Faraci Maura, Tinelli Carmine, Lanino Edoardo, Giardino Stefano, Leoni Massimiliano, Ferretti Marta, Castagnola Elio, Broglia Monica, De Silvestri Annalisa, Di Martino Daniela, Bartoli Antonella
Hematopoietic Stem Cell Transplant Unit, Department of Hematology-Oncology, Istituto G. Gaslini, Largo G. Gaslini, 5, 16147, Genoa, Italy.
Epidemiology Service, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Eur J Drug Metab Pharmacokinet. 2018 Apr;43(2):173-181. doi: 10.1007/s13318-017-0431-0.
The aim of this report is to describe the experience in the management of busulphan-based conditioning regimen administered before hematopoietic stem cell transplantation (HSCT) in children.
We report the values of the first dose AUC (area under the concentration-time curve, normal target between 3600 and 4800 ng·h/mL) in children treated with oral and intravenous busulphan, and we analyze the impact of some clinical variables in this cohort of patients.
82 children treated with busulphan before HSCT were eligible for the study: 57 received oral busulphan with a mean AUC of 3586 ng·h/mL, while 25 received intravenous busulphan with a mean AUC of 4158 ng·h/mL. Dose adjustment was based on first dose AUC. The dose was increased in 36 children (43.9%) and decreased in 26 patients (31.7%). Age at HSCT (P = 0.015), cumulative dose of busulphan as mg/m (P < 0.001), busulphan dose prescribed as mg/Kg (P = 0.001), intravenous busulphan administration (P < 0.001), type of stem source cells (P = 0.016), and type of HSCT (P = 0.03) were associated with AUC levels. No statistically significant differences were found between transplant-related toxicity, acute and chronic graft versus host disease, engraftment, and AUC levels.
We concluded that older age at HSCT, intravenous administration of busulphan, cumulative, and prescribed dose of busulphan are associated with higher AUC levels. The absence of significant correlations between toxic events, graft failure, and AUC suggests the efficacy of busulphan concentrations monitoring in our patients.
本报告旨在描述儿童造血干细胞移植（HSCT）前使用白消安为基础的预处理方案的管理经验。
我们报告了接受口服和静脉注射白消安治疗的儿童中首剂AUC（浓度-时间曲线下面积，正常目标值在3600至4800 ng·h/mL之间）的值，并分析了该队列患者中一些临床变量的影响。
82例HSCT前接受白消安治疗的儿童符合研究条件：57例接受口服白消安，平均AUC为3586 ng·h/mL，而25例接受静脉注射白消安，平均AUC为4158 ng·h/mL。剂量调整基于首剂AUC。36例儿童（43.9%）剂量增加，26例患者（31.7%）剂量减少。HSCT时的年龄（P = 0.015）、白消安的累积剂量（mg/m）（P < 0.001）、规定的白消安剂量（mg/Kg）（P = 0.001）、静脉注射白消安（P < 0.001）、干细胞来源类型（P = 0.016）和HSCT类型（P = 0.03）与AUC水平相关。在移植相关毒性、急性和慢性移植物抗宿主病、植入和AUC水平之间未发现统计学显著差异。
我们得出结论，HSCT时年龄较大、静脉注射白消安、白消安的累积和规定剂量与较高的AUC水平相关。毒性事件、移植失败和AUC之间缺乏显著相关性表明在我们的患者中监测白消安浓度是有效的。
