Chabannon Christian, Bijou Fontanet, Miclea Jean-Michel, Milpied Noel, Grouin Jean-Marie, Mohty Mohamad
Institut Paoli-Calmettes, Centre de Lutte Contre le Cancer.
Université d'Aix-Marseille.
Transfusion. 2015 Sep;55(9):2149-57. doi: 10.1111/trf.13141. Epub 2015 May 13.
High-dose chemotherapy supported with autologous stem cell transplantation is a standard therapeutic option for a subset of patients with lymphoid malignancies. Cell procurement is nowadays done almost exclusively through cytapheresis, after mobilization of hematopoietic stem and progenitor cells (HSPCs) from the marrow to peripheral blood (PB). The egress of HSPCs out of hematopoietic niches occurs in various physiologic or nonhomeostatic situations; pharmacologic approaches include the administration of acutely myelosuppressive agents or hematopoietic growth factors such as recombinant human granulocyte-colony-stimulating factor (rHuG-CSF). The introduction of plerixafor, a first-of-its-class molecule that reversibly inhibits the interaction between the chemokine CXCL-12 (also known as SDF-1) and its receptor CXCR-4, has offered new opportunities for the so-called "poor mobilizers" who achieve insufficient mobilization and/or collection with conventional approaches.
Because of the lack of consensus on a definition for poor mobilizers and the relatively high cost of plerixafor, French competent authorities have mandated a postmarketing survey on its use in routine practice.
We report here the results of this nationwide survey that confirms the clinical efficacy of plerixafor, even in the subset of patients who barely increased PB CD34+ cell count in response to rHuG-CSF-containing mobilization regimen. Furthermore, analysis of this registry showed that despite heterogeneity in medical practices, the early-"on-demand" or "preemptive"-introduction of plerixafor was widely used and did not result in an excess of prescriptions, beyond its expected use at the time when marketing authorization was granted.
自体干细胞移植支持下的大剂量化疗是一部分淋巴系统恶性肿瘤患者的标准治疗选择。如今,在造血干细胞和祖细胞(HSPCs)从骨髓动员至外周血(PB)后,细胞采集几乎完全通过血细胞分离术进行。HSPCs从造血龛中逸出发生在各种生理或非稳态情况下;药理学方法包括给予急性骨髓抑制药物或造血生长因子,如重组人粒细胞集落刺激因子(rHuG-CSF)。普乐沙福的引入,这是一种一流的分子,可逆性抑制趋化因子CXCL-12(也称为SDF-1)与其受体CXCR-4之间的相互作用,为那些采用传统方法动员和/或采集不足的所谓“动员不佳者”提供了新的机会。
由于对动员不佳者的定义缺乏共识,且普乐沙福成本相对较高,法国主管当局要求对其在常规实践中的使用进行上市后调查。
我们在此报告这项全国性调查的结果,该结果证实了普乐沙福的临床疗效,即使在对含rHuG-CSF的动员方案反应中PB CD34+细胞计数几乎没有增加的患者亚组中也是如此。此外,对该登记处的分析表明,尽管医疗实践存在异质性,但普乐沙福的早期“按需”或“先发制人”引入被广泛使用,且并未导致超出其上市授权时预期使用量的过量处方。