administration (neutropenic 9%; non-neutropenic 18%). Relative risk of 7-day neutropenia, vomiting, diarrhoea, and anorexia was similar between groups on multivariate analysis. Patients with lymphoma who receive vincristine when ANC is 1.5 × 10 9 /L or below are at no greater risk of adverse effects than the same patient who receives vincristine when neutrophil counts are greater than 1.5 × 10 9 /L., (© 2024 John Wiley & Sons Ltd.)

Neutropenia is a common chemotherapy-associated adverse event (AE) in dogs and a significant cause of decreased relative dose intensity. Dose reductions (DRs) and treatment delays (TDs) are frequently applied to decrease the risk of further neutropenic events (NEs) and AEs, but there is no standardised approach. The two main objectives of this retrospective study were to determine: (1) the failure rate of a 10% DR to prevent a subsequent inadequate absolute neutrophil count (ANC), defined as a nadir ANC <0.75 × 10 9 /L or pretreatment ANC <1.5 × 10 9 /L; and (2) if the duration of TDs due to pretreatment neutropenia affects the occurrence of subsequent NEs. A total of 1056 chemotherapy treatments were recorded for 128 dogs that developed at least one NE. In 75 of 124 (60.5%, 95% CI: 51.2%-69%) evaluable NEs, a nadir ANC of ≥0.75 × 10 9 /L and pretreatment ANC of ≥1.5 × 10 9 /L were achieved after a single 10% chemotherapy DR, while a 10% DR failed to prevent a subsequent inadequate ANC in the remaining 49/124 (39.5%, 95% CI: 30.1%-48.3%). The only variable associated with failure was the drug prescribed. DR failure occurred in 22/39 (56.4%, 95% CI: 40.9%-70.6%) lomustine DRs, 14/27 (51.9%, 95% CI: 33.9%-69.2%) cyclophosphamide DRs, but only 2/22 (9.1%, 95% CI: 2.5%-27.8%) doxorubicin DRs and 2/24 (8.3%, 95% CI: 2.3%-25.8%) vincristine DRs. Seventy-three evaluable TDs (mean: 5 days, SD ± 2.2 days) were prescribed. There was no association between TD duration and subsequent NEs (p = 0.11)., (© 2024 The Author(s). Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

Objective: To determine the clinical significance of performing repeated postchemotherapy CBC for cancer-bearing dogs receiving ≥ 4 carboplatin treatments. The secondary aim was to identify risk factors associated with cumulative carboplatin-induced neutropenia in those dogs., Animals: 40 client-owned dogs diagnosed with cancer., Methods: A retrospective study using medical records from a single academic institution during 2012 to 2023. Dogs that received ≥ 4 doses of carboplatin with pre- and postchemotherapy CBCs available were included. Signalment and possible risk factors were recorded. Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events was used for neutropenia grading., Results: 40 dogs met the inclusion criteria, with a total of 206 prechemotherapy and 188 postchemotherapy CBC results available. The median carboplatin dosage was 300 mg/m2 (range, 200 to 300 mg/m2). The median interval between carboplatin administration and the postchemotherapy CBC was 10 days (range, 6 to 38 days). Eleven dogs developed a grade 2 or higher neutropenia, with 5 dogs developing multiple neutropenic events, for a total of 18 separate events (18/394). Only 2 of 18 neutropenic events were recorded at the 10- to 14-day postchemotherapy CBC. The yield of detecting neutropenia at a postchemotherapy CBC at any carboplatin chemotherapy after the second dose was < 1% (1/149). Dogs that developed neutropenia at the pre-2nd chemotherapy CBC had a significantly higher risk of developing another neutropenic event at subsequent prechemotherapy CBC (P < .001)., Clinical Relevance: The incidence of cumulative neutropenia after 4 to 6 doses of carboplatin is low in cancer-bearing dogs. If a grade 2 or higher neutropenia is observed at or before the second prechemotherapy CBC, the dog is at a higher risk of developing neutropenia following future treatments.

Objectives: This study aimed to evaluate clinical signs, diagnostic findings, treatment administered and short- (survival to 28 days) and long-term prognosis (survival >6 months) in dogs diagnosed with trapped neutrophil syndrome., Materials and Methods: Medical records of 12 dogs (10 Border Collies and two Border Collie Crossbreeds) homozygous for VPS13B gene mutation causing trapped neutrophil syndrome from seven veterinary institutions between January 2011 and June 2022 were evaluated retrospectively., Results: The most common clinical signs at the time of diagnosis were pyrexia, abnormal gait and gastrointestinal signs. Concurrent metaphyseal osteopathy and immune-mediated polyarthritis were common. Seven dogs had a segmented neutrophil count below, four dogs within and one dog above the analyser reference interval at presentation. Two dogs had a septic source identified and both were additionally identified to be homozygous mutant positive on DNA testing by polymerase chain reaction (PCR) for canine cyclic neutropenia. All dogs received at least one antimicrobial agent and 10 dogs received treatment with prednisone or prednisolone (median starting dose 1 mg/kg/day; range 0.5 to 2.5 mg/kg/day). Nine dogs were alive at 28 days and six dogs were alive at 6 months post-diagnosis., Clinical Significance: Trapped neutrophil syndrome should be suspected in young Border Collies with pyrexia, lameness and gastrointestinal signs. Neutropenia may not always be present and long-term survival is possible. A septic focus was not commonly identified in our population; however, our results suggest that if identified, testing for concurrent canine cyclic neutropenia should be considered., (© 2024 British Small Animal Veterinary Association.)

Background: Traditional dosing of chemotherapy drugs based on body surface area may overdose small dogs, leading to an increased frequency of adverse events (AEs)., Hypothesis/objectives: Evaluate the frequency of hematologic and gastrointestinal AEs in dogs with newly diagnosed lymphoma treated with vincristine weighing ≤15 kg in comparison to dogs weighing >15 kg. We hypothesized that dogs weighing ≤15 kg would experience a higher frequency of AEs., Animals: One hundred and thirty-eight dogs with newly diagnosed lymphoma were treated with vincristine., Methods: A multicenter retrospective study reviewing hematologic data and medical record information. Complete blood counts were performed no more than 24 hours before vincristine administration and then between 4 and 8 days post-administration. Data were evaluated using logistic regression or ordinal logistic regression., Results: Thirty-eight dogs weighing ≤15 kg and 100 dogs weighing >15 kg were included. The median vincristine dose for both groups was 0.6 mg/m 2 . Seventeen (12.3%) instances of neutropenia occurred with no significant difference in overall frequency or grade between groups. Thirty initially asymptomatic substage A dogs (29.4%) experienced gastrointestinal AEs. Because of the widespread use of gastrointestinal supportive care medications, statistical comparison between groups could not be performed. Seven instances of hospitalization occurred (5.0%) and the risk of hospitalization did not differ significantly between groups (P = .37)., Conclusions and Clinical Importance: Vincristine dosed at ≤0.6 mg/m 2 does not increase the risk of hematologic AEs in dogs weighing ≤15 kg., (© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Only one report on the successful use of filgrastim (granulocyte colony-stimulating factor) in cats for severe neutropenia following azathioprine toxicity exists. Here, we report on a case in which a cat was prescribed methimazole but the medication was filled incorrectly with azathioprine tablets and the prescription label indicated a methimazole dosing regimen that was administered for three days before recognition of the error. On presentation, the cat's physical examinations were consistent with previous examinations before ingestion of azathioprine. A complete blood cell count revealed neutropenia and leukopenia. The cat later developed hyporexia, dehydration, and vomiting. Treatment included antinausea and appetite stimulant medications, filgrastim, and antibiotics. Filgrastim given as subcutaneous injections over the course of treatment increased neutrophil cell counts after suppression. The cat made a full recovery after responding to the treatment protocol. Based on the perceived response to filgrastim in this single feline case report, its use can be considered for the treatment of azathioprine-induced neutropenia in cats., (© 2024 by American Animal Hospital Association.)

