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大剂量依托泊苷联合粒细胞集落刺激因子用于动员外周血祖细胞:三种剂量水平下的疗效和毒性

High-dose etoposide with granulocyte colony-stimulating factor for mobilization of peripheral blood progenitor cells: efficacy and toxicity at three dose levels.

作者信息

Kanfer E J, McGuigan D, Samson D, Abboudi Z, Abrahamson G, Apperley J F, Chilcott S, Craddock C, Davis J, MacDonald C, Macdonald D, Olavarria E, Philpott N, Rustin G J, Seckl M J, Sekhar M, Stern S, Newlands E S

机构信息

Department of Haematology, Imperial College School of Medicine at Charing Cross Hospital, Hammersmith Hospitals NHS Trust, London, UK.

出版信息

Br J Cancer. 1998 Oct;78(7):928-32. doi: 10.1038/bjc.1998.603.

Abstract

High-dose etoposide (2.0-2.4 g m(-2)) with granulocyte colony-stimulating factor (G-CSF) is an effective strategy to mobilize peripheral blood progenitor cells (PBPCs), although in some patients this is associated with significant toxicity. Sixty-three patients with malignancy were enrolled into this non-randomized sequential study. The majority (55/63, 87%) had received at least two prior regimens of chemotherapy, and seven patients had previously failed to mobilize following high-dose cyclophosphamide with G-CSF. Consecutive patient groups received etoposide at three dose levels [2.0 g m(-2) (n = 22), 1.8 g m(-2) (n = 20) and 1.6 g m(-2) (n = 21)] followed by daily G-CSF. Subsequent leukaphereses were assayed for CD34+ cell content, with a target total collection of 2.0 x 10(6) CD34+ cells kg(-1). Toxicity was assessed by the development of significant mucositis, the requirement for parenteral antibiotics or blood component support and rehospitalization incidence. Ten patients (16%) had less than the minimum target yield collected. Median collections in the three groups were 4.7 (2 g m(-2)), 5.7 (1.8 g m(-2)) and 6.5 (1.6 g m(-2)) x 10(6) CD34+ cells kg(-1). Five of the seven patients who had previously failed cyclophosphamide mobilization achieved more than the target yield. Rehospitalization incidence was significantly lower in patients receiving 1.6 g m(-2) etoposide than in those receiving 2.0 g m(-2) (P = 0.03). These data suggest that high-dose etoposide with G-CSF is an efficient mobilization regimen in the majority of heavily pretreated patients, including those who have previously failed on high-dose cyclophosphamide with G-CSF. An etoposide dose of 1.6 g m(-2) appears to be as effective as higher doses but less toxic.

摘要

大剂量依托泊苷(2.0 - 2.4 g m(-2))联合粒细胞集落刺激因子(G-CSF)是动员外周血祖细胞(PBPCs)的有效策略,尽管在一些患者中这与显著的毒性相关。63例恶性肿瘤患者被纳入这项非随机序贯研究。大多数患者(55/63,87%)此前至少接受过两种化疗方案,7例患者此前在接受大剂量环磷酰胺联合G-CSF治疗后未能成功动员。连续的患者组接受三种剂量水平的依托泊苷[2.0 g m(-2)(n = 22)、1.8 g m(-2)(n = 20)和1.6 g m(-2)(n = 21)],随后每日给予G-CSF。对随后的白细胞分离物检测CD34+细胞含量,目标是总共采集2.0×10(6)个CD34+细胞/kg(-1)。通过严重黏膜炎的发生、肠外抗生素或血液成分支持的需求以及再住院发生率来评估毒性。10例患者(16%)采集的细胞数量低于最低目标产量。三组的中位采集量分别为4.7(2 g m(-2))、5.7(1.8 g m(-2))和6.5(1.6 g m(-2))×10(6)个CD34+细胞/kg(-1)。7例此前环磷酰胺动员失败的患者中有5例采集量超过目标产量。接受1.6 g m(-2)依托泊苷的患者再住院发生率显著低于接受2.0 g m(-2)依托泊苷的患者(P = 0.03)。这些数据表明,大剂量依托泊苷联合G-CSF对大多数经过大量预处理的患者,包括那些此前接受大剂量环磷酰胺联合G-CSF治疗失败的患者,是一种有效的动员方案。1.6 g m(-2)的依托泊苷剂量似乎与更高剂量一样有效,但毒性较小。

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