Tuchman Sascha A, Bacon Wendi A, Huang Li-Wen, Long Gwynn, Rizzieri David, Horwitz Mitchell, Chute John P, Sullivan Keith, Morris Engemann Ashley, Yopp Amanda, Li Zhiguo, Corbet Kelly, Chao Nelson, Gasparetto Cristina
Division of Hematologic Malignancies and Cellular Therapy, Duke Cancer Institute, Durham, North Carolina.
Department of Medicine, Duke University Medical Center, Durham, North Carolina.
J Clin Apher. 2015 Jun;30(3):176-82. doi: 10.1002/jca.21360. Epub 2014 Oct 8.
High-dose cyclophosphamide (Cy) is frequently employed for peripheral blood mobilization of hematopoietic stem cells before high-dose chemotherapy with autologous stem cell transplantation (ASCT) in multiple myeloma (MM). The benefit of mobilization with Cy over filgrastim (granulocyte colony-stimulating factor; G-CSF) alone is unclear. Between 2000 and 2008, 167 patients with newly diagnosed MM underwent single ASCT after melphalan conditioning at our institution. Seventy-three patients were mobilized with G-CSF alone, and 94 patients with Cy plus G-CSF (Cy+G-CSF). We retrospectively analyzed Cy's impact on both toxicity and efficacy. Mobilization efficiency was augmented by Cy; a mean total of 12 versus 5.8 × 10(6) CD34+ cells/kg were collected from patients mobilized with Cy+G-CSF versus G-CSF, respectively, (P < 0.01), over a mean of 1.6 versus 2.2 days of peripheral blood apheresis (p = 0.001). Mobilization-related toxicity was also, however, augmented by Cy; 14% of Cy+G-CSF patients were hospitalized because of complications versus none receiving G-CSF (P < 0.0001). Toxicity, including death, related to ASCT was similar between cohorts. Regarding long-term outcomes, multivariate analysis revealed no difference for Cy+G-CSF versus G-CSF (hazard ratio 0.8 for event-free survival [95% confidence interval {CI} 0.57-1.25] and 0.96 for overall survival [95% CI 0.61-1.54]). In summary, we show that mobilization with Cy increases toxicity without positively impacting long-term outcomes in MM. Our findings place into question Cy's benefit as a routine component of stem cell mobilization regimens in MM. Randomized trials are needed to elucidate the risks and benefits of Cy more definitively.
大剂量环磷酰胺(Cy)常用于多发性骨髓瘤(MM)患者在接受高剂量化疗及自体干细胞移植(ASCT)前进行外周血造血干细胞动员。与单独使用非格司亭(粒细胞集落刺激因子;G-CSF)相比,使用Cy进行动员的益处尚不清楚。2000年至2008年期间,167例新诊断的MM患者在我院接受美法仑预处理后进行了单次ASCT。73例患者仅使用G-CSF进行动员,94例患者使用Cy加G-CSF(Cy+G-CSF)进行动员。我们回顾性分析了Cy对毒性和疗效的影响。Cy提高了动员效率;从接受Cy+G-CSF动员的患者与接受G-CSF动员的患者中分别平均采集到12×10⁶与5.8×10⁶个CD34⁺细胞/kg(P<0.01),外周血单采的平均天数分别为1.6天与2.2天(p = 0.001)。然而,Cy也增加了与动员相关的毒性;14%接受Cy+G-CSF的患者因并发症住院,而接受G-CSF的患者无一人住院(P<0.0001)。两组间与ASCT相关的毒性(包括死亡)相似。关于长期结局,多变量分析显示Cy+G-CSF与G-CSF之间无差异(无进展生存的风险比为0.8 [95%置信区间{CI} 0.57 - 1.25],总生存的风险比为0.96 [95% CI 0.61 - 1.54])。总之,我们表明在MM中使用Cy进行动员增加了毒性,而对长期结局没有积极影响。我们的研究结果使Cy作为MM干细胞动员方案常规组成部分的益处受到质疑。需要进行随机试验以更明确地阐明Cy的风险和益处。