A mixed-breed, 8-year-old male dog developed neutropenia, thrombocytopenia, and hyperglobulinemia. Bone marrow hyperplasia and splenic plasmacytosis were cytologically observed. The dog had never been outside of Tokyo or Shizuoka Prefecture. Splenectomy was performed to confirm and remove the cause of splenic plasmacytosis. A histopathological diagnosis of splenic plasmacytoma was made; however, serum protein electrophoresis showed polyclonal gammopathy. Further screening was performed, and Ehrlichia canis infection was confirmed. The dog was treated with doxycycline for 5 weeks. After the antibiotic therapy, no relapse of neutropenia, thrombocytopenia, hyperglobulinemia, or positive polymerase chain reaction result of E. canis infection was observed for 3 years. Careful attention should be given to ehrlichiosis when exploring the cause of pancytopenia or hyperglobulinemia, regardless of the travel history.

Large granular lymphocyte lymphoma (LGLL) is a rare form of lymphoma in dogs. Limited information exists regarding presentation, treatment response, and outcome. The aim of this single-institute, retrospective study was to characterise clinical presentation, biologic behaviour, outcomes, and prognostic factors for dogs with LGLL. Cytologic review was also performed. Sixty-five dogs were included. The most common breed was the Labrador retriever (29.2%), and the most common presenting signs were lethargy (60.0%) and hyporexia (55.4%). The most common primary anatomic forms were hepatosplenic (32.8%) and gastrointestinal (20.7%). Twenty dogs (30.8%) had peripheral blood or bone marrow involvement. Thirty-two dogs were treated with maximum tolerated dose chemotherapy (MTDC) with a response documented in 74.1% of dogs. Dogs ≥7 years, and those with neutropenia or thrombocytopenia at diagnosis had the reduced likelihood of response to treatment. For dogs treated with MTDC median progression-free interval (PFI) was 17 days (range, 0-481), the median overall survival time (OST) 28 days (range, 3-421), and the 6-month and 1-year survival rates were 9.4% and 3.1%, respectively. On multivariable analysis, monocytosis and peripheral blood involvement were significantly associated with shorter PFI and OST. Long-term survival (≥100 days) was significantly associated with intermediate lymphocyte size on cytology. Dogs with LGLL have moderate response rates to chemotherapy but poor overall survival. Additional studies are needed to further evaluate prognostic factors and guide optimum treatment recommendations., (© 2023 The Authors. Veterinary and Comparative Oncology published by John Wiley & Sons Ltd.)

Background: Phenobarbital (PB) is used as a first-line treatment for recurrent epileptic seizures in cats. While hematologic abnormalities are well-known side effects of antiepileptic therapy with PB in humans and dogs, little is known about such alterations in cats., Objectives: The aim of this retrospective study was to investigate the prevalence and clinical relevance of cytopenia during PB treatment in cats., Methods: In this single-center, retrospective clinical study, 69 cats-with suspected idiopathic epilepsy admitted to the Small Animal Clinic of the University of Veterinary Medicine in Vienna (VMU)-were included. A complete blood count for each patient was performed, and changes in hematocrit, leukocytes, neutrophils, and thrombocytes were documented and graded., Results: Fifty-three out of 69 cats (76.8%) showed cytopenias with a reduction of at least one cell fraction during PB treatment. The most frequent change was neutropenia (60%), followed by leukopenia (49.3%), thrombocytopenia (24.1%), and anemia (20.3%). Most of the changes were mild or moderate; only one patient (1.5%) showed severe leukopenia and neutropenia, and one was a life-threatening neutropenia (1.5%) with a serum PB concentration within or even below the therapeutic range. These patients did not present with clinical symptoms other than those related to epileptic episodes. Cats who received combination therapy showed lower hematocrits than those who received monotherapy. A tendency for leukocytes and neutrophils to decrease during PB treatment was also seen., Conclusions: Blood cytopenias may frequently occur in cats on chronic PB therapy, even when serum drug levels are within the therapeutic range. However, clinical signs are typically mild to moderate and rarely severe., (© 2023 The Authors. Veterinary Clinical Pathology published by Wiley Periodicals LLC on behalf of American Society for Veterinary Clinical Pathology.)

Background: This study was performed to determine the ability to escalate drug doses in a 15-week CHOP protocol in dogs with multicentric lymphoma., Hypothesis: We hypothesized that at least 50% of dogs could successfully be escalated in at least 1 drug. Secondary aims were to establish objective response rate (ORR), progression-free interval (PFI), and overall survival time (OST)., Animals: Thirty dogs with newly diagnosed multicentric lymphoma were prospectively treated with a 15-week CHOP protocol., Methods: This was a prospective cohort study. Drug doses that did not cause dose-limiting adverse effects (AEs) were increased using a standardized escalation protocol. AEs and response were assessed using VCOG criteria. Serial blood samples were collected after the first dose of each drug for pharmacokinetic analysis., Results: Of the 23 dogs with the opportunity to dose escalate, at least 1 drug was successfully escalated in 18 (78%). Vincristine was successfully escalated to 0.8 mg/m 2 or higher in 11 dogs, cyclophosphamide to 300 mg/m 2 or higher in 16 dogs, and doxorubicin to 35 mg/m 2 or 1.4 mg/kg or higher in 9 dogs. Three of the 23 dogs (13%) were hospitalized at least once because of drug-induced AEs. Neutropenia was the most common dose-limiting toxicosis for all drugs. Peak doxorubicin concentrations were significantly lower in dogs where doxorubicin was successfully escalated. The objective response rate was 100%. The median progression free interval was 171 days. The median overall survival time was 254 days., Conclusions: Drugs in the CHOP protocol can often be escalated safely with manageable AEs., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

