自体血祖细胞的免疫动员：对采集的细胞亚群的直接影响。
Immune mobilization of autologous blood progenitor cells: direct influence on the cellular subsets collected.
机构信息
Blood and Marrow Transplant Program, Section of Hematology and Oncology, 1 Medical Center Drive, Dartmouth Hitchcock Medical Center, Norris Cotton Cancer Center, Lebanon, NH 03756, USA.
出版信息
Cytotherapy. 2010 Dec;12(8):1013-21. doi: 10.3109/14653249.2010.515580. Epub 2010 Sep 27.
BACKGROUND AIMS
A phase I trial examined the ability of immunotherapy to mobilize progenitor and activated T cells.
METHODS
Interleukin (IL)-2 was administered subcutaneously for 11 days, with granulocyte (G)-colony-stimulating factor (CSF) (5 mcg/kg/day) and granulocyte-macrophage (GM)-CSF (7.5 mcg/kg/day) added for the last 5 days. Leukapheresis was initiated on day 11. Thirteen patients were treated (myeloma n = 11, non-Hodgkin's lymphoma n = 2).
RESULTS
Toxicities were minimal. IL-2 was stopped in two patients because of capillary leak (n = 1) and diarrhea (n = 1). Each patient required 2.5 leukaphereses (median; range 1-3) to collect 3.2 x 10⁶ CD34+ cells/kg (median; range 1.9-6.6 x 10⁶/kg). Immune mobilization increased the number of CD3+ CD8+ T cells (P = 0.002), CD56+ natural killer (NK) cells (P = 0.0001), CD8+ CD56+ T cells (P = 0.002) and CD4+ CD25+ cells (P = 0.0001) compared with cancer patients mobilized with G-CSF alone. There was increased lysis of myeloma cells after 7 days (P = 0.03) or 11 days (P = 0.02). The maximum tolerated dose of IL-2 was 1 x 10⁶ IU/m²/day.
CONCLUSIONS
Immune mobilization is well tolerated with normal subsequent marrow engraftment. As cells within the graft influence lymphocyte recovery, an increased number of functional lymphocytes may result in more rapid immune reconstitution.
背景目的
一项 I 期试验研究了免疫疗法动员祖细胞和激活 T 细胞的能力。
方法
皮下给予白细胞介素（IL）-211 天，最后 5 天加用粒细胞（G）-集落刺激因子（CSF）（5 mcg/kg/天）和粒细胞-巨噬细胞（GM）-CSF（7.5 mcg/kg/天）。第 11 天开始白细胞分离。13 例患者接受治疗（骨髓瘤 n=11，非霍奇金淋巴瘤 n=2）。
结果
毒性最小。因毛细血管渗漏（n=1）和腹泻（n=1），有 2 例患者停止使用 IL-2。每位患者需要 2.5 次白细胞分离术（中位数；范围 1-3），以收集 3.2 x 10⁶CD34+细胞/kg（中位数；范围 1.9-6.6 x 10⁶/kg）。免疫动员增加了 CD3+CD8+T 细胞（P=0.002）、CD56+自然杀伤（NK）细胞（P=0.0001）、CD8+CD56+T 细胞（P=0.002）和 CD4+CD25+细胞（P=0.0001）的数量，与单独使用 G-CSF 动员的癌症患者相比。骨髓瘤细胞的溶解在 7 天（P=0.03）或 11 天（P=0.02）后增加。IL-2 的最大耐受剂量为 1 x 10⁶IU/m²/天。
结论
免疫动员耐受性良好，随后骨髓植入正常。由于移植物内的细胞影响淋巴细胞恢复，更多数量的功能性淋巴细胞可能导致更快的免疫重建。
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