乳腺癌患者单纯使用粒细胞集落刺激因子（G-CSF）进行干细胞动员：与单次剂量（1×10微克/千克）相比，分剂量给药（2×5微克/千克）可获得更高的祖细胞产量。

Stem cell mobilization with G-CSF alone in breast cancer patients: higher progenitor cell yield by delivering divided doses (2 x 5 microg/kg) compared to a single dose (1 x 10 microg/kg).

作者信息

Kröger N, Zeller W, Hassan H T, Krüger W, Gutensohn K, Löliger C, Zander A R

机构信息

Bone Marrow Transplantation, University of Hamburg, Germany.

出版信息

Bone Marrow Transplant. 1999 Jan;23(2):125-9. doi: 10.1038/sj.bmt.1701549.

DOI:10.1038/sj.bmt.1701549

PMID:10197796

Abstract

We investigated the schedule dependency of G-CSF (10 microg/kg) alone in mobilizing peripheral blood progenitor cells (PBPC) in breast cancer patients. After a median of three cycles (range, 2-6) of anthracycline-based chemotherapy, 49 patients with breast cancer (stage II/III, > or = 10+ Ln n = 36; locally advanced/inflammatory n = 8, stage IV (NED) n = 5) underwent PBPC collection after steady-state mobilization either with 1 x 10 microg/kg (n = 27) or with 2 x 5 microg/kg (n = 22) G-CSF daily for 4 consecutive days until completion of apheresis. Apheresis was started on day 5. Priming with 2 x 5 microg/kg resulted in a higher median number of CD34+ cells (5.8 vs 1.9 x 10(6)/kg, P = 0.003), MNC (6.6 vs 2.6 x 10(8)/kg, P < 0.001) and CFU-GM (6.5 vs 1.3 x 10(4)/kg, P = 0.001) in the first apheresis than with 1 x 10 microg/kg. Also the overall number of collected BFU-E was higher in the 2 x 5 microg group (9.2 vs 3.1 x 10(4)/kg; P = 0.01). After high-dose chemotherapy with cyclophosphamide/thiotepa/mitoxantrone (n = 46) hematopoietic engraftment with leukocyte count > 1.0/nl was reached in both groups after a median of 10 days (range, 8-15) and with platelets count > 50/nl after 12 (range, 9-40) and 13 days (range, 12-41), respectively. A threshold of > 2.5 x 10(6)/kg reinfused CD34+ cells ensured rapid platelet engraftment (12 vs 17 days; P = 0.12). Therefore, the target of collecting > 2.5 x 10(6) CD34+ cells was achieved in 21/27 (80%) patients of the 1 x 10 microg group and in 21/22 (95%) patients of the 2 x 5 microg/kg group with a median of two aphereses (range, 1-4). None in the 10 microg/kg group, but 6/22 (28%) patients in the 2 x 5 microg/kg group required only one apheresis procedure, resulting in fewer apheresis procedures in the 2 x 5 microg/kg group (mean, 1.8 vs 2.3, P = 0.01). These results demonstrate that priming with 10 microg/kg G-CSF alone is well tolerated and effective in mobilizing sufficient numbers of CD34+ cells in breast cancer patients and provide prompt engraftment after CTM high-dose chemotherapy. G-CSF given 5 microg/kg twice daily (2 x 5 microg) leads to a higher harvest of CD34+ cells and required fewer apheresis procedures than when given 10 microg/kg once daily (1 x 10 microg).

摘要

我们研究了单独使用粒细胞集落刺激因子（G-CSF，10微克/千克）动员乳腺癌患者外周血祖细胞（PBPC）的给药方案依赖性。在接受以蒽环类药物为基础的化疗，中位疗程为三个周期（范围2 - 6个周期）后，49例乳腺癌患者（II/III期，≥10 + Ln n = 36；局部晚期/炎性n = 8，IV期（无疾病证据）n = 5）在稳态动员后进行PBPC采集，其中27例患者每天给予1×10微克/千克G-CSF，22例患者每天给予2×5微克/千克G-CSF，连续4天，直至完成单采术。单采术于第5天开始。2×5微克/千克剂量启动动员后，首次单采术中CD34 +细胞的中位数（5.8对1.9×10⁶/千克，P = 0.003）、单核细胞（MNC，6.6对2.6×10⁸/千克，P < 0.001）和粒-巨噬细胞集落形成单位（CFU-GM，6.5对1.3×10⁴/千克，P = 0.001）均高于1×10微克/千克剂量组。2×5微克组采集的爆式红系集落形成单位（BFU-E）总数也更高（9.2对3.1×10⁴/千克；P = 0.01）。在接受环磷酰胺/噻替派/米托蒽醌大剂量化疗（n = 46）后，两组患者的造血均得以重建，白细胞计数>1.0/微升的中位时间为10天（范围8 - 15天），血小板计数>50/微升的中位时间分别为12天（范围9 - 40天）和13天（范围12 - 41天）。回输的CD34 +细胞>2.5×10⁶/千克的阈值可确保血小板快速植入（12天对17天；P = 0.12）。因此，1×10微克组27例患者中有21例（80%）、2×5微克/千克组22例患者中有21例（95%）达到了采集>2.5×10⁶个CD34 +细胞的目标，中位单采次数为两次（范围1 - 4次）。10微克/千克组无患者，但2×5微克/千克组有6/22（28%）的患者仅需一次单采程序，使得2×5微克/千克组的单采程序更少（平均1.8次对2.3次，P = 0.01）。这些结果表明，单独使用10微克/千克G-CSF启动动员耐受性良好，能有效动员足够数量的CD34 +细胞，且在环磷酰胺/噻替派/米托蒽醌大剂量化疗后能促进造血植入。每天两次给予5微克/千克G-CSF（2×5微克）比每天一次给予10微克/千克G-CSF（1×10微克）能收获更多的CD34 +细胞，且所需的单采程序更少。