Rapid mobilization of CD34+cells following administration of the CXCR4 antagonist AMD3100 to patients with multiple myeloma and non-Hodgkin's lymphoma
Rapid mobilization of CD34+cells following administration of the CXCR4 antagonist AMD3100 to patients with multiple myeloma and non-Hodgkin's lymphoma
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DOI：
10.1200/jco.2004.07.131
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发表时间：
2004-03-15
影响因子：
45.3
通讯作者：
DiPersio, JF
中科院分区：
文献类型：
--
作者：
Devine, SM;Flomenberg, N;DiPersio, JF
趋化因子受体CXCR4及其配体基质衍生因子-1之间的相互作用调节造血干细胞运输，AMD3100是一种CXCR4拮抗剂，可诱导健康志愿者体内CD34+细胞的快速动员。我们进行了一项评估AMD3100在多发性骨髓瘤（MM）和非霍奇金淋巴瘤（NHL）患者中的安全性和临床效果的i期研究。患者和方法13例患者（MM, n = 7； NHL, n = 6）接受AMD3100治疗，剂量为160杯/kg （n = 6）或240杯/kg （n = 7）。注射后4、6小时检测WBC和外周血CD34+细胞计数。结果AMD3100在单次注射后4和6小时引起WBC和PB CD34+计数的快速和有统计学意义的增加。注射后4小时（P = 0.002）和6小时（P = 0.003）， CD34+细胞的绝对计数分别从基线的2.6 +/- 0.7/muL（平均+/- SE）增加到15.6 +/- 3.9/muL和16.2 +/- 4.3/muL。在AMD3100后4和6小时观察到的CD34+细胞绝对计数，240杯/kg组（分别为19.3 +/- 6.9/muL和20.4 +/- 7.6/muL）高于160杯/kg组（分别为11.3 +/- 2.7/muL和11.3 +/- 2.5/muL）。该药耐受性良好，仅发生1级毒性。结论AMD3100是一种安全有效的药物，可快速动员既往化疗患者的CD34+细胞。进一步研究联合粒细胞集落刺激因子在淋巴细胞恶性肿瘤患者中的应用是必要的。
Purpose Interactions between the chemokine receptor CXCR4 and its ligand stromal derived factor-1 regulate hematopoietic stem-cell trafficking, AMD3100 is a CXCR4 antagonist that induces rapid mobilization of CD34+ cells in healthy volunteers. We performed a phase 1 study assessing the safety and clinical effects of AMD3100 in patients with multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL).Patients and Methods Thirteen patients (MM, n = 7; NHL, n = 6) received AMD3100 at a dose of either 160 mug/kg (n = 6) or 240 mug/kg (n = 7). WBC and peripheral blood (PB) CD34+ cell counts were analyzed at 4 and 6 hours following injection.Results AMD3100 caused a rapid and statistically significant increase in the total WBC and PB CD34+ counts at both 4 and 6 hours following a single injection. The absolute CD34+ cell count increased from a baseline of 2.6 +/- 0.7/muL (mean +/- SE) to 15.6 +/- 3.9/muL and 16.2 +/- 4.3/muL at 4 hours (P = .002) and 6 hours after injection (P = .003), respectively. The absolute CD34+ cell counts observed at 4 and 6 hours following AMD3100 were higher in the 240 mug/kg group (19.3 +/- 6.9/muL and 20.4 +/- 7.6/muL, respectively) compared with the 160 mug/kg group (11.3 +/- 2.7/muL and 11.3 +/- 2.5/muL, respectively). The drug was well tolerated and only grade 1 toxicities were encountered.Conclusion AMD3100 appears to be a safe and effective agent for the rapid mobilization of CD34+ cells in patients who have received prior chemotherapy. Further studies in combination with granulocyte colony-stimulating factor in patients with lymphoid malignancies are warranted.