Tyrosine kinase inhibitors (TKIs) have dramatically changed the survival of chronic myeloid leukemia (CML) patients, and treatment-free remission (TFR) has recently emerged as a new goal of CML treatment. The aim of this work was to develop recommendations for TKI discontinuation in Latin America (LA), outside of clinical trials. A working group of CML experts from LA discussed 22 questions regarding TFR and reached a consensus for TFR recommendations in the region. TFR is indicated in patients in first chronic phase, with typical BCR-ABL transcripts, under TKI treatment of a minimum of 5 years, in sustained deep molecular response (DMR; molecular response 4.5 [MR4.5]) for 2 years. Sustained DMR must be demonstrated on at least 4 international reporting scale quantitative polymerase chain reaction (PCR) tests, separated by at least 3 months, in the immediate prior 2 years. After second-line therapy, TFR is indicated in previously intolerant, not resistant, patients. Molecular monitoring is recommended monthly for the first 6 months, every 2 to 3 months from months 7 to 12, and every 3 months during the second year, indefinitely. Treatment should be reintroduced if major molecular response is lost. Monitoring of withdrawal syndrome, glucose levels, and lipid profile is recommended after discontinuation. After TKI reintroduction, molecular monitoring is indicated every 2 to 3 months until MR4.0 achievement; later, every 3 to 6 months. For the TFR attempt, having standardized and reliable BCR-ABL PCR tests is mandatory. These recommendations will be useful for safe discontinuation in daily practice and will benefit patients who wish to stop treatment in emergent regions, in particular, with TKI-related chronic adverse events.

This case report describes an episode of acute ataxia, tremor, vertical nystagmus and progressive weakness in a mixed breed dog treated with high doses of metronidazole. Complete blood cell count, serum biochemistry, coagulation profile, blood pressure measurement, urinalysis, computed tomography of the brain and cerebrospinal fluid examination were unremarkable. Metronidazole had been administered at a dose of 65 mg/ kg/day and neurotoxicity was, therefore, suspected. Drug concentrations in the patient's serum and cerebrospinal fluid were measured using high-performance liquid chromatography and compared to control dogs. Metronidazole administration was immediately discontinued; supportive care consisted of fluid therapy and diazepam treatment. The neurological status of the patient improved rapidly within 72 h. The aim of this case report is to describe the clinical presentation of metronidazole intoxication in a mixed breed dog and to interpret the chromatographic analysis which can be a beneficial diagnostic and screening tool in dogs intoxicated with metronidazole.Keywords: vestibular diseases; cerebellar dysfunction; canine diseases; gamma-aminobutyric acid; chromatography Metronidazole (MTZ) is an injectable and oral synthetic, nitroimidazole antibacterial and antiprotozoal agent. It is commonly used in veterinary practice to treat a wide variety of conditions (Watson 1980;Tams 1984;Happonen et al. 2000;Olson et al. 2005;Cattin et al. 2008;Jergens et al. 2010;Senhorinho et al. 2012). The mode of action requires strict anaerobic conditions; susceptible infectious agents include Bacteroides sp., Clostridium sp., Giardia sp. etc. (Rossignol et al. 1984;Even et al. 1998; Plumb 1999;Marks and Kather 2003;Hausen et al. 2011). MTZ is primarily metabolised in the liver and crosses the blood-brain barrier rapidly; in mice, the unaltered drug accumulates in the cerebellum and hippocampal areas (Plumb 1999;Olson et al. 2005). The recommended dosage for long-term treatment in dogs is 10 mg/kg p.o. twice or three times a day (Plumb 1999). Adverse effects include neurological disorders, lethargy, weakness, neutropenia, hepatotoxicity, haematuria, nausea, vomiting and diarrhoea (Plumb 1999;Weiss 2005). MTZ toxicity can develop suddenly and if unrecognised, can lead to rapid deterioration and death (Wright and Tyler 2003). In cases of acute toxicity from a chronic overdose in dogs, the drug should be discontinued and the patients treated supportively and symptomatically (Wright and Tyler 2003). The aim of this case report is to describe a metronidazole-induced neurotoxicity with subsequent chromatographic analysis in a dog. Case descriptionA six and a half-year-old 7.2-kg uncastrated male mixed breed dog was presented for neurological exSupported by the Ministry of Education, Youth and Sports of the Czech Republic (Institutional research development).

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Introducción y objetivos. La anemia aplásica se define como pancitopenia asociada a hipocelularidad de la médula ósea en ausencia de cambios displásicos y fibrosis. El 70%-80% de casos adquiridos son idiopáticos y los restantes son secundarios a medicamentos, infecciones u otras patologías. El eltrombopag, aprobado en 2014 por la FDA para su tratamiento, estimula no solo la trombopoyesis, sino también la eritropoyesis y granulopoyesis. Se describe la respuesta al tratamiento con eltrombopag de dos pacientes con anemia aplásica adquirida.