单倍体造血干细胞移植TBF方案预处理的安全性和有效性研究  

Safety and efficacy of TBF pretreatment during haploid hematopoietic stem cell transplantation

作　　者：朱文娟[1] 周士源[1] 马超 朱倩 李静[1] 马骁[1] 吴德沛[1] 吴小津[1] Zhu Wenjuan;Zhou Shiyuan;Ma Chao;Zhu Qian;Li Jing;Ma Xiao;Wu Depei;Wu Xiaojin(Department of Hematology,The First Affiliated Hospital of Soochow University,National Clinical Research Center for Hematologic Diseases,Jiangsu Institute of Hematology,Suzhou 215000,China;Department of Hematology,Soochow Hopes hematologic Hospital,Suzhou 215000,China)

机构地区：[1]苏州大学附属第一医院血液科,国家血液系统疾病临床医学研究中心,江苏省血液研究所,苏州215000 [2]苏州弘慈血液病医院血液科,苏州215000

出　　处：《中华器官移植杂志》2024年第2期88-95,共8页Chinese Journal of Organ Transplantation

基　　金：国家重点研发计划(2019YFC0840604、2017YFA0104500);国家科技重大专项课题(2017ZX09304021);江苏省自然科学基金(BK20211070);苏州市卫生健康委科研项目(LCZX202101);苏州大学附属第一医院博习临床研究项目(BXLC007)。

摘　　要：目的探讨塞替哌、氟达拉滨联合白消安(TBF)的预处理方案用于单倍体造血干细胞移植的安全性及有效性。方法回顾性分析苏州大学附属第一医院和苏州弘慈血液病医院2020年至2023年期间行单倍体造血干细胞移植的574例受者资料,其中20例接受TBF预处理方案(TBF组),其余554例接受白消安+环磷酰胺(mBUCY)预处理方案,采用倾向性匹配方法,匹配比例为1:2,以疾病类型、受者年龄及受者性别作为匹配因素,最终筛选出40例mBUCY预处理方案的受者作为对照(mBUCY组)。根据Bearman评分标准评估TBF预处理相关毒性;与mBUCY组比较,观察TBF方案在预处理相关毒性,长期生存的安全性及有效性。结果TBF组20例受者预处理期间主要的并发症为I~Ⅱ级口腔黏膜炎和胃肠道症状,未发生严重的心血管不良事件。TBF组粒细胞系重建时间为11 d(9~14)d,mBUCY组时间为12 d(10~28)d,两组比较差异无统计学意义(P=0.2)。TBF组巨核细胞系重建时间为18 d(9~100)d,mBUCY组时间为20 d(11~100)d,两组比较差异无统计学意义(P=0.7)。TBF组100 dⅡ~Ⅳ度急性移植物抗宿主病(acute graft versus host disease,aGVHD)的发病率低于mBUCY组(5%比35%,P=0.01)。TBF组和mBUCY组受者的1年总存活率分别为68%和62%,差异无统计学意义(P=0.98),TBF组1年无复发无GVHD存活(graft-versus-host disease-free,relapse-free survival,GRFS)率优于mBUCY组,但差异无统计学意义(63%比37%,P=0.06)。结论TBF预处理方案在单倍体造血干细胞移植中应用毒性低,安全性较好。TBF预处理方案与mBUCY预处理相比,能减少移植后Ⅱ~Ⅳ度aGVHD发生,可能改善受者的GRFS。Objective To explore the safety and efficacy of TBF conditioning regimen of thiotepa,fludarabine and busulfan in haploidentical hematopoietic stem cell transplantation(haplo-HSCT)for recipients with hematological malignancies unsuitable for BUCY conditioning regimen(busulfan,cyclophosphamide&mBUCY).Method A retrospective analysis was conducted for 20 recipients with malignant hematologic diseases receiving TBF conditioning regimen before haplo-HSCT at Soochow Hopes Hematologic Hospital from January 2020 to December 2023.The regimen-related toxicity of TBF was assessed by the Bearman scoring criteria.For comparing the safety and efficacy of TBF conditioning regimen with mBUCY regimen,propensity score matching was performed in a ratio of 1:2 with disease type,patient age and gender as matching factors.Result Mild oral mucositis and gastrointestinal reaction were major side-effects without severe cardiac events.Median time to neutrophil and platelet engraftments in TBF group was 11 and 18 days with comparable engraftment in mBUCY group.TBF regimen had a significantly lower incidence of gradeⅡ-Ⅳacute graft-versus-host disease(aGVHD)than mBUCY at Day 100(5%vs 35%,P=0.01).No significant inter-group difference existed in overall survival(68%vs 62%,P=0.98)while 1-year incidence of graft-versus-host disease-free,relapse-free survival(GRFS)improved(63%vs 37%,P=0.06)in TBF group.Conclusion TBF is a promising conditioning regimen with low toxicity and decent safety for haplo-HSCT.TBF patients tend to have a lower incidence of gradeⅡ-ⅣaGVHD and better GRFS than mBUCY.

关 键 词：造血干细胞移植 单倍体造血干细胞移植 预处理 安全性 有效性 

分 类 号：R457.7[医药卫生—治疗学]