Hemorrhagic diathesis and bone marrow aplasia secondary to lomustine overdose in a dog

Abstract

A 9-year-old mixed breed 13 kg spayed female dog was referred for evaluation of two masses in the right abdominal mammary gland region. A firm, multilobular, well-demarcated, 2.0 × 3.0 × 1.5 cm nodule was observed in the right caudal abdominal mammary gland. In addition, a firm, well-demarcated, 2.0 × 1.2 × 1.0 cm skin nodule was present between the right cranial and the caudal abdominal mammary glands.The dog's body condition was good, and the vital signs were normal. Thoracic radiography, CBC (Table 1), and partial serum biochemical panel were unremarkable. Radical right unilateral mastectomy was elected, and the excised mammary tissue, nodules, and right inguinal lymph node were submitted for histologic evaluation. Histologic examination revealed a circumscribed and encapsulated grade I complex mammary gland carcinoma in the caudal abdominal mammary gland with clear surgical margins. The cutaneous mass between the cranial and caudal abdominal mammary glands was diagnosed as a mast cell tumor, which was classified as high grade or grade III, according to the Kiupel 1 and Patnaik 2 grading systems, respectively (close surgical margins). Additionally, neoplastic mast cell infiltrates were noted in the nodal parenchyma of the right inguinal lymph node. The dog was re-examined 47 days postoperatively, and the surgical scar did not show visible local mast cell tumor or mammary gland mixed Abstract A 9-year-old mixed breed 13 kg spayed female dog was presented for evaluation of two masses in the right abdominal mammary gland region. Surgery was conducted to excise the masses. A grade I complex mammary gland carcinoma and high grade (grade III) mast cell tumor with an inguinal lymph node metastasis were diagnosed. Forty-seven days after the surgical procedure, the mast cell tumor relapsed, and neoadjuvant treatment with lomustine (81 mg/m 2 ) was prescribed. Thirteen days from initiation of lomustine therapy, the dog was re-presented to the hospital with bloody diarrhea, hematemesis, epistaxis, an elevated rectal temperature, depression, severe dehydration, and marked dyspnea. The CBC showed severe thrombocytopenia and leukopenia. According to the owner, lomustine (45mg per os [PO]) was mistakenly administered daily for 10 consecutive days (total dose, 810 mg/m 2 ). The dog died and a necropsy was performed. The main gross lesions consisted of severe multifocal hemorrhages in multiple organs, especially in the digestive system. Histopathologic evaluation revealed disseminated hemorrhages, as well as marked bone marrow aplasia. This report describes the clinical, hematologic, gross, and histologic findings in a fatal case of lomustine overdose in a dog. K E Y W O R D S canine, chemotherapy, leukopenia, myelotoxicity, neutropenia, thrombocytopenia How to cite this article: Henker LC, Kemper RT, Bianchi SP, Bandinelli MB, Pavarini SP. Hemorrhagic diathesis and bone marrow aplasia secondary to lomustine overdose in a dog. Vet Clin Pathol. 2019;48:255-258. https://doi.

A Retrospective Evaluation of Chemotherapy Overdoses in Dogs and Cats

“…Chemotherapy OD rates in veterinary medicine are similarly unknown and current literature is based on individual case reports. Dog chemotherapy ODs have been reported with cyclophosphamide ( 16 , 17 ), 5-fluorouracil ( 18 ), lomustine ( 19 ), methotrexate ( 20 , 21 ), vincristine ( 22 ) and doxorubicin ( 23 ). Cat chemotherapy ODs have been reported with vinca alkaloids ( 24 , 25 ).…”

Use of eltrombopag and granulocyte colony‐stimulating factor in treatment of lomustine overdose in a dog

“…15 While there are few reports of lomustine overdose in the veterinary literature, one report of a fatal overdose in a dog (total dose 810 mg/m 2 ) documents severe diffuse haemorrhagic diathesis secondary to bone marrow aplasia and thrombocytopenia. 16 Reports of overdose in the human literature document prolonged myelosuppression from 10 to 20 days post-overdose. This is an early onset of the signs considering that the nadir is expected to be noted at 4-5 weeks post-administration.…”

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

“… 1 Inaccurate chemotherapy administration also occurs in veterinary medicine, despite the adoption of similar safety protocols. 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 Reports regarding the frequency and type of ODs are lacking in both human and veterinary medicine.…”