A 3-year-old male pit bull terrier was presented for a 4-day history of progressive tetraparesis and cervical pain. Magnetic resonance imaging confirmed an extradural mass within the left lateral vertebral canal extending from caudal C5 to mid-T2. Lumbar cerebrospinal fluid (CSF) demonstrated marked (90%) eosinophilic inflammation. A C6-7 dorsal laminectomy and C7-T2 left hemilaminectomy were done, with gross disease remaining. Histopathology revealed a large T cell lymphoma with marked eosinophilic infiltration. The dog underwent CHOP-based chemotherapy with resolution of clinical signs, with a similar course of therapy performed at recurrence 37 months after initial presentation. The dog was euthanized 39 months after presentation for multiorgan failure secondary to neutropenic sepsis and aspiration pneumonia. This represents a positive long-term response to multimodal treatment of extradural T-cell lymphoma within the vertebral canal associated with a marked CSF eosinophilia., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Copper-associated hepatitis in dogs results from elevated copper levels secondary to increased intake or decreased clearance. Treatment is through establishing a negative copper balance and can include chelation therapy. Traditionally, chelation therapy in dogs is uses D-penicillamine, which has been shown to have severe side effects in humans. Side effects have not been well-documented in dogs but can include nephrotoxicity and dermatologic reactions. This article is the first to report neutropenia in a dog secondary to chelation therapy using D-penicillamine. In this case, a complete blood (cell) count (CBC) collected before initiation of chelation therapy was normal and neutropenia was documented 4 mo after starting therapy. A cytologic examination of bone marrow confirmed a myeloid hypoplasia. Following discontinuation of D-penicillamine, the neutropenia resolved. Based on this case report, periodic CBC rechecks following the initiation of D-penicillamine chelation therapy are recommended to guide treatment decisions. Key clinical message: Dogs with confirmed copper-associated hepatitis should be treated cautiously with D-penicillamine for chelation therapy. D-penicillamine may adversely affect bone marrow, causing a leukopenia characterized by neutropenia. It is recommended that clinicians periodically monitor neutrophil counts while treating dogs with D-penicillamine., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Babesiosis and ehrlichiosis are the most clinically significant tick-borne infections in dogs. Although epidemiological investigations of these diseases have been performed in some Asian regions, little data is available in Hong Kong, where competent vector tick species are endemic. The objectives of this study were to determine the molecular prevalence of Ehrlichia canis and Babesia species (B. canis, B. gibsoni, B. vogeli) in owned dogs suspected of tick-borne infection in Hong Kong and to identify risk factors associated with B. gibsoni infection. Electronic records from the Veterinary Diagnostic Laboratory of City University of Hong Kong were searched to identify canine blood samples submitted for molecular testing of these pathogens by real time PCR between March 2018 and May 2021. Electronic patient records from the affiliated veterinary hospital were searched to identify a subset of tested dogs to investigate the potential risk factors for B. gibsoni infection using logistic regression models. Among 1508 tested dogs for all four pathogens of interest, Babesia spp. were detected in 435 (28.8%) and E. canis in 112 (7.4%). Babesia gibsoni was detected in 408 dogs while B. vogeli was detected in 27 dogs. Babesia canis was not detected in any dog. Co-infections of different combinations of B. gibsoni, B. vogeli and E. canis were present in 25 dogs. In multivariable logistic regression, mixed breed dogs were more likely to be infected with B. gibsoni than purebreds (P = 0.005), while dogs > 10 years of age were less likely to be infected than younger dogs (P = 0.019). Hematological abnormalities significantly associated with B. gibsoni infection included thrombocytopenia, neutropenia, or pancytopenia. Babesiosis caused by B. gibsoni is a common infection in owned dogs suspected of tick-borne infection in Hong Kong. The risk factors reported should be considered in diagnosing dogs suspected of infection with this agent. Furthermore, consideration for testing for B. gibsoni infection should be given if the results of a complete blood count show thrombocytopenia even in the absence of anemia, neutropenia or pancytopenia., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Objective: To evaluate the use of a modified Sepsis-3 (mSepsis-3) definition compared to the currently used modified Sepsis-2 (mSepsis-2) definition to determine whether the mSepsis-2 or mSepsis-3 stratifications were able to identify populations of dogs ultimately more likely to die from canine parvovirus (CPV) infection., Design: Retrospective, January 2009 to March 2020., Setting: A private, small animal, urban, referral emergency and specialty hospital., Animals: Fifty-nine client-owned dogs hospitalized for treatment of CPV., Interventions: None., Measurements and Main Results: Dogs were divided into mSepsis-2 and mSepsis-3 categories based on the highest level of illness severity reached during hospitalization. Greater illness severity based on mSepsis-2 criteria (ie, sepsis, severe sepsis, septic shock) was associated with an increase in average length of stay (P < 0.001), increase in average cost of stay (P < 0.01), and presence of leukopenia (P < 0.05). An increase in illness severity within the mSepsis-2 criteria was not associated with hyperlactatemia (P = 0.29), presence of neutropenia (P = 0.12), or mortality (P = 0.35). Greater illness severity based on mSepsis-3 criteria (ie, infection only, sepsis, septic shock) was associated with an increase in mortality (P < 0.05), increase in average length of stay (P < 0.001), increase in average cost of stay (P < 0.01), presence of leukopenia (P < 0.01), and presence of neutropenia (P < 0.05). The mSepsis-3 criteria were not associated with the presence of hyperlactatemia (P = 0.68). There was no significant difference between survivors and nonsurvivors in the presence of leukopenia (P = 0.19), neutropenia (P = 0.67), or hyperlactatemia (P = 0.58)., Conclusions: The mSepsis-3 diagnostic criteria appear to better identify dogs with CPV at higher risk for mortality compared to the mSepsis-2 criteria., (© Veterinary Emergency and Critical Care Society 2022.)

An 8-wk-old, male, mixed-breed puppy was adopted from a rescue organization. From the time of adoption, the puppy suffered episodes of illness affecting various organ systems, which resolved with supportive therapy but relapsed once medical therapy was discontinued. Review of the hematologic data revealed cyclic fluctuations in circulating blood cells. Cyclicity was most prominent in neutrophils, with recurrent severe neutropenia. Neutropenic episodes lasted 5-6 d, with regular cycles of 11-14 d between nadir neutrophil counts. Genetic testing determined that the patient was homozygous mutant for the frameshift mutation in the adaptor protein complex 3 β-subunit ( AP3B1 ) gene, originally identified in gray collies with cyclic hematopoiesis (CH). Pedigree information was not available, but the patient's features were phenotypically distinct from those of collies. We describe here a case of the AP3B1 mutation in a mixed-breed dog that did not resemble a collie, undescribed previously, to our knowledge. Our findings indicate that the AP3B1 mutation and CH are present within the general canine population and are not restricted to collies.

Trapped neutrophil syndrome is a rare congenital disease recognized in Border Collies and is characterized by persistent neutropenia with myeloid hyperplasia. The mechanism of neutropenia has not been described. We document the case of a young Border Collie diagnosed with trapped neutrophil syndrome based on clinical features, blood and bone marrow evaluation, and presence of the associated homozygous mutation. Results from flow cytometric and storage studies suggested lower neutrophil survival time. The dog had substantial neutrophilic inflammation in multiple organs, indicating that neutrophils could leave the marrow and enter tissues, making the term "trapped" neutrophil syndrome a misnomer., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of Wiley Periodicals LLC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Lomustine (1-[2-chloroethyl]3-cyclohexyl-1-nitrosurea, CCNU) is an oral alkylating agent in the nitrosourea subclass that can cause myelosuppression, with neutropenia being the main dose-limiting toxicity. The aim of this study was to define the frequency of neutropenic events and to identify predisposing risk factors in tumour-bearing dogs treated with CCNU. Dogs receiving CCNU for various malignancies were identified following a search of hospital databases. Variables analysed for correlation with neutropenia included signalment, body weight, tumour type, CCNU total dose, steroid use, protocol type, use of L-asparaginase, previous anthracycline administration and use of the drug as first-line or in the rescue setting. One-hundred and fifteen cases were included; median age was 7 years (range 1-14 years) and median body weight 27.6 kg (range 3-74 kg). The median CCNU dose was 63.5 mg/m 2 (range 27.7-84.9 mg/m 2 ). Neutropenia occurred in 75 cases (65%) and was comprised of grade 1 (28%), 2 (16%), 3 (29.3%) and 4 (26.7%) events. Tumour type (histiocytic sarcoma [HS]), use of CCNU first line, dose >70 mg/m 2 , absence of co-morbidities and previous anthracycline administration, were significantly associated with an increased risk of developing neutropenia, including high-grade events. There was a 1.7% reported mortality rate. When CCNU is used in dogs with HS, first-line, at a starting dosage >70 mg/m 2 , in patients with no co-morbidities or with a history of previous anthracycline administration, there may be an increased risk of developing neutropenia. These data may help guide treatment decisions and minimize treatment delays or potentially life-threatening complications., (© 2022 John Wiley & Sons Ltd.)

