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化疗后干细胞因子联合非格司亭可提高多发性骨髓瘤患者外周血祖细胞产量并减少单采需求:一项随机对照试验

Stem cell factor in combination with filgrastim after chemotherapy improves peripheral blood progenitor cell yield and reduces apheresis requirements in multiple myeloma patients: a randomized, controlled trial.

作者信息

Facon T, Harousseau J L, Maloisel F, Attal M, Odriozola J, Alegre A, Schroyens W, Hulin C, Schots R, Marin P, Guilhot F, Granena A, De Waele M, Pigneux A, Méresse V, Clark P, Reiffers J

机构信息

Department of Hematology, Service des Maladies du Sang,Hôpital Claude Huriez, 59037 Lille Cedex, France.

出版信息

Blood. 1999 Aug 15;94(4):1218-25.

Abstract

Stem cell factor (SCF) has been shown to synergize with filgrastim to mobilize CD34(+) cells into the peripheral blood. To determine if addition of SCF to chemotherapy and filgrastim reduces the number of leukaphereses required to achieve a target yield of 5 x 10(6) CD34(+) cells/kg, 102 patients with multiple myeloma were randomized to receive mobilization chemotherapy with cyclophosphamide (4 g/m(2)) and either SCF (20 micrograms/kg/d) combined with filgrastim (5 micrograms/kg/d) or filgrastim alone (5 micrograms/kg/d), administered daily until leukaphereses were completed. After collection, patients were treated with myeloablative therapy supported by autologous peripheral blood progenitor cell (PBPC) infusion and filgrastim (5 micrograms/kg/d). There was a significant difference between the treatment groups in the number of leukaphereses required to collect 5 x 10(6) CD34(+) cells/kg (median of 1 v 2 for SCF + filgrastim and filgrastim alone, respectively, P =.008). Patients receiving the combination of SCF plus filgrastim had a 3-fold greater chance of reaching 5 x 10(6) CD34(+) cells/kg in a single leukapheresis compared with patients mobilized with filgrastim alone. The median CD34(+) cell yield was significantly increased for the SCF group in the first leukapheresis (11.3 v 4.0 x 10(6)/kg, P =.003) and all leukaphereses (12.4 v 8.2 x 10(6)/kg, P =.007). Total colony-forming unit-granulocyte-macrophage (CFU-GM) and mononuclear cell counts were also significantly higher in the SCF group in the first leukapheresis and in all leukaphereses. As expected for patients mobilized to an optimal CD34(+) cell yield, the time to engraftment was similar between the 2 treatment groups. Cells mobilized with the combination of SCF plus filgrastim were thus considered effective and safe for achieving rapid engraftment. Treatment with SCF plus filgrastim was well tolerated, with mild to moderate injection site reactions being the most frequently reported adverse events. There were no serious allergic-like reactions to SCF. The addition of SCF to filgrastim after cyclophosphamide for PBPC mobilization resulted in a significant increase in CD34(+) cell yield and a concomitant reduction in the number of leukaphereses required to collect an optimal harvest of 5 x 10(6) CD34(+) cells/kg.

摘要

干细胞因子(SCF)已被证明可与非格司亭协同作用,将CD34(+)细胞动员至外周血中。为确定在化疗和非格司亭基础上加用SCF是否能减少达到5×10(6)个CD34(+)细胞/kg目标产量所需的白细胞分离术次数,102例多发性骨髓瘤患者被随机分组,接受环磷酰胺(4 g/m(2))动员化疗,其中一组接受SCF(20微克/千克/日)联合非格司亭(5微克/千克/日),另一组仅接受非格司亭(5微克/千克/日),每日给药直至白细胞分离术完成。采集后,患者接受自体外周血祖细胞(PBPC)输注和非格司亭(5微克/千克/日)支持的清髓性治疗。在采集5×10(6)个CD34(+)细胞/kg所需的白细胞分离术次数方面,治疗组间存在显著差异(SCF + 非格司亭组和仅非格司亭组的中位数分别为1次和2次,P = 0.008)。与仅用非格司亭动员的患者相比,接受SCF加非格司亭联合治疗的患者在单次白细胞分离术中达到5×10(6)个CD34(+)细胞/kg的几率高3倍。SCF组首次白细胞分离术(11.3对4.0×10(6)/kg,P = 0.003)和所有白细胞分离术(12.4对8.2×10(6)/kg,P = 0.007)的CD34(+)细胞产量中位数均显著增加。SCF组首次白细胞分离术和所有白细胞分离术的总集落形成单位 - 粒细胞 - 巨噬细胞(CFU - GM)和单核细胞计数也显著更高。正如预期的那样,对于动员至最佳CD34(+)细胞产量的患者,两个治疗组的植入时间相似。因此,SCF加非格司亭联合动员的细胞被认为对于实现快速植入是有效且安全的。SCF加非格司亭治疗耐受性良好,轻度至中度注射部位反应是最常报告的不良事件。未出现对SCF的严重过敏样反应。环磷酰胺后加用SCF进行PBPC动员可显著提高CD34(+)细胞产量,并同时减少采集5×10(6)个CD34(+)细胞/kg最佳收获量所需的白细胞分离术次数。

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