Phase I study of the safety and pharmacokinetics of plerixafor in children undergoing a second allogeneic hematopoietic stem cell transplantation for relapsed or refractory leukemia.
Phase I study of the safety and pharmacokinetics of plerixafor in children undergoing a second allogeneic hematopoietic stem cell transplantation for relapsed or refractory leukemia.
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DOI：
10.1016/j.bbmt.2014.04.020
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发表时间：
2014-08
期刊：
影响因子：
--
通讯作者：
Leung W
中科院分区：
文献类型：
--
作者：
Srinivasan A;Panetta JC;Cross SJ;Pillai A;Triplett BM;Shook DR;Dallas MH;Hartford C;Sunkara A;Kang G;Jacobsen J;Choi J;Leung W
作为异基因造血干细胞移植（HSCT）化疗致敏的调节方案的一部分，普利沙福在儿童中的安全性、药代动力学和生物学效应尚未得到研究。这是一项I期研究，旨在评估其在第4天（1级）、第4天和第3天（2级），或第4天、第3天和第2天（3级）静脉给药剂量0.24 mg/kg，与氟达拉滨、硫替帕、美伐兰和兔抗胸腺细胞球蛋白联合治疗难治性或复发性白血病儿童的第二次异体造血干细胞移植的耐受性。在给药前后对血液和骨髓进行免疫表型分析。12名患者入组。所有3个水平的普立沙福耐受性良好，无剂量限制性毒性。美国国家癌症研究所1级或2级的短暂性胃肠道副作用是最常见的不良事件。浓度-时间曲线下的面积随剂量水平成比例增加。普立沙替清除率在男性中较高，且与体重和肾小球滤过率呈线性增加。从剂量水平1到剂量水平3，清除率降低，消除半衰期显著增加（P < 0.001）。在生物学上，给药后骨髓和外周血中cxcr4阳性的母细胞和淋巴细胞比例增加。
The safety, pharmacokinetics and biological effect of plerixafor in children as part of a conditioning regimen for chemo-sensitization in allogeneic hematopoietic stem cell transplantation (HSCT) have not been studied. This is a phase I study of plerixafor designed to evaluate its tolerability at dose of 0.24 mg/kg given intravenously on day -4 (level 1), day -4, and day -3 (level 2), or day -4, -3, and day -2 (level 3) in combination with fludarabine, thiotepa, melphalan, and rabbit anti-thymocytic globulin for a second allogeneic HSCT in children with refractory or relapsed leukemia. Immunophenotype analysis was performed on blood and bone marrow prior to and after plerixafor administration. Twelve patients were enrolled. Plerixafor at all 3 levels was well tolerated without dose-limiting toxicity. Transient gastrointestinal side effects of National Cancer Institute grade 1 or 2 in severity were the most common adverse events. The area under the concentration-time curve increased proportionally to the dose level. Plerixafor clearance was higher in males, and increased linearly with body weight, and glomerular filtration rate. The clearance decreased and the elimination half-life increased significantly from dose level 1 to 3 (P < 0.001). Biologically, the proportion of CXCR4-positive blasts and lymphocytes both in the bone marrow and peripheral blood, increased after plerixafor administration.