Background: The recommended doxorubicin (DOX) dose for small dogs is 1 mg/kg. Recent data suggest that DOX-induced gastrointestinal (GI) toxicosis can be reduced with maropitant treatment., Objectives: To investigate the incidence of adverse events (AEs) in small-breed dogs administered a single 25 mg/m 2 DOX followed by administration of maropitant (DOX25). The primary aim was to assess myelo- and GI toxicoses for 2 weeks after DOX administration. The secondary aim was to compare the incidence and grades of AEs found in the DOX25 group with a historical control group (DOX 1 mg/kg without administration of antiemetic or antidiarrheal medications)., Animals: Nineteen small-breed tumor-bearing dogs., Methods: A prospective, observational study of tumor-bearing dogs, weighing 5 to 10 kg, administered a single 25 mg/m 2 dose of DOX IV, followed by administration of maropitant for the next 5 days., Results: Inappetence, vomiting, and diarrhea were found in 7/19, 2/19, and 6/19 of the DOX25 dogs, respectively. Neutropenia and thrombocytopenia was 12/19 and 3/19, respectively. Most AEs were grades 1 and 2, except for grades 3 and 4 inappetence and neutropenia in 3 and 4 dogs, respectively. Furthermore, febrile neutropenia occurred in 3/19 dogs in the DOX25 group. All AEs between the DOX25 and historical control groups were not significantly different., Conclusions and Clinical Importance: Vomiting and diarrhea were deemed acceptable with 25 mg/m 2 DOX followed by maropitant treatment in 5 to 10 kg dogs; however, additional supportive care might be needed for dogs with inappetence and neutropenia., (© 2022 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

A 4-year-old, castrated male, Russian blue cat with idiopathic epilepsy was diagnosed with neutropenia. The neutropenia was classified as idiopathic after blood tests and abdominal imaging did not reveal an infectious, inflammatory or neoplastic aetiology. As a treatment trial for idiopathic neutropenia, the cat was administered granulocyte colony-stimulating factor by subcutaneous injection once daily for 3 days. Two weeks after completion of granulocyte colony-stimulating factor therapy, the cat developed severe thrombocytopenia, with the granulocyte colony-stimulating factor therapy considered to be the most likely cause. No treatment was initiated, and the thrombocytopenia had resolved spontaneously by 2 weeks after diagnosis. This is the first reported case of transient severe thrombocytopenia in a cat following granulocyte colony-stimulating factor treatment., (© 2021 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Background: Despite multiple reports of chemotherapy overdoses (ODs) in human and veterinary medicine, anthracycline ODs have been described infrequently., Hypothesis/objectives: Describe toxicities, treatments, and overall outcome after anthracycline OD in dogs., Animals: Twelve mitoxantrone (MTX) and 4 doxorubicin (DOX) ODs were evaluated., Methods: Multicenter retrospective analysis. The American College of Veterinary Internal Medicine oncology and internal medicine listservs were solicited for cases in which a chemotherapy OD occurred., Results: Sixteen anthracycline cases were collected. Anthracycline ODs occurred because of an error in chemotherapy preparation (n = 9), or dose miscalculation (n = 7). The overall median OD was 1.9× (range, 1.4-10×) the prescribed amount. Most ODs were identified immediately after drug administration (n = 11), and the majority of patients were hospitalized on supportive care (n = 11) for an average of 8 days (range, 3-34 days). Adverse events after the OD included neutropenia (94%), thrombocytopenia (88%), anemia (63%), diarrhea (63%), anorexia (56%), vomiting (38%), lethargy (31%), and nausea (25%). Two patients did not survive the OD. High grade neutropenia was common and did not appear to be mitigated by the administration of filgrastim., Conclusions and Clinical Importance: All patients received supportive care after identifying the OD and death was uncommon. Further evaluation is needed to determine ideal therapeutic guidelines anthracycline OD., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Neutrophils are one of the initial cell lines of protection against pathogens, and when their concentrations in the blood are low, animals are highly susceptible to infections. Neutropenia has been reported in cetaceans secondary to administration of systemic sulfa antibiotics or antifungal medications and severe, overwhelming infection. Filgrastim was administered to treat neutropenia over a 15-y period in 11 cetaceans comprising four species-beluga ( Delphinapterus leucas , n = 1), bottlenose dolphin ( Tursiops truncatus , n = 4), killer whale ( Orcinus orca , n = 5), and short-finned pilot whale ( Globicephala macrorhynchus , n = 1)] ranging in age from 1 wk to >24 y. Seven study animals received multiple doses (2-6). All animals responded to at least one dose (1-7 µg/kg) of parenteral filgrastim characterized by an increase in peripheral immature (band) neutrophils, segmented neutrophils, or both. In most cases (9/11), neutrophil counts increased within 48 h of a single dose. Duration of response varied but was at least 2 wk in eight of the 11 animals and 5-9 d in the remaining animals. No adverse reactions were observed in any cases.

Background: Neutropenia is the most common dose-limiting side effect of cytotoxic chemotherapy in cancer-bearing dogs. Biodynamic imaging (BDI) is a functional imaging technology that measures dynamic light scattering from living, three-dimensional tissues to characterize intracellular motion within those tissues. Previous studies have associated BDI biomarkers with tumour sensitivity to chemotherapy agents in dogs with naturally occurring cancer. We hypothesized that BDI, performed ex vivo on bone marrow aspirate samples, would identify dynamic biomarkers associated with the occurrence of specific degrees of neutropenia in tumour-bearing dogs receiving doxorubicin chemotherapy., Materials and Methods: Bone marrow aspirates were collected from 10 dogs with naturally occurring cancers prior to initiation of doxorubicin treatment. BDI was performed on bone marrow samples treated ex vivo with doxorubicin at 0.1, 1, 10 and 100 μM along with 0.1% DMSO as a control. Dogs then were treated with doxorubicin (30 mg/m 2 , intravenously). Peripheral blood neutrophil counts were obtained on the day of treatment and again 7 days later. Receiver operating characteristic curves identified provisional breakpoints for BDI biomarkers that correlated with specific changes in neutrophil counts between the two time points., Results: Provisional breakpoints for several BDI biomarkers were identified, specifying dogs with the largest proportionate change in neutrophils and with neutropenia that was grade 2 or higher following doxorubicin treatment., Conclusions: Biodynamic imaging of bone marrow aspirates may identify those dogs at greater risk for neutropenia following doxorubicin chemotherapy. This approach may be useful for pre-emptively modifying chemotherapy dosing in dogs to avoid unacceptable side effects., (© 2020 The Authors Veterinary Medicine and Science Published by John Wiley & Sons Ltd.)

