Kuter D J, Goodnough L T, Romo J, DiPersio J, Peterson R, Tomita D, Sheridan W, McCullough J
Hematology/Oncology Unit, Massachusetts General Hospital, Boston 02114, USA.
Blood. 2001 Sep 1;98(5):1339-45. doi: 10.1182/blood.v98.5.1339.
The recombinant thrombopoietins have been shown to be effective stimulators of platelet production in cancer patients. It was therefore of interest to determine if one of these, pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), could be used to increase platelet counts and consequently platelet yields from apheresis in healthy platelet donors. In a blinded, 2-cycle, crossover study, 59 platelet donors were randomized to receive a single subcutaneous injection of PEG-rHuMGDF (1 microg/kg or 3 microg/kg) or placebo and 15 days later undergo platelet apheresis. Donors treated with placebo had a median peak platelet count after PEG-rHuMGDF injection of 248 x 10(9)/L compared with 366 x 10(9)/L in donors treated with 1 microg/kg PEG-rHuMGDF and 602 x 10(9)/L in donors treated with 3 microg/kg PEG-rHuMGDF. The median maximum percentage that platelet counts increased from baseline was 10% in donors who received placebo compared with 70% in donors who received 1 microg/kg and 167% in donors who received 3 microg/kg PEG-rHuMGDF. There was a direct relationship between the platelet yield and the preapheresis platelet count: Placebo-treated donors provided 3.8 x 10(11) (range 1.3 x 10(11)-7.9 x 10(11)) platelets compared with 5.6 x 10(11) (range 2.6 x 10(11)-12.5 x 10(11)) or 11.0 x 10(11) (range 7.1 x 10(11)-18.3 x 10(11)) in donors treated with 1 microg/kg or 3 microg/kg PEG-rHuMGDF, respectively. Substandard collections (<3 x 10(11) platelets) were obtained from 26%, 4%, and 0% of the placebo, 1 microg/kg, and 3 microg/kg donors, respectively. No serious adverse events were reported; nor were there events that met the criteria for dose-limiting toxicity. Thrombopoietin therapy can increase platelet counts in healthy donors to provide a median 3-fold more apheresis platelets compared with untreated donors.
重组血小板生成素已被证明是癌症患者血小板生成的有效刺激剂。因此，确定其中一种，即聚乙二醇化重组人巨核细胞生长和发育因子（PEG-rHuMGDF），是否可用于增加健康血小板供体的血小板计数，从而提高单采血小板的产量，是很有意义的。在一项双盲、两周期、交叉研究中，59名血小板供体被随机分为接受单次皮下注射PEG-rHuMGDF（1微克/千克或3微克/千克）或安慰剂，并在15天后进行血小板单采。接受安慰剂治疗的供体在注射PEG-rHuMGDF后的血小板计数峰值中位数为248×10⁹/L，而接受1微克/千克PEG-rHuMGDF治疗的供体为366×10⁹/L，接受3微克/千克PEG-rHuMGDF治疗的供体为602×10⁹/L。血小板计数从基线增加的最大百分比中位数在接受安慰剂的供体中为10%，而在接受1微克/千克的供体中为70%，在接受3微克/千克PEG-rHuMGDF的供体中为167%。血小板产量与单采前血小板计数之间存在直接关系：接受安慰剂治疗的供体提供了3.8×10¹¹（范围为1.3×10¹¹ - 7.9×10¹¹）个血小板，而接受1微克/千克或3微克/千克PEG-rHuMGDF治疗的供体分别提供了5.6×10¹¹（范围为2.6×10¹¹ - 12.5×10¹¹）或11.0×10¹¹（范围为7.1×10¹¹ - 18.3×10¹¹）个血小板。分别从26%、4%和0%的接受安慰剂、1微克/千克和3微克/千克治疗的供体中获得了不合格的采集量（<3×10¹¹个血小板）。未报告严重不良事件；也没有符合剂量限制性毒性标准的事件。血小板生成素治疗可增加健康供体的血小板计数，与未治疗的供体相比，单采血小板的中位数增加3倍。
