Pelus Louis M, Farag Sherif S
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana.
Stem Cells Cloning. 2011 Feb 27;4:11-22. doi: 10.2147/SCCAA.S6713. eCollection 2011.
Multiple myeloma and non-Hodgkin's lymphoma remain the most common indications for high-dose chemotherapy and autologous peripheral blood stem cell rescue. While a CD34+ cell dose of 1 × 10(6)/kg is considered the minimum required for engraftment, higher CD34+ doses correlate with improved outcome. Numerous studies, however, support targeting a minimum CD34+ cell dose of 2.0 × 10(6)/kg, and an "optimal" dose of 4 to 6 × 10(6)/kg for a single transplant. Unfortunately, up to 40% of patients fail to mobilize an optimal CD34+ cell dose using myeloid growth factors alone. Plerixafor is a novel reversible inhibitor of CXCR4 that significantly increases the mobilization and collection of higher numbers of hematopoietic progenitor cells. Two randomized multi-center clinical trials in patients with non-Hodgkin's lymphoma and multiple myeloma have demonstrated that the addition of plerixafor to granulocyte-colony stimulating factor increases the mobilization and yield of CD34+ cells in fewer apheresis days, which results in durable engraftment. This review summarizes the pharmacology and evidence for the clinical efficacy of plerixafor in mobilizing hematopoietic stem and progenitor cells, and discusses potential ways to utilize plerixafor in a cost-effective manner in patients with these diseases.
多发性骨髓瘤和非霍奇金淋巴瘤仍然是高剂量化疗及自体外周血干细胞救援最常见的适应证。虽然认为1×10⁶/kg的CD34⁺细胞剂量是植入所需的最低剂量，但较高的CD34⁺剂量与更好的预后相关。然而，众多研究支持单次移植的最低CD34⁺细胞剂量目标为2.0×10⁶/kg，“最佳”剂量为4至6×10⁶/kg。不幸的是，高达40%的患者仅使用髓系生长因子无法动员出最佳的CD34⁺细胞剂量。普乐沙福是一种新型的CXCR4可逆抑制剂，可显著增加更多造血祖细胞的动员和采集。两项针对非霍奇金淋巴瘤和多发性骨髓瘤患者的随机多中心临床试验表明，在粒细胞集落刺激因子基础上加用普乐沙福可在更少的单采天数内增加CD34⁺细胞的动员和产量，从而实现持久植入。本综述总结了普乐沙福在动员造血干细胞和祖细胞方面的药理学及临床疗效证据，并讨论了在这些疾病患者中以具有成本效益的方式使用普乐沙福的潜在方法。