Background: Neutropenia is an adverse effect of vincristine when used in multidrug chemotherapy protocols., Objective: To determine the incidence of neutropenia, identify potential risk factors for neutropenia, and determine the effect of neutropenia on outcome, in dogs receiving vincristine for treatment of immune-mediated thrombocytopenia (ITP)., Animals: One hundred twenty-seven client-owned dogs presumptively diagnosed with ITP., Methods: In this retrospective cohort study, medical records were reviewed to identify dogs presumptively diagnosed with ITP, and treated with vincristine, over a 15-year period. Logistic regression was used to identify risk factors for the development of neutropenia in dogs receiving vincristine. Time to platelet count ≥40 000 platelets/μL, survival, and duration of hospitalization were compared between neutropenic and non-neutropenic dogs., Results: Vincristine was administered to 127 dogs with presumptive ITP; 19 became neutropenic. Administration of cyclosporine was significantly (P < .001) associated with the development of neutropenia (odds ratio: 12.97, 95% confidence interval: 4.17, 40.35). There was no difference in median time to ≥40 000 platelets/μL between neutropenic dogs (4 days; range, 1-14 days) and non-neutropenic dogs (3 days; range, 0-48 days). Percentage survival to discharge was 95% in both groups, but median duration of hospitalization was significantly longer in neutropenic dogs (6 days; range, 3-22 days) compared to non-neutropenic dogs (4 days; range, 2-15 days)., Conclusions and Clinical Importance: Cyclosporine administration was associated with the development of neutropenia in dogs receiving vincristine, which might be related to effects on metabolism of vincristine. Neutrophil counts should be monitored in dogs receiving vincristine treatment for ITP, particularly if administered in conjunction with cyclosporine., (© 2021 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)

Smaller dogs are known to have an increased risk of chemotherapy-induced myelosuppression for doxorubicin, mitoxantrone and melphalan. This retrospective study aimed to determine if dogs <15 kg and <10 kg experienced greater degrees of myelosuppression following treatment with carboplatin chemotherapy compared with dogs ≥15 kg. One hundred and one dogs treated with carboplatin for a variety of malignancies were retrospectively analysed. Eight dogs (61%) weighing <10 kg, three (38%) weighing 10 kg to <15 kg and 14 (17%) weighing ≥15 kg experienced a grade 3 or 4 neutropenia. Five dogs (38%) weighing <10 kg, two (25%) weighing 10 kg to <15 kg and 13 (16%) weighing ≥15 kg experienced a grade 3 or 4 thrombocytopenia. Dogs <10 kg were significantly more likely to develop a grade 3 or 4 neutropenia following carboplatin than dogs ≥10 kg (3.5 RR; 95% CI, 1.9-6.3; P < .001). Dogs <15 kg were also significantly more likely to develop a grade 3 or 4 neutropenia than dogs ≥15 kg (3 RR; 95% CI, 1.6-5.6; P = .004). Dogs <10 kg were significantly more likely to develop a grade 3 or 4 thrombocytopenia than those dogs ≥10 kg (2.5 RR; 95% CI, 1.1-5.6; P = .006). Hospitalization was significantly more likely for dogs <10 kg vs ≥10 kg (P = .014) as well as for dogs <15 kg vs ≥15 kg (P = .039). This study demonstrates an increased risk of carboplatin-induced myelosuppression in dogs <15 kg, and particularly those <10 kg. This information should be considered by clinicians when making decisions regarding the initial carboplatin dose for smaller canine patients, especially those <15 kg., (© 2020 John Wiley & Sons Ltd.)

Absolute neutrophil count (ANC) cut-offs for antimicrobial prophylaxis in veterinary cancer chemotherapy patients are empirical and vary between institutions. Evidence based cut-offs are vital for antimicrobial stewardship, particularly as global antimicrobial resistance rises. The primary objectives of this study were to evaluate the tolerability of a <0.75 × 10 9 /l ANC cut-off for antimicrobial prophylaxis in dogs after receiving chemotherapy and its impact on antimicrobial prescription. Predicted nadir ANCs (pnANCs) were stratified into six groups (<0.75 × 10 9 /l [receiving antimicrobial prophylaxis], 0.75-0.99 × 10 9 /l, 1-1.49 × 10 9 /l, 1.5-1.99 × 10 9 /l, 2.0-3.59 × 10 9 /l and 3.6-12 × 10 9 /l [reference interval]). The incidences of post-nadir febrile neutropenia (FN) and non-haematological toxicity (NHT) were compared between groups. Five hundred and eighty-six pnANCs were recorded for 181 dogs. There were four episodes of post-nadir FN and 90 episodes of post-nadir NHT. There was no significant difference in incidence of post-nadir FN (P = .063) or post-nadir NHT (P = .084) between pnANC groups. Antimicrobial prophylaxis was prescribed following 8.8% of the chemotherapy administrations; had cut-off values of <1.0 × 10 9 /l or <1.5 × 10 9 /l been used it would have been prescribed in 15.3% and 25.8% of cases respectively. An ANC cut-off of <0.75 × 10 9 /l for antimicrobial prophylaxis appears to be well tolerated and minimizes the prescription of antimicrobials., (© 2019 John Wiley & Sons Ltd.)

An 8-month-old female domestic shorthair cat was presented to the Animal Medical Center with anorexia, lethargy, and mild gastrointestinal signs. A CBC revealed a profound neutropenia, and serologic testing with an in-house test kit (SNAP FIV/FeLV Combo, IDEXX) was positive for feline leukemia virus (FeLV) antigen. Serial hematologic examinations during hospitalization showed a persistent neutropenia with occasionally severe anemia and thrombocytopenia. Prednisolone administration afforded complete hematologic remission within 3 days. Four weeks after the premature discontinuation of prednisolone, the patient relapsed; however, complete and prolonged hematologic remission was achieved after prednisolone was re-induced. Bone marrow aspiration cytology was consistent with immune-mediated destruction of the mature myeloid cells. steroid-responsive (likely immune-mediated) cytopenias rarely occur in cats with progressive FeLV infection. Although only a few cases of FeLV-positive, severely neutropenic cats that responded to immunosuppressive therapy have been reported, this case highlights that a grave prognosis should not always be given to these FeLV-positive cats., (© 2020 American Society for Veterinary Clinical Pathology.)

A 10 wk old female border collie was presented for hemorrhagic diarrhea and pelvic limb lameness. Examination revealed pain and effusion in multiple appendicular joints and pyrexia. Clinicopathologic testing revealed moderate neutropenia as well as nondegenerate neutrophilic inflammation in multiple joints. Radiographs showed capsular joint swelling and heterogeneous metaphyseal lucencies in the distal radius, ulna, femur, and tibia. Genetic testing confirmed a mutation in the vacuolar protein sorting-associated protein 13B gene and a diagnosis of trapped neutrophil syndrome (TNS). Within 24 hr of initiating prednisone therapy (1 mg/kg, per os , q 12 hr), the dog was afebrile and nonpainful with normal ambulation. Lameness recurred twice over the next 5 mo. At 9 mo of age, diagnostics showed severe erosive polyarthritis of both stifles with an inflammatory leukogram and arthrocentesis findings consistent with septic arthritis, and the dog died despite antibiotic therapy. This is the first case of TNS described in the North American literature, and it is unique in that we had the opportunity to document progression of radiographic abnormalities over more than 6 mo. TNS should be considered in young border collies with signs suggestive of immune-mediated polyarthritis, septic arthritis, or hypertrophic osteodystrophy, combined with neutropenia or gastrointestinal signs.

