来格司亭联合地塞米松用于中性粒细胞动员和采集的剂量反应分析。

A dose-response analysis of lenograstim plus dexamethasone for neutrophil mobilization and collection.

作者信息

Heuft Hans-Gert, Goudeva Lilia, Pulver Nicole, Grigull Lorenz, Schwella Nimrod, Blasczyk Rainer

机构信息

Department of Transfusion Medicine, Hannover Medical School, Hannover, Germany.

出版信息

Transfusion. 2005 Apr;45(4):604-12. doi: 10.1111/j.0041-1132.2005.04240.x.

DOI:10.1111/j.0041-1132.2005.04240.x

PMID:15819683

Abstract

BACKGROUND

The objective was to evaluate the dose-response relationship of lenograstim plus dexamethasone for neutrophil mobilization and collection.

STUDY DESIGN AND METHODS

In a prospective study, 260 healthy volunteers received oral dexamethasone (8 mg) plus a single subcutaneous injection of glycosylated granulocyte-colony-stimulating factor (G-CSF; lenograstim) at medians of 1.5 (1.0-2.3) microg per kg (n = 43), 3 (2.4-4.1) microg per kg (n = 73), 6 (4.3-7.9) microg per kg (n = 123), and 12 (8.2-17.2) microg per kg (n = 21) and underwent neutrophil collections with a polymorphonucleated neutrophil (PMN) program. White blood cell (WBC) counts and PMN mobilization and collection results were compared, and the severity and clinical significance of donor adverse reactions were evaluated. Fifty-two neutropenic patients (29 children, 23 adults) underwent 271 neutrophil transfusions (GTXs) every other day to maintain WBC levels continuously above 0.5 x 10(9) per L.

RESULTS

Within the dose range 1.5, 3, and 6 microg per kg, each doubling step was associated with a 10 to 15 percent PMN increase in peripheral blood up to 32.8 (19.1-49.2) x 10(9) per L (6 microg/kg; p </= 0.00032) as well as in the neutrophil concentrate up to 79 (34-150) x 10(9) per U (6 microg/kg; p </= 0.00042). A further doubling to 12 microg per kg achieved neither better mobilization nor better apheresis results. The rate of clinically important adverse reactions increased already with the 6 microg per kg mobilization step. The GTX resulted in median peak WBC increments to 3.8 (0.4-18.2) x 10(9) per L (children) and 1.6 (0.3-9.4) x 10(9) per L (adults), but in adults the WBC threshold of 0.5 x 10(9) per L was not continuously exceeded.

CONCLUSIONS

The most effective dose-response ratio for PMN mobilization was demonstrated in the 6 microg per kg lenograstim group. In neutropenic adults, GTX treatment on an every-other-day schedule may be ineffective.

摘要

背景

目的是评估来格司亭联合地塞米松用于中性粒细胞动员和采集的剂量反应关系。

研究设计与方法

在一项前瞻性研究中，260名健康志愿者接受口服地塞米松（8毫克）加单次皮下注射糖基化粒细胞集落刺激因子（G-CSF；来格司亭），剂量中位数分别为每千克1.5（1.0 - 2.3）微克（n = 43）、3（2.4 - 4.1）微克/千克（n = 73）、6（4.3 - 7.9）微克/千克（n = 123）和12（8.2 - 17.2）微克/千克（n = 21），并通过多形核中性粒细胞（PMN）程序进行中性粒细胞采集。比较白细胞（WBC）计数、PMN动员和采集结果，并评估供体不良反应的严重程度和临床意义。52名中性粒细胞减少患者（29名儿童，23名成人）每隔一天接受271次中性粒细胞输注（GTX），以持续维持白细胞水平高于每升0.5×10⁹。

结果

在每千克1.5、3和6微克的剂量范围内，每增加一倍剂量，外周血中的PMN增加10%至15%，最高可达每升32.8（19.1 - 49.2）×10⁹（6微克/千克；p≤0.00032），中性粒细胞浓缩物中最高可达每单位79（34 - 150）×10⁹（6微克/千克；p≤0.00042）。进一步增加到每千克12微克既未实现更好的动员效果，也未获得更好的单采结果。在每千克6微克的动员剂量时，具有临床意义的不良反应发生率就已增加。GTX使儿童的白细胞峰值中位数增加到每升3.8（0.4 - 18.2）×10⁹，成人增加到每升1.6（0.3 - 9.4）×10⁹，但在成人中白细胞阈值每升0.5×10⁹未持续被超过。