Filgrastim Use in the Treatment of Azathioprine-Induced Myelosuppression Toxicity After Prescription Error in the Feline.

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.

A canine case of Ehrlichia canis infection without a history of being in an endemic area in Japan.

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 in 65 dogs (2005-2023).

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.

Large T-cell extradural lymphoma with concurrent marked cerebrospinal fluid eosinophilia in a dog.

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.

Individualized chemotherapy drug dose escalation in dogs with multicentric lymphoma.

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/m2 or higher in 11 dogs, cyclophosphamide to 300 mg/m2 or higher in 16 dogs, and doxorubicin to 35 mg/m2 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.

A retrospective evaluation of phenobarbital-induced hematologic changes in 69 cats.

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.

D-penicillamine-associated neutropenia in a Doberman pinscher.

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.

Neutropénie associée à la D-pénicillamine chez un Doberman pinscher. L'hépatite associée au cuivre chez le chien résulte de niveaux élevés de cuivre secondaires à une augmentation de l'apport ou à une diminution de la clairance. Le traitement consiste à établir un bilan négatif du cuivre et peut inclure une thérapie par chélation. Traditionnellement, la thérapie par chélation chez le chien utilise la D-pénicillamine, dont il a été démontré qu'elle a de graves effets secondaires chez l'homme. Les effets secondaires n'ont pas été bien documentés chez les chiens, mais peuvent inclure une néphrotoxicité et des réactions dermatologiques. Cet article est le premier à rapporter une neutropénie chez un chien secondaire à un traitement par chélation utilisant la D-pénicillamine. Dans ce cas, une numération globulaire complète (CBC) recueillie avant le début du traitement par chélation était normale et une neutropénie a été documentée 4 mois après le début du traitement. Un examen cytologique de la moelle osseuse a confirmé une hypoplasie myéloïde. Après l'arrêt de la D-pénicillamine, la neutropénie a disparu. Sur la base de ce rapport de cas, des vérifications périodiques de la CBC après le début du traitement par chélation de la D-pénicillamine sont recommandées pour guider les décisions de traitement.Message clinique clé :Les chiens atteints d'hépatite associée au cuivre confirmée doivent être traités avec prudence avec de la D-pénicillamine pour le traitement par chélation. La D-pénicillamine peut affecter négativement la moelle osseuse, provoquant une leucopénie caractérisée par une neutropénie. Il est recommandé aux cliniciens de surveiller périodiquement le nombre de neutrophiles lors du traitement des chiens avec de la D-pénicillamine.(Traduit par Dr Serge Messier).

Prevalence of Babesia and Ehrlichia in owned dogs with suspected tick-borne infection in Hong Kong, and risk factors associated with Babesia gibsoni.

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.

A comparison of the Sepsis-2 and Sepsis-3 definitions for assessment of mortality risk in dogs with parvovirus.

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.

Multiorgan neutrophilic inflammation in a Border Collie with "trapped" neutrophil syndrome.

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.

Cyclic hematopoiesis in a mixed-breed dog: case report and brief review.

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 ß-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.

Evaluation of adverse events in small-breed dogs treated with maropitant and a single dose of doxorubicin.

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/m2 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/m2 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/m2 DOX followed by maropitant treatment in 5 to 10 kg dogs; however, additional supportive care might be needed for dogs with inappetence and neutropenia.

Risk factors associated with the onset of lomustine-induced neutropenia in tumour-bearing dogs.

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/m2 (range 27.7-84.9 mg/m2 ). 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/m2 , 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/m2 , 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.

Toxicity, outcome, and management of anthracycline overdoses in 16 dogs.

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.

Transient thrombocytopenia in a cat following G-CSF treatment.

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.

EFFICACY OF HUMAN RECOMBINANT GRANULOCYTE COLONY-STIMULATING FACTOR (G-CSF, FILGRASTIM; NEUPOGEN®) IN NEUTROPENIC CETACEANS.

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.

Neutropenia in dogs receiving vincristine for treatment of presumptive immune-mediated thrombocytopenia.

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.

Biodynamic signatures from ex vivo bone marrow aspirates are associated with chemotherapy-induced neutropenia in cancer-bearing dogs.

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/m2 , 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.

Steroid-responsive neutropenia in a cat with progressive feline leukemia virus infection.

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.

Carboplatin-induced myelosuppression as related to body weight in dogs.

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.