The objective of this retrospective study was to report treatment outcomes in dogs with histiocytic sarcoma (HS) that were treated with nimustine (ACNU). This study evaluated data from 11 dogs including 5 with macroscopic tumors that were treated in the primary setting and 6 that underwent aggressive local therapy while being treated in the adjuvant setting. The median ACNU starting dose was 25 mg/m 2 (range, 20-30 mg/m 2 ; 3- to 5-wk intervals, 1-8 administrations). The median overall survival in the primary and adjuvant settings was 120 days (median progression-free survival [PFS], 63 days) and 400 days (median PFS, 212 days), respectively. Neutropenia was observed in eight cases (grade 1, n = 1; grade 2, n = 2; grade 3, n = 2; grade 4, n = 3) with nadir neutrophil count at 1 wk after ACNU administration. Mild gastrointestinal toxicity (grade 1-2) was observed in three cases. ACNU was well tolerated and showed a similar outcome to that seen for lomustine, which is a drug commonly used to treat canine HS, in terms of overall survival and PFS in the current study population. Further investigations will need to be undertaken to definitively determine if ACNU is an appropriate alternative to lomustine for the treatment of HS.

T-cell large granular lymphocytic leukemia (T-cell LGLL) is the most common presentation of chronic lymphocytic leukemia (CLL) in dogs. Aleukemic or subleukemic leukemia is a particularly rare variation in both humans and dogs, where bone marrow proliferation is either not or only sparsely translated in the peripheral blood. Neutropenia is a prominent feature in cases of human T-cell LGLL but is normally absent in canine CLL. This report describes a case of a dog presented with an almost 3-year history of asymptomatic neutropenia, lymphopenia, and thrombocytopenia (without anemia). A bone marrow examination, the exclusion of infectious diseases, and clonality testing led to the diagnosis of subleukemic LGLL that responded well to therapy (death occurred 2.5 years later due to an unrelated cause)., (© 2019 American Society for Veterinary Clinical Pathology.)

The efficacy and toxicity of lomustine and prednisone for treating high-grade completely excised mast cell tumors (MCTs) was evaluated in a retrospective study of 15 dogs. Dogs were treated with lomustine (CCNU) at 70 mg/m 2 every 4 weeks and prednisone at 0.5 to 1 mg/kg body weight PO daily. Eight dogs had treatment failures due to recurrence at the site of the initial surgery (2/15), de novo cutaneous MCT (4/15), or metastatic disease (2/15). The median overall survival time was 904 days, with 9 dogs alive at 1 year and 6 dogs alive after 2 years. All but 2 of the dogs had toxicity throughout their treatment protocol, with neutropenia (67%) and elevations in ALT (60%) being the most common; however, no dogs required hospitalization. The protocol was overall well-tolerated and lomustine/prednisone should be considered in the adjunctive treatment of high-grade mast cell tumors., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

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., (© 2019 John Wiley & Sons Ltd.)

Doxorubicin (DOX) area-under-the-curve (AUC) was calculated for 40 dogs with spontaneously occurring cancers using a previously validated limited-sampling approach. All dogs were administered a dose of 30 mg/m 2 by intravenous infusion and serum samples were collected at 5, 45 and 60 minutes post-infusion. DOX and its major metabolite, doxorubicinol (doxol), were quantified in serum samples using high-performance liquid chromatography tandem-mass spectrometry. Wide interpatient variability was observed in the predicted DOX AUC with a coefficient of variation of 34%. A significant relationship was found between DOX AUC and absolute white blood cell count (P = 0.003), absolute neutrophil count (ANC; P = 0.002) and surviving fraction of neutrophils (P = 0.03) approximately 1 week after dosing (nadir). No changes in other hematologic parameters (red blood cells, platelets, lymphocytes, haemoglobin) were found to correlate with DOX AUC. The absolute dose (mg) and the dose per unit body weight (mg/kg) were not significantly correlated with nadir ANC. No relationships were found between maximum serum doxol concentration and myelosuppression. Baseline ANC was also significantly correlated to nadir ANC and a model was constructed using baseline ANC and DOX AUC that significantly described the nadir ANC. These findings demonstrate the important relationship between systemic DOX exposure and degree of neutropenia in dogs, and suggest a potential for individualized, pharmacokinetically-guided DOX dosing in dogs., (© 2019 John Wiley & Sons Ltd.)

Combination chemotherapy can be an effective option for treating resistant lymphoma in dogs. This retrospective study examined the tolerability and efficacy of the combination of 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (dacarbazine) (DTIC) in a population of dogs with lymphoma resistant to a doxorubicin-containing chemotherapy protocol. Mitoxantrone was administered at 5 mg/m 2 IV over 10 min followed by DTIC at 600 mg/m 2 IV over 5 hr, every 3 wk. All dogs were treated with prophylactic trimethoprim-sulfadiazine and metoclopramide. The frequency of grade 4 neutropenia was 18%, and 5% of dogs were hospitalized from sepsis. Gastrointestinal toxicity was uncommon. The overall response rate was 34% (15 of 44; 95% confidence interval 20-48%) for a median duration of 97 days (range 24-636 days, 95% confidence interval 44-150 days). Fourteen of 15 dogs who received mitoxantrone and DTIC as first rescue responded to treatment. Dogs who achieved complete remission to their initial L-asparaginase, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy protocol were more likely to respond to mitoxantrone and DTIC (23 versus 11%, P = .035). The combination of mitoxantrone and DTIC is a safe treatment option for resistant lymphoma in dogs.

A 10 yr old spayed female toy poodle was presented to a tertiary referral center for a 10 day history of waxing and waning lethargy, vomiting, diarrhea, and anorexia. An immune-mediated neutropenia (IMN) was suspected to be the underlying cause of her clinical signs. A bone marrow aspirate was obtained from the chostochondral junction of the 11th and 12th ribs on the right side and provided a definitive diagnosis of IMN. A positive response to therapy and repeat blood work further confirmed the diagnosis. Obtaining bone marrow aspirates from the chostochondral junction is a safe, cheap, and reliable method of diagnosing IMN and can be performed in the private practice setting with light sedation and minimal need for specialized equipment.

5-Fluorouracil (5-FU) is used in combination chemotherapy protocols for human head and neck cancer and other epithelial neoplasms. However, a paucity of literature describing use of this drug in veterinary oncology exists, likely due to previous reports of fatal neurotoxicity in both dogs and cats, mainly due to ingestion of human creams. The primary aim of this retrospective study was to report the safety of concurrent 5-FU and carboplatin in canine carcinomas. Secondarily, we aimed to look at the efficacy of the combination using overall response rate in treated dogs. Medical records were searched from 2007 to 2017 for dogs treated with both agents; 24 dogs met inclusion criteria. Carboplatin dosages ranged from 180 to 250 mg/m 2 (median 200 mg/m 2 ); 5-FU dosage was 150 mg/m 2 . Fourteen dogs had myelosuppression, ranging from Grade I to asymptomatic Grade IV; thrombocytopenia was more common than neutropenia. Gastrointestinal upset was uncommon, with only seven dogs having Grade I or II nausea, vomiting or diarrhoea. No cases were hospitalized for any of the above toxicities. One dog had an episode of ataxia, which could not be differentiated between otitis and 5-FU neurotoxicity. This protocol is well tolerated. Response rate in the gross disease setting was 43% (three complete responses, three partial responses). Prospective analysis of this combination protocol, and potentially 5-FU with other platinum agents, is warranted in the treatment of canine carcinomas., (© 2018 John Wiley & Sons Ltd.)

