RESUMO
Treosulfan is given off-label in pediatric allogeneic hematopoietic stem cell transplant. This study investigated treosulfan's pharmacokinetics (PKs), efficacy, and safety in a prospective trial. Pediatric patients (n = 87) receiving treosulfan-fludarabine conditioning were followed for at least 1 year posttransplant. PKs were described with a two-compartment model. During follow-up, 11 of 87 patients died and 12 of 87 patients had low engraftment (≤ 20% myeloid chimerism). For each increase in treosulfan area under the curve from zero to infinity (AUC(0-∞) ) of 1,000 mg hour/L the hazard ratio (95% confidence interval) for mortality increase was 1.46 (1.23-1.74), and the hazard ratio for low engraftment was 0.61 (0.36-1.04). A cumulative AUC(0-∞) of 4,800 mg hour/L maximized the probability of success (> 20% engraftment and no mortality) at 82%. Probability of success with AUC(0-∞) between 80% and 125% of this target were 78% and 79%. Measuring PK at the first dose and individualizing the third dose may be required in nonmalignant disease.
Assuntos
Bussulfano/análogos & derivados , Transplante de Células-Tronco Hematopoéticas , Agonistas Mieloablativos/farmacocinética , Condicionamento Pré-Transplante , Adolescente , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Bussulfano/farmacocinética , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Esquema de Medicação , Monitoramento de Medicamentos , Inglaterra , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Lactente , Recém-Nascido , Infusões Intravenosas , Masculino , Modelos Biológicos , Agonistas Mieloablativos/administração & dosagem , Agonistas Mieloablativos/efeitos adversos , Estudos Prospectivos , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/análogos & derivadosRESUMO
A single-center experience of catheter-related blood stream infections in children undergoing hematopoietic stem cell transplant for primary immunodeficiency is described. The rate of definite central venous catheter infections was 5.31/1000 line days. Staphylococcus epidermidis was the most commonly identified organism. Teicoplanin resistance occurred in 17% of S. epidermidis infections. The central catheter was removed in 21% of infections.
