RESUMEN
Bleomycin is generally used as an antineoplastic drug for the intravenous treatment of germ cell tumors or lymphomas. Due to its toxic effect on epithelial cells bleomycin is also used for the treatment of malignant pleural or pericardial effusions. Inadvertent intrathecal administration of cytotoxic drugs may occur due to increasingly complex therapeutic protocols, even when control mechanisms are applied. We report the case of a 39-year-old man with chronic myeloid leukemia. During the treatment of a lymphoblast crisis 30 mg of bleomycin were inadvertently injected intrathecally. Prompt cerebrospinal fluid exchange, dilution with normal saline, and corticosteroid treatment resulted in a positive outcome without major side effects.
Asunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Bleomicina/administración & dosificación , Líquido Cefalorraquídeo/metabolismo , Inyecciones Espinales , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Errores de Medicación , Corticoesteroides/farmacología , Adulto , Antibióticos Antineoplásicos/efectos adversos , Antibióticos Antineoplásicos/líquido cefalorraquídeo , Bleomicina/efectos adversos , Bleomicina/líquido cefalorraquídeo , Encefalomielitis/inducido químicamente , Encefalomielitis/terapia , Humanos , Masculino , Resultado del TratamientoRESUMEN
The neurotoxic effects and cerebrospinal fluid (CSF) pharmacokinetics of bleomycin were evaluated in beagles after chronic intraventricular administration twice a week for 8 consecutive weeks. Bleomycin was reasonably well tolerated at doses of 0.067 to 0.3 mg/week. Doses higher than 0.3 mg/week produced marked elevation of CSF protein levels and a necrotizing vasculitis within the central nervous system. Pharmacokinetic studies were performed approximately 1 month after the completion of the toxicity studies. [3H]inulin was used as a reference compound. Both [3H]inulin and bleomycin were cleared from the CSF more slowly than in previous studies and more slowly than in normal dogs, which suggests that bulk CSF absorption was reduced by the drug, probably secondary to protein-induced blockage of the arachnoid granulations through which CSF is normally absorbed. Because a "minimally toxic" dose of bleomycin (approximately 0.1 mg/week) produces a CSF C X t of only 1.9 mg/min/ml, we believe that a Phase I clinical trial would be too dangerous given the limited therapeutic potential that a dose of 0.1 mg/week could achieve.