Institute of Medical and Veterinary Science, Adelaide, Australia.
Blood. 2011 Oct 27;118(17):4530-40. doi: 10.1182/blood-2011-06-318220. Epub 2011 Aug 10.
Transplantation with 2-5 × 10(6) mobilized CD34(+)cells/kg body weight lowers transplantation costs and mortality. Mobilization is most commonly performed with recombinant human G-CSF with or without chemotherapy, but a proportion of patients/donors fail to mobilize sufficient cells. BM disease, prior treatment, and age are factors influencing mobilization, but genetics also contributes. Mobilization may fail because of the changes affecting the HSC/progenitor cell/BM niche integrity and chemotaxis. Poor mobilization affects patient outcome and increases resource use. Until recently increasing G-CSF dose and adding SCF have been used in poor mobilizers with limited success. However, plerixafor through its rapid direct blockage of the CXCR4/CXCL12 chemotaxis pathway and synergy with G-CSF and chemotherapy has become a new and important agent for mobilization. Its efficacy in upfront and failed mobilizers is well established. To maximize HSC harvest in poor mobilizers the clinician needs to optimize current mobilization protocols and to integrate novel agents such as plerixafor. These include when to mobilize in relation to chemotherapy, how to schedule and perform apheresis, how to identify poor mobilizers, and what are the criteria for preemptive and immediate salvage use of plerixafor.
以 2-5×10(6)个/kg 体重的动员 CD34(+)细胞进行移植可降低移植成本和死亡率。动员最常使用重组人 G-CSF 联合或不联合化疗,但一部分患者/供者无法动员足够的细胞。骨髓疾病、既往治疗和年龄是影响动员的因素,但遗传因素也有影响。动员失败可能是因为影响造血干细胞/祖细胞/骨髓龛完整性和趋化性的变化。动员不良会影响患者的预后并增加资源的使用。直到最近,增加 G-CSF 剂量并添加 SCF 已用于动员不良的患者,但效果有限。然而,plerixafor 通过其快速直接阻断 CXCR4/CXCL12 趋化作用途径,并与 G-CSF 和化疗协同作用,已成为动员的新的重要药物。其在初始和动员失败的患者中的疗效已得到充分证实。为了在动员不良的患者中最大限度地收获造血干细胞,临床医生需要优化当前的动员方案,并整合新型药物,如 plerixafor。这些包括与化疗相关的动员时机、如何安排和进行单采、如何识别动员不良的患者,以及预防性和即时补救使用 plerixafor 的标准。