Bojko P, Pawloski D, Stellberg W, Schröder J K, Seeber S
University of Essen Medical School, Department of Internal Medicine (Cancer Research), West German Cancer Center, Hufelandstrasse 55, 45122 Essen, Germany.
Ann Hematol. 2002 Sep;81(9):522-8. doi: 10.1007/s00277-002-0535-7. Epub 2002 Sep 24.
The purpose of this investigation was to study thrombopoietin (TPO) and Flt3 ligand (FL) serum levels in the course of peripheral blood stem cell (PBSC) mobilization and high-dose chemotherapy (HDC) and to correlate the values with stem cell yield and engraftment. Thirty-nine patients were included. PBSC were mobilized by chemotherapy followed by two body surface area-dependent doses of glycosylated recombinant human granulocyte colony-stimulating factor (rhu-G-CSF, lenograstim). PBSC could be harvested in 35 patients and 30 received a total of 62 courses of HDC (1-3 per patient). Fifty-six were analyzed and TPO and FL serum levels were measured at the start of PBSC mobilization, at the first PBSC collection, on the day of PBSC infusion, and until engraftment. Mean baseline TPO and FL serum levels were 173 pg/ml and 192 pg/ml and increased to 493 and 323 pg/ml at the start of PBSC collection. Maximum values were 2279 pg/ml TPO after HDC 1 and 2375 pg/ml after HDC 2, while the mean maximum serum levels for FL were 1181 and 1236 pg/ml after HDC 1 and 2 and PBSC transfusion, respectively. FL serum levels at the start of PBSC mobilization correlated with the total yield of CD34+ cells (17.61+/-18.8x10(6)/kg body weight, r=0.81), while TPO serum levels on days 11-13 after PBSC infusion were inversely correlated with the amount of transfused CD34+61+62+ cells (r=-0.88 and -0.79 for HDC 1 and 2). There was no strong correlation between TPO or FL serum levels and WBC and platelet engraftment. In conclusion, chemotherapy followed by glycosylated rhu-G-CSF induced elevated serum levels of TPO and to a lower degree of FL at the start of PBSC collection. The maximum increase was 13.7-fold for TPO and 6.4-fold for FL after PBSC infusion indicating endogenous release which should be considered if the clinical use of these cytokines is intended in this setting.
本研究的目的是探讨外周血干细胞（PBSC）动员及大剂量化疗（HDC）过程中血小板生成素（TPO）和Flt3配体（FL）的血清水平，并将这些数值与干细胞产量和植入情况进行关联。共纳入39例患者。通过化疗动员PBSC，随后给予两剂根据体表面积计算的糖基化重组人粒细胞集落刺激因子（rhu-G-CSF，来格司亭）。35例患者成功采集到PBSC，30例患者共接受了62个疗程的HDC（每位患者1 - 3个疗程）。对56例患者进行分析，在PBSC动员开始时、首次采集PBSC时、PBSC输注当天以及直至植入时均检测TPO和FL血清水平。TPO和FL血清基线平均水平分别为173 pg/ml和192 pg/ml，在开始采集PBSC时分别升至493和323 pg/ml。HDC 1后TPO最高值为2279 pg/ml，HDC 2后为2375 pg/ml，而HDC 1和HDC 2及PBSC输注后FL血清平均最高水平分别为1181和1236 pg/ml。PBSC动员开始时FL血清水平与CD34+细胞总产量相关（17.61±18.8×10(6)/kg体重，r = 0.81），而在PBSC输注后第11 - 13天TPO血清水平与输注的CD34+61+62+细胞量呈负相关（HDC 1和HDC 2时r分别为 - 0.88和 - 0.79）。TPO或FL血清水平与白细胞和血小板植入之间无强相关性。总之，化疗后给予糖基化rhu-G-CSF可使PBSC采集开始时血清TPO水平升高，FL水平升高程度较低。PBSC输注后TPO最大增幅为13.7倍，FL为6.4倍，表明内源性释放，如果在此情况下打算临床使用这些细胞因子，应予以考虑。
