Phase I/II Study of Intravenous Plerixafor Added to a Mobilization Regimen of Granulocyte Colony-Stimulating Factor in Lymphoma Patients Undergoing Autologous Stem Cell Collection.
Phase I/II Study of Intravenous Plerixafor Added to a Mobilization Regimen of Granulocyte Colony-Stimulating Factor in Lymphoma Patients Undergoing Autologous Stem Cell Collection.
复制标题
在接受自体干细胞采集的淋巴瘤患者的粒细胞集落刺激因子动员方案中添加静脉注射 Plerixafor 的 I/II 期研究。
DOI：
10.1016/j.bbmt.2017.04.024
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
DiPersio,John
中科院分区：
文献类型：
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作者：
Cashen,AmandaF;Rettig,Michael;Gao,Feng;Smith,Angela;Abboud,Camille;Stockerl-Goldstein,Keith;Vij,Ravi;Uy,Geoffrey;Westervelt,Peter;DiPersio,John
普乐沙福与粒细胞集落刺激因子（G-CSF）皮下给药可改善淋巴瘤和多发性骨髓瘤患者的自体干细胞收集。静脉注射（i. v.）普乐沙福的给药允许普乐沙福在血液分离术的同一天给药，并且它可以改善干细胞收集。本项I/II期研究的主要目的是确定普乐沙福静脉注射的最大耐受剂量以及普乐沙福静脉注射+ G-CSF从淋巴瘤患者中动员≥ 2 × 106 CD 34+细胞/kg的疗效。在I期，25例患者接受G-CSF +普乐沙福静脉注射递增剂量治疗;在II期，36例患者接受G-CSF +普乐沙福40 mg/kg治疗。治疗耐受性良好。61例患者中有59例（98%）符合采集目标，61例患者中有47例（77%）在中位2个单采日内采集了≥ 5.0 × 106 CD 34+细胞/kg。CD 34+造血干细胞和祖细胞（HSPC）分析显示，G-CSF动员的移植物富含CD 34 + CD 45 RA-CD 123 +/-原始HSPC，而普乐沙福优先动员CD 34 + CD 45 RA + CD 123 ++浆细胞样树突状细胞前体。总之，普乐沙福静脉注射与G-CSF联合用于动员淋巴瘤患者的干细胞时耐受性良好且有效，动员动力学和干细胞收集优于皮下给药。
Plerixafor, given subcutaneously with granulocyte colony–stimulating factor (G-CSF), improves autologous stem cell collection in patients with lymphoma and multiple myeloma. Intravenous (i.v.) administration of plerixafor allows administration of plerixafor on the same day as pheresis and it may improve stem cell collection. The primary objectives of this phase I/II study were to determine the maximum tolerated dose of i.v. plerixafor and the efficacy of i.v. plerixafor + G-CSF to mobilize ≥ 2 × 106CD34+cells/kg from patients with lymphoma. In phase I, 25 patients were treated with G-CSF + i.v. plerixafor at escalating doses; in phase II, 36 patients were treated with G-CSF + plerixafor .40 mg/kg. The treatment was well tolerated. Fifty-nine of 61 patients (98%) met the collection goal and 47 of 61 patients (77%) collected ≥ 5.0 × 106CD34+cells/kg in a median of 2 pheresis days. Analysis of CD34+hematopoietic stem and progenitor cells (HSPCs) revealed that G-CSF–mobilized grafts were enriched with CD34+CD45RA-CD123+/-primitive HSPCs whereas plerixafor preferentially mobilized CD34+CD45RA+CD123++plasmacytoid dendritic cell precursors. In conclusion, i.v. plerixafor is well tolerated and effective when added to G-CSF for the mobilization of stem cells from patients with lymphoma, with mobilization kinetics and stem cell collections that compare favorably with subcutaneous dosing.