Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Division of Neoplastic Diseases and Related Disorders, Medical College of Wisconsin, Milwaukee, WI, USA.
Int J Hematol. 2009 Dec;90(5):627-634. doi: 10.1007/s12185-009-0439-6. Epub 2009 Dec 9.
Immunomodulation with cytokines was used to improve the result of high-dose chemotherapy (HDC)/autologous hematopoietic stem cell transplantation (AHST). We examined the use of IL-2 and growth factors for mobilization, ex vivo activation of peripheral blood stem cell (PBSC) and maintenance therapy after HDC/AHST in metastatic breast cancer. Eligible patients with metastatic breast cancer for HDC/AHST were assigned to 1 of 3 protocols for PBSC mobilization: G-CSF (group 1); IL-2 + G-CSF (group 2); or IL-2 + G-CSF + GM-CSF (group 3). HDC with cyclophosphamide, carmustine and thiotepa was given from day -7 to -5. PBSCs were treated ex vivo with IL-2 for 24 h and reinfused on day 0. Maintenance therapy included low-dose IL-2, followed by 2 courses of intermediate-dose IL-2. GM-CSF was given from day 1 until neutrophil recovery. Thirty-four patients (10 in group 1, 14 in group 2, and 10 in group 3) were included. Comparable numbers of CD34(+) cells were collected from all 3 groups; incremental increases of CD3(+) cells were collected from groups 1 to 2 and to 3 (p = 0.03). Major adverse effects from IL-2 were fever, hypotension and fatigue; no treatment-related mortality was seen. At a median follow-up of 790.5 days (range 150-2,722 days), median progression-free survival was 434 days and median overall survival was 1,432 days. Estimated 3-year progression-free and overall survival rates were 31 and 57%. Our study suggested that the use of IL-2 and growth factors immunomodulation with HDC/AHST was feasible with comparable survival rates.
细胞因子的免疫调节被用于改善高剂量化疗（HDC）/自体造血干细胞移植（AHST）的结果。我们研究了白细胞介素 2（IL-2）和生长因子在转移性乳腺癌患者 HDC/AHST 中的动员、外周血干细胞（PBSC）的体外激活和维持治疗中的应用。符合 HDC/AHST 条件的转移性乳腺癌患者被分配到以下 3 种 PBSC 动员方案中的 1 种：G-CSF（第 1 组）；IL-2+G-CSF（第 2 组）；或 IL-2+G-CSF+GM-CSF（第 3 组）。从-7 天到-5 天给予环磷酰胺、卡莫司汀和噻替哌的 HDC。将 PBSC 用 IL-2 体外处理 24 小时，并在第 0 天回输。维持治疗包括低剂量 IL-2，随后进行 2 个中间剂量 IL-2 疗程。从第 1 天开始给予 GM-CSF，直至中性粒细胞恢复。34 例患者（第 1 组 10 例，第 2 组 14 例，第 3 组 10 例）入组。从所有 3 组中采集了相当数量的 CD34+细胞；从第 1 组到第 2 组再到第 3 组，CD3+细胞的增量增加（p=0.03）。IL-2 的主要不良反应是发热、低血压和疲劳；未观察到与治疗相关的死亡。在中位随访 790.5 天（范围 150-2722 天）后，中位无进展生存期为 434 天，总生存期为 1432 天。估计 3 年无进展生存率和总生存率分别为 31%和 57%。我们的研究表明，使用 IL-2 和生长因子免疫调节联合 HDC/AHST 是可行的，且生存率相当。