Cyclophosphamide is an alkylating agent used as chemotherapy for cats with lymphoma, carcinomas and sarcomas. Clinical and pharmacokinetic studies of cyclophosphamide in normal and tumor-bearing cats have shown minimal toxicity and cyclophosphamide at clinically used dosages rarely requires dosage adjustment or treatment delays. Dose intensity appears important for treatment of most cancers; the aim of this study was to perform a modified dose escalation study of cyclophosphamide to establish the maximally tolerated dosage (MTD) for intravenous cyclophosphamide in cats. The dose limiting toxicity appeared to be neutropenia, and 30% of cats experienced grade 3 or grade 4 neutropenia at a cyclophosphamide dosage of 480mg/m 2 , which was determined as the MTD. Delayed neutropenia was observed commonly at higher dosages. Thrombocytopenia was less common than neutropenia, and always transient. Gastrointestinal toxicities were uncommon even at MTD. The recommended dosage for single agent cyclophosphamide in cats is 460mg/m 2 with a post-treatment interval of three weeks, with hematology performed before any subsequent chemotherapy is administered. This dosage appears safe in combination with prednisolone and l-asparaginase; but has not been evaluated in combination with other chemotherapy agents, or with a post-treatment interval shorter than 3 weeks. Such combinations and shorter intervals are found in some protocols, so this recommended cyclophosphamide dose cannot be considered a direct substitute for cyclophosphamide dosages in existing protocols. There is a suggestion that inadequate renal function may exacerbate the myelosuppression of cyclophosphamide which should be further evaluated., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Thirty-seven dogs with histologically or cytologically confirmed malignant tumors treated with single-agent mitoxantrone at 5 mg/m 2 were evaluated in a retrospective study assessing the correlation between body weight and neutropenia associated with a single dose of mitoxantrone in dogs. Overall, eight dogs (21%) experienced grade 3 neutropenia and five dogs (14%) experienced grade 4 neutropenia on day 7 following mitoxantrone chemotherapy. Dogs ≤10 kg body weight were significantly more likely to develop grade 3 or 4 neutropenia (5.8 relative risk; 95% confidence interval, 2.6-12.9; P < .0001) than dogs >10 kg. Dogs ≤15 kg body weight were significantly more likely to develop grade 3 or 4 neutropenia (8.1 relative risk; 95% confidence interval, 2.1-31.3; P < .0001) than dogs >15 kg. Of the 13 patients who developed grade 3 or 4 neutropenia, 6 (46%) were hospitalized for clinical signs related to neutropenia. Based on the severity of neutropenia and the resulting hospitalization seen in dogs ≤10 kg, a dose reduction could be considered for the initial dose of mitoxantrone, and clinicians should be aware of the increased risk of neutropenia in patients 10.1 to ≤15 kg.

A 4-year-old, unilateral cryptorchid golden retriever dog was presented to the Ontario Veterinary College Health Sciences Centre with gynecomastia, dribbling urine, lethargy, neutropenia, and thrombocytopenia. A Sertoli cell tumor was diagnosed in a cryptorchid testicle with estrogen-induced myelotoxicity. The tumor was removed and bone marrow regenerated within 4 months.

Background: Prechemotherapy absolute neutrophil count (ANC) cutoffs are arbitrary and vary across institutions and clinicians. Similarly, subjective guidelines are utilized for the administration of prophylactic antibiotics in neutropenic dogs., Objectives: To evaluate the impact of various ANC cutoffs on chemotherapy administration in dogs with lymphoma treated with CHOP chemotherapy and to determine whether an association between prechemotherapy ANC and subsequent toxicity exists. The secondary objective was to evaluate a currently used ANC cutoff to indicate prescription of prophylactic antibiotics., Animals: Dogs diagnosed with lymphoma treated with CHOP chemotherapy (n = 64)., Methods: Six hundred and fifteen ANCs were stratified into 6 classes. The 3 ANC cutoffs 1.5 × 10 3 /μL, 2.0 × 10 3 /μL, and 2.5 × 10 3 /μL were assessed. The presence of an association between prechemotherapy ANC class and toxicity was determined. Afebrile neutropenic dogs with ANC <1.5 × 10 3 /μL but above the criteria for prophylactic antibiotics were evaluated., Results: Chemotherapy was not administered in 7% of visits with an ANC cutoff of 1.5 × 10 3 /μL; chemotherapy would not have been administered in 10% and 16% of visits with an ANC cutoff of 2.0 × 10 3 /μL or 2.5 × 10 3 /μL, respectively. There was no association among the 3 lower prechemotherapy ANC classes and toxicity. All dogs with ANC 0.75-1.5 × 10 3 /μL recovered spontaneously without medical intervention., Conclusion and Clinical Importance: The number of dose delays was minimized with a prechemotherapy ANC cutoff of 1.5 × 10 3 /μL, and the prechemotherapy ANC class 1.5-1.99 × 10 3 /μL was not associated with an increased toxicity. Further investigation of an ANC cutoff near 0.75 × 10 3 /μL in which to prescribe prophylactic antibiotics is indicated., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Combination chemotherapy holds promise for improving outcomes in malignancy when compared with single-agent approaches. Care must be taken to avoid overlapping toxicity and to utilize agents with differing mechanisms of action. A phase I dose-finding trial was performed to determine the maximally tolerated dose (MTD) of a concurrent toceranib and doxorubicin (DOX) combination protocol where toceranib dose was maintained at or near 2.75 mg kg -1 by mouth every other day (PO EOD) while escalating DOX dosage. The dose-limiting toxicity was found to be neutropenia and the MTD of the combination was determined to be 25 mg m -2 of DOX q 21 days given concurrently with toceranib 2.75 mg kg -1 PO EOD. This combination was well tolerated with no excessive gastrointestinal toxicity nor novel adverse events (AEs) noted. Anti-tumour activity was observed in the majority of cases. This combination warrants further investigation in the context of phase II/III clinical trials to characterize efficacy and long-term AE profiles., (© 2016 John Wiley & Sons Ltd.)

The purpose of this study was to describe the toxicity profile of toceranib phosphate in tumour bearing cats. Medical records were reviewed from seven institutions. Patients with incomplete medical records and those receiving concurrent chemotherapy or NSAIDs (non-steroidal anti-inflammatory) were excluded. Fifty-five cats met the inclusion criteria. Carcinoma was diagnosed in 55% of cases. Median oral toceranib dose was 2.7 mg kg -1 and was most commonly administered on Monday, Wednesday and Friday. Thrombocytopenia (16.3%) and neutropenia (9.1%) were the most common haematologic toxicities. Azotemia (14.5%) and alanine aminotransferase (ALT) elevations (7.2%) were the most frequently encountered biochemical alterations. Gastrointestinal (GI) toxicity was seen in 21.8% of cats, and was lower than previously reported in dogs. The results of this study showed that treatment of cats with toceranib is well-tolerated and toxicity is uncommon. Additional studies to define a more structured dosing schedule and to evaluate the efficacy of toceranib in the treatment of feline cancers are needed., (© 2016 John Wiley & Sons Ltd.)

