ABSTRACT
OBJECTIVE: To study the pharmacokinetic profiles of intravenous busulfan in Chinese pediatric and adult patients undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT). METHODS: Blood samples of 22 pediatric and 9 adult patients were collected following the last dose of a 3-4 d, 12-16 doses intravenous busulfan regimen in children with thalassemia and adult leukemia patients or of a 4 d, once-daily intravenous busulfan regimen in pediatric hematologic malignancies patients. The plasma concentrations of busulfan were determined by LC/MS/MS, and the pharmacokinetic parameters of busulfan were calculated by DAS. RESULTS: The plasma concentration-time curves after the last dose intravenous busulfan in 31 patients were fitted to a two-compartment model. The main pharmacokinetic parameters in pediatric and adult patients undergoing allo-HSCT were as follow: CL(0.4±0.2) and(0.2±0.1) L·h-1·kg-1, t1/2β(3.3±1.5) and(3.1±0.8) h, Vd(0.6±0.8) and(0.4±0.2) L·kg-1, and Cav(590.4±265.3) and(572.2±214.7) μg·L-1, respectively. The CL after intravenous administration of busulfan was different between pediatric and adult patients(P<0.05). The t1/2β, Vd, CL, K10, and K12 were significantly different(P<0.01) between the pediatric patients with thalassemia and hematologic malignancies. CONCLUSION: The inter- and intra-patient variabilities in the main pharmacokinetic parameters of intravenous busulfan in children and adults are statistically significant. The difference of pharmacokinetic parameters between children with different diseases is obvious. The t1/2β and Vd in pediatric patients with thalassemia have significant reduction. More research is warranted on intravenous busulfan pharmacokinetics in Chinese patients, and therapeutic drug monitoring and appropriate dose adjustment are recommended.
ABSTRACT
BACKGROUND: The use of non-myeloablative stem cell transplantation (NST) has recently been increasing for treating the patients who cannot tolerate ablative hematopoietic stem cell transplantation (HSCT). Although graft-versus-host disease (GVHD) is one of the greatest problems in HSCT, the clinical effect of GVHD following NST is not clear. We undertook this study to evaluate the clinical manifestations of GVHD and the outcomes after NST. METHODS: From October 2000 to October 2004, 61 patients underwent NST with a fludarabine-based conditioning regimen. The cumulative incidence of GVHD and the survival rates were obtained from the Kaplan-Meier curves. RESULTS: With a median follow-up of 195 days, the estimate for overall three-year survival was 32%. The cumulative incidences of grades II~IV acute GVHD and chronic GVHD were 33% (18/53) and 78% (29/37), respectively. The response rates for acute and chronic GVHD were 33% and 89%, respectively. The survival rates of patients with acute and chronic GVHD were 27% and 89%, respectively. The median survival time was 6.5 months CONCLUSION: The incidence of GVHD after NST did not differ from that after ablative HSCT. This study suggests that the aggressive treatment of acute GVHD should be considered to improve the overall survival after NST.