低剂量抗胸腺细胞球蛋白在供、受者年龄均≥40岁恶性血液病同胞相合外周血干细胞移植中的应用  

Application of low-dose ATG for GVHD prophylaxis in patients undergoing PBSCT aged over forty years old

作　　者：梁晨 姜尔烈 姚剑峰 马巧玲 翟卫华 庞爱明 黄勇 魏嘉璘 冯四洲 韩明哲 Liang Chen;Jiang Erlie;Fao Jianfeng;Ma Qiaoling;Zhai Weihua;Pang Aiming;Huang Yong;Wei Jialin;Feng Sizhou;Han Mingzhe(Institute of Hematology ＆ Blood Diseases Hospital, Chinese Academy of Medical Sciences ＆ Peking Union Medical College, Tianjin 300020, Chin)

机构地区：[1]中国医学科学院、北京协和医学院血液病医院(血液学研究所),天津300020

出　　处：《中华血液学杂志》2018年第4期292-298,共7页Chinese Journal of Hematology

基　　金：国家自然科学基金（81670171）

摘　　要：目的探讨在供、受者年龄均≥40岁同胞相合外周血干细胞移植（MSD—PBSCT）移植物抗宿主病（GVHD）预防方案中增加低剂量抗胸腺细胞球蛋白（ATG）的效果。方法回顾性分析2013年3月至2017年4月行MSD—PBSCT且供、受者年龄均≥40岁恶性血液病患者的临床资料。43例患者在常规急性GVHD预防方案（环孢素A或他克莫司联合短疗程甲氨蝶呤）中加入ATG1．5mg·kg^-1·d^-1×3d（ATG组），55例患者应用常规GVHD预防方案（对照组）。结果@ATG组中性粒细胞植入中位时间短于对照组[13（11～17）d对14（12～24）d，P=0．001]，血小板植入中位时间差异无统计学意义[14（11～43）d对15（11—42）d，P=0．071）]。②ATG组＋100d内急性GVHD累积发生率低于对照组[25．6％（95％CI13．7％～39-3％）对49．1％（95％C135．2％～61．6％），P=0．018]，Ⅱ～Ⅳ度急性GVHD、慢性GVHD发生率差异无统计学意义[18．6％（95％CI8．6％～31．5％）对23．6％（95％CI13．4％～35．6％），P=0．509；49．6％（95％CI31．6％～65.3％）对56．4％（95％C141．4％～69．0％），P=0．221]。@ATG组与对照组移植后1年巨细胞病毒血症累积发生率差异无统计学意义[21．1％（95％C110．3％～34．5％）对31．1％（95％C118．8％～44．2％），P=0．429]。④ATG组及对照组移植后2年累积复发率[24．0％（95％CI11．5％～38．9％）对24．0％（95％CI12．1％～38．2％），P=0．608]、非复发死亡率[10．2％（95％c，3．1％-22．1％）对21．6％（95％a9．4％～37．0％），P=0．411]及无病生存率[65．8％（95％a50．3％～81．3％）对54．4％（95％CI37．7％～71．1％），P=0．955]差异均无统计学意义，但ATG组移植后2年总生存率优于对照组[83．8％（95％C171．8％～90．0％）对58．0％（95％C142．2％～73．9％），P=0．019]。结论对于年龄较大的MSD—PBSCT患者，在常规GVHD预防方案�Objective To explore the effectiveness of a novel GVHD prophylaxis regimen containing low-dose anti-T lymphocyte globulin （ATG） in patients undergoing peripheral blood stem cell transplantation （PBSCT） from HLA-matched sibling donors （MSD） given both the patients and donors were aged over forty years old. Methods From March 2013 to April 2017, 98 patients with hematologic malignan- cies were enrolled in the study. Standard GVHD prophylaxis consisted of the administration of cyclosporine A/tacrolimus and a short course of methotrexate. In ATG group, 43 patients received low-dose rabbit ATG （Sanofi, 1.5 mg/kg per day for 3 consecutive days） before PBSCT. A retrospective matched-pair analysis was performed and 55 matched controls were available. The therapeutic process and clinical outcome were retrospectively analyzed. Results ①Neutrophil engraftment was achieved earlier in ATG group than the control one [ 13（11-17）d vs 14（12-24）d, P = 0.0011. The time to platelet engraftment was similar between the two groups [ 14（11-43）d vs 15（11-42）d, P = 0.0711. ②The cumulative incidence of aGVHD was significantly lower in ATG group [ 25.6% （95% CI 13.7%- 39.3%） vs 49.1% （95% C135.2%-61.6%）, P = 0.0181. The incidences of grade II- IV aGVHD [ 18.6% （95%CI 8.6%-31.5%） vs 23.6% （95%CI 13.4%-35.6%）, P = 0.509 ] and cGVHD [49.6% （95% CI 31.6%- 65.3%） vs 56.4% （95% CI 41.4%- 69.0%）, P = 0.221 ] were not significantly different between the two groups. ③The 1-year cumulative incidence of CMV viremia was similar between the two groups [ 21.1%（95%CI 10.3%-34.5%） vs 31.1% （95%CI 18.8%-44.2%）, P = 0.429 ]. ④The cumulative incidences of disease relapse [24.0%（95%CI 11.5%-38.9%） vs 24.0% （95% CI 12.1%-38.2%）, P = 0.608） , non-relapse mortality [ 10.2% （95% CI 3.1%-22.1%） vs 21.6% （95%CI 9.4%-37.0%）, P = 0.411 ] and DFS [65.8% （95%CI 50.3%-81.3%） vs 54.4% （95%CI 37.7%-71.1%）, P = 0.9551 were comparable between the two groups. 2-year overall survi

关 键 词：抗胸腺细胞球蛋白 移植预处理 同胞相合供者 移植物抗宿主病 

分 类 号：R457.7[医药卫生—治疗学]