PEG-rhG-CSF在71例allo-HSCT健康供者HSC动员中的有效性及安全性分析

Efficacy and Safety of PEG-rhG-CSF in HSC Mobilization in 71 Normal Healthy Donors for Allogeneic Hematopoietic Stem Cell Transplantation

目的:回顾性分析聚乙二醇化重组人粒细胞集落刺激因子(PEG-rhG-CSF)在71例异基因造血干细胞移植(allo-HSCT)健康供者造血干细胞(HSC)动员中的有效性及安全性。方法:选择2018年3月至2019年7月在西部战区总医院接受allo-HSCT的HSC供者71例,采用PEG-rhG-CSF 12 mg单次皮下注射,d 4检测CD34^(+)细胞数,根据细胞数于d 4或d 5采集干细胞。采集成功标准为CD34^(+)细胞≥2×10^(6)/kg,采集优良标准为CD34^(+)细胞≥4×10^(6)/kg。观察供者不良反应,评估供者的采集时间、采集成功率、采集优良率和采集次数,评估受者输入的细胞数、植入率、植活时间及急性移植物抗宿主病(a GVHD)发生率。结果:71例供者中男性39例,女性32例,中位年龄38(16-58)岁。动员d 4 CD34^(+)细胞中位数为46(7.4-133)/μl,其中39例CD34^(+)细胞≥40/μl于d 4采集,28例CD34^(+)细胞20-40/μl于d 5采集,4例CD34^(+)细胞<20/μl用rhG-CSF补救后d 5进行采集。65例采集1次,6例采集2次。采集的CD34^(+)细胞中位数为6.1(3.1-18.1)×10^(6)/kg。采集成功率为100%(71/71),采集优良率为81.6%(58/71)。71例供者均有不同程度肌肉及骨骼酸痛,17例(23.9%)出现头痛,11例(15.5%)出现乏力,3例(4.2%)出现低热。接受allo-HSCT的受者71例,输注的单个核细胞(MNC)中位数为8.3(5-23.3)×10^(8)/kg,CD34^(+)细胞和CD3^(+)细胞中位数分别为5.3(3.1-10.7)×10^(6)/kg和1.9(0.5-7.6)×10^(8)/kg。71例中稳定植入68例(95.8%),中性粒细胞植入中位时间11(8-19) d,血小板植入中位时间12(8-23) d。稳定植入的68例中发生Ⅱ-Ⅳ度a GVHD 15例(22%),Ⅲ-Ⅳ度a GVHD 3例(4.4%),2例(2.9%)因发生重症a GVHD死亡。结论:PEG-rhG-CSF注射液用于allo-HSCT供者动员有效且安全,用药方便,为HSC动员提供了更多选择。

Objective:To retrospectively analyze the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF) in hematopoietic stem cell mobilization in 71 normal healthy donors for allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:From March 2018 to July 2019,71 patients received allo-HSCT in The General Hospital of Western Theater Command were enrolled in the study,a single dose of PEG-rhG-CSF was injected subcutaneously at 12 mg to all the stem cell donors.After injection for 4 days,CD34^(+) cell number were detected,stem cells were collected on day 4 or 5 according to the CD34^(+) cell number.The successful collection criteria were CD34^(+) cells≥2×10^(6)/kg,and the excellent collection criteria were CD34^(+) cells ≥4×10^(6)/kg.The side effects after mobilization were observed and the collection time,the success rate,excellent rate,and times of the collection were evaluated in the donors,as well as the infused cell number,the engraftment rate,the time of engraftment,and the incidence of acute graft-versus-host disease(aGVHD) of the recipients.Results:Seventy-one healthy stem cell donors included 39 males and 32 females with a median age of 38(16-58) years old.The median number of CD34^(+) cells on day 4 was 46(7.4-133)/μl,of which 39 cases with CD34^(+) cells≥40/μl were collected on day 4,28 cases with CD34^(+) cells 20-40/μl were collected on day 5,and 4 cases with CD34^(+) cells <20/μl were collected on day 5 after a salvage treatment with rhG-CSF.Sixty-five cases were collected once,while 6 cases twice.The median number of collected CD34^(+) cells was 6.1(3.1-18.1)×10^(6)/kg.The success collection rate was 100%(71/71),and the excellent collection rate was 81.6%(58/71).All the cases had varying degrees of muscle and bone soreness,17 cases(23.9%) had headache,11 cases(15.5%) had fatigue,and 3 cases(4.2%) had a mild fever.Among 71 recipients,the median number of infused mononuclear cells(MNC) was 8.3(5-23.3)×10^(8)/kg,the median number of infused CD34^(+) cells and CD3^(+) cells was 5.3(3.1-10.7)×10^(6)/kg and 1.9(0.5-7.6)×10^(8)/kg,respectively.Among them,68 cases(95.8%) had a stable engraftment,the median time of neutrophil engraftment was11(8-19) days,and the median time of platelet engraftment was 12(8-23) days.Among the 68 cases who were engrafted,15 cases(22%) had grade Ⅱ-Ⅳ aGVHD,including grade Ⅲ-Ⅳ aGVHD in 3 patients(4.4%),2 cases(2.9%) died of severe aGVHD.Conclusion:For allo-HSCT donor mobilization,PEG-rh-G-CSF is effective,safe,and convenient,providing more options for HSC mobilization.