An adult female spayed dog was evaluated after inadvertently receiving a total dose of 1,750 mg oral cyclophosphamide, equivalent to 2,303 mg/m 2 , over 21 days (days -21 to 0). Nine days after the last dose of cyclophosphamide (day +9), the dog was evaluated at Perth Veterinary Specialists. Physical examination revealed mucosal pallor, a grade 2/6 systolic heart murmur, and severe hemorrhagic cystitis. Severe nonregenerative pancytopenia was detected on hematology. Broad spectrum antibiotics, two fresh whole blood transfusions, granulocyte colony stimulating factor, and tranexamic acid were administered. Five days after presentation (day +14), the peripheral neutrophil count had recovered, and by 12 days (day +21) the complete blood count was near normal. A second episode of thrombocytopenia (day +51) was managed with vincristine, prednisolone, and melatonin. The dog made a complete recovery with no long-term complications at the time of writing. To the author's knowledge, this is the highest inadvertently administered dose of cyclophosphamide to result in complete recovery.

Objectives: To describe, in a cohort of dogs with presumed primary immune-mediated neutropenia, the presenting clinical characteristics, haematology results, bone marrow characteristics, therapies used (drugs and doses), clinical response to treatment, relapse and outcome at six months and one year., Methods: Multi-institutional recruited retrospective descriptive case series with voluntary submissions. Presumed immune-mediated neutropenia was diagnosed based on a neutrophil concentration <1·5×10 9 cells/L on a minimum of two complete blood counts, exclusion of other causes of neutropenia based on a diagnostic bone marrow aspirate or biopsy, and exclusion of secondary immune-mediated neutropenia. Dogs meeting these diagnostic criteria between 2006 and 2013, and that had a haematocrit of ≥29% and minimum of two complete blood clounts performed after initiation of therapy, were included., Results: Information on 35 dogs was included. Neutropenia was less than 0·5×10 9 cells/L in most cases (21 dogs), 0·5 to ·99×10 9 cells/L in 11, and 1.0 to 1·49×10 9 cells/L in three. Eight dogs had thrombocytopenia, which was severe (<49·9×10 9 cells/L) in three. [Correction added on 23 May 2017, after first online publication: the cell numbers were incorrect due to errors in the conversion of cell measurements to international units. The numbers have been corrected throughout the article and Table 2.] Twenty-three dogs had myeloid hyperplasia, 10 dogs had myeloid hypoplasia and two dogs had normal myelopoiesis. Neutropenia resolved in 32 of 33 dogs within two weeks of starting corticosteroid therapy and in all dogs within one month. Relapse of neutropenia occurred in 12 cases within one year., Clinical Significance: Initial response of presumed primary immune-mediated neutropenia cases to corticosteroid therapy can be excellent. Long-term monitoring for relapse is warranted because 34% of cases relapsed during or after taper of immunosuppressive medications., (© 2017 British Small Animal Veterinary Association.)

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., (© 2015 John Wiley & Sons Ltd.)

The purpose of this study was to determine the plasma pharmacokinetics (PK) and toxicity of zebularine, an oral cytidine analog with demethylating activity, in dogs. Plasma zebularine concentrations were determined by HPLC-MS/MS following an oral zebularine dose of 8 or 4 mg kg -1 . Plasma zebularine clearance was constant. Mean maximum concentration (C max ) was 23 ± 4.8 and 8.6 ± 1.4 µM following 8 and 4 mg kg -1 , respectively. Mean half-life was 5.7 ± 0.84 and 7.1 ± 2.1 following 8 and 4 mg kg -1 , respectively. A single 8 mg kg -1 dose was well tolerated. Daily 4 mg kg -1 treatment in three laboratory dogs resulted in grade 4 neutropenia (n = 3), grade 1 anorexia (n = 2) and grade 1 or 2 dermatologic changes (n = 2). All adverse events resolved with supportive care. A 4 mg kg -1 dose every 21 days was well tolerated. A follow-up dose escalation study is in progress with a lower starting dose., (© 2015 John Wiley & Sons Ltd.)

An 8-year-old spayed Portuguese water dog was presented with dysuria, lethargy, and anorexia. A profound neutropenia and pancytopenia were identified. Bone marrow aspirates revealed neutrophilic hyperplasia, a significant left shift, and toxic changes, suggesting immune-mediated destruction as a likely underlying mechanism. Immunosuppressive therapy was instituted and clinical signs improved.

Objective: The aim of this retrospective study was to evaluate frequency, prognostic factors, and differences for various etiologies of neutropenia in dogs., Material and Methods: A total of 391 dogs with neutrophil counts < 2.78 x 10 9 /l (January 2008 to December 2012) were included and, depending on the etiology of neutropenia, assigned to seven diagnostic groups: nonbacterial infectious disease, increased demand due to marked inflammation, drug-associated, bone-marrow diseases, immune-mediated, physiologic, miscellaneous. Absolute neutrophil counts, evidence of neutrophil toxicity or left shift, case history, rectal temperature, hospitalization, and survival were compared among groups., Results: Increased demand due to marked inflammation (90/391, 23%) and nonbacterial infectious disease (70/391, 18%) were the most common causes for neutropenia, followed by drug-associated neutropenia (43/391, 11%) and bone-marrow disease (32/391, 8%). Immune-mediated and physiologic neutropenia (both 16/391, 4%) were uncommon. Almost one third (124/391, 32%) of dogs were assigned to the miscellaneous group. Absolute neutrophil counts were significantly higher (p < 0.01) in dogs of the physiologic and miscellaneous groups than in the other groups. Dogs with immune-mediated neutropenia or nonbacterial infectious disease displayed significantly lower absolute neutrophil counts than dogs with neutropenia due to an increased demand (p < 0.001) and were most commonly referred with a history of fever (11/16, 69%) or gastrointestinal signs (52/70, 74%), respectively. Neutrophil toxicity and left shift were most commonly associated with an increased demand due to marked inflammation (60/90 and 25/90, 67% and 28%, respectively) and the mortality rate was highest in this group (32/90, 36%)., Conclusion: Neutrophil toxicity and left shift are associated with an increased demand due to marked inflammation and may indicate a poor prognosis. The lower the absolute neutrophil count, the greater the probability of an immune-mediated neutropenia., Clinical Relevance: Neutropenia should be assessed in context with case history, clinical examination, and neutrophil morphology.

Background: Compounded lomustine is used commonly in veterinary patients. However, the potential variability in these formulations is unknown and concern exists that compounded formulations of drugs may differ in potency from Food and Drug Administration (FDA)-approved products., Hypothesis/objectives: The initial objective of this study was to evaluate the frequency and severity of neutropenia in dogs treated with compounded or FDA-approved formulations of lomustine. Subsequent analyses aimed to determine the potency of lomustine obtained from several compounding pharmacies., Animals: Thirty-seven dogs treated with FDA-approved or compounded lomustine., Methods: Dogs that received compounded or FDA-approved lomustine and had pretreatment and nadir CBCs performed were eligible for inclusion. Variables assessed included lomustine dose, neutrophil counts, and severity of neutropenia. Lomustine 5 mg capsules from 5 compounding sources were tested for potency using high-pressure liquid chromatography (HPLC) with ultraviolet (UV) detection., Results: Twenty-one dogs received FDA-approved lomustine and 16 dogs were treated with lomustine prescribed from a single compounding pharmacy. All dogs treated with FDA-approved lomustine were neutropenic after treatment; 15 dogs (71%) developed grade 3 or higher neutropenia. Four dogs (25%) given compounded lomustine became neutropenic, with 2 dogs (12.5%) developing grade 3 neutropenia. The potency of lomustine from 5 compounding pharmacies ranged from 50 to 115% of the labeled concentration, with 1 sample within ±10% of the labeled concentration., Conclusions and Clinical Importance: These data support broader investigation into the potency and consistency of compounded chemotherapy drugs and highlight the potential need for greater oversight of these products., (Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)