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BONE MARROW TOXICITY INDUCED BY CARMUSTINE (BCNU) IN DOGS

Samantha Ive MIYASHIRO, Mitika Kuribayashi HAGIWARA, Leonardo Pinto BRANDÃO, Sílvia Regina Ricci LUCAS

Carmustine (1,3-bis(2-chloroethyl)-1-nitrosourea; BCNU), a nitrosourea from alkylating agents group, is widely used in human medicine as an antineoplastic agent in the treatment of lymphomas and a variety of other tumors, despite of its cumulative and delayed myelosuppressor effect. Little is known about its use in dogs, specially those aspects related to bone marrow toxicity effect of the drug. Aiming to fullfil this gap, ten healthy dogs were exposed to BCNU (Day 0) in a single dose (50mg/m2) and followed by eight weeks. Physical and hematological examination were made in alternated days and bone marrow aspiration done on days 5 and 55. Biochemical profiles were performed weekly in order to observe any renal or hepatic toxicity of the drug. Leucocyte nadir occured on day 5 to day 9 (850 - 3,600 cells/mm3). Platelet number decreased mildly around day 10 (6,000 - 196,000 platelets/mm3). No red blood cell alteration was observed. Bone toxicity, otherwise human literature, was acute and severe, extremely hypocellular on day 5, with reduction of precursor cells of all series. On day 55, peripheral blood and bone marrow aspects were normal. Only mild increase in serum ALT and ALP activity was observed in three dogs, in spite of no clinical signs. Knowing the drug toxicity, specially hematologic complications which are dose-limiting, a protocol for utilization of this chemotherapic agent in dogs might be established as an alternative one in the treatment of lymphomas.


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