Ethanol intoxication in paediatric patients receiving intravenous etoposide as conditioning regimen for allogenic hematopoietic stem cell transplant

IntroductionTotal body irradiation associated with etoposide is widely used in conditioning regimens before hematologic stem cell transplantation (HSCT). The etoposide formulation exposes children to a high dose of ethanol, and data on its side effects are scarce. We investigated whether paediatric patients with acute lymphoid leukaemia and lymphoblastic lymphoma were experiencing hypersensitivity reactions or ethanol-related reactions after etoposide infusion before HSCT.MethodsThis study retrospectively analyzed all patients treated with a TBI 12 Gy-based-conditioning associated with etoposide 60 mg/kg before HSCT. Hypersensitivity reactions (tachycardia, hypotension, dyspnea, flushing and erythema) were opposed to ethanol-related symptoms (dizziness, impaired balance) in patients who presented clinical reactions during or after etoposide infusion. Ethanol-induced toxicity risk factors related to demographics and infusion data were analysed such as age, gender, etoposide and ethanol amount, etoposide or ethanol infusion rate.ResultsBetween January 2015 and December 2020, 62 patients received etoposide as conditioning regimen and 48 patients were included in the study. The median etoposide dose was 1960 mg (414-3600), and the median amount of ethanol in the preparation was 24.3 g (5.1-44.6). Twenty patients exhibited etoposide-related symptoms. Eighteen patients presented ethanol-related symptoms, and 2 patients had hypersensitivity reactions and were admitted to the Intensive Care Unit. The incidence of ethanol-related symptoms was significantly higher in patients ≥ 7.5 years old at the time of HSCT (<i>p</i> = 0.04). No other risk factors were found.ConclusionThese data must raise awareness among physicians and pharmacists about the high dose of ethanol to which children are exposed during conditioning, and their adverse effects.