氟达拉滨联合后置环磷酰胺用于单倍体造血干细胞移植临床疗效分析  

Clinical analysis of the effect of fludarabine combined with post-transplantation cyclophosphamide in haploid hematopoietic stem cell transplantation

作　　者：王甜甜[1] 曹俊杰[1] 刘旭辉[1] 裴仁治[1] 陆滢[1] WANG Tiantian;CAO Junjie;LIU Xuhui;PEI Renzhi;LU Ying(Department of Hematology,the Affiliated People's Hospital of Medical College of Ningbo University,Ningbo 315040,Zhejiang,China)

机构地区：[1]宁波大学附属人民医院血液科,浙江宁波315040

出　　处：《中国临床药理学与治疗学》2022年第3期295-301,共7页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：浙江省医药卫生科技计划项目(2017KY144);宁波市鄞州区农业与社会发展科技项目(2019YZQ010001)。

摘　　要：目的:探讨氟达拉滨(Flu)联合后置环磷酰胺(CTX)预防单倍体造血干细胞移植中移植物抗宿主病(GVHD)的治疗方法。方法:29例患者接受常规BUCY-ATG预处理方案。52例患者接受PTCy(Flu+BUCY+后置CTX预处理)方案(CTX 50 mg/kg,+3 d及+4 d)。结果:中位随访时间为359 d,所有患者在第+30,+60天短串联重复序列(STR DNA)检测达到完全供体嵌合。PTCy组和BUCY-ATG组中性粒细胞计数≥0.5×10^(9)/L和血小板计数≥20×10^(9)/L的中位时间分别为(11.5 vs.12)d和(12 vs.13)d,Ⅱ~Ⅳ度急性GVHD(aGVHD)、Ⅲ~Ⅳ度aGVHD和慢性GVHD的累计发生率分别为(30.8%vs.31%)、(19.2%vs.24.1%)和(5.8%vs.24.1%)。累计总生存率(OS)和无病生存率(DFS)为65.5%vs.62.1%,1年时的非复发死亡率(NRM)为75%和77%。巨细胞病毒(CMV)感染和EB病毒(EBV)感染的发生率分别为(48.3%vs.50%)和(6.9%vs.3.7%)。结论:在缺乏HLA配型相合同胞供者和非亲缘全和供者的情况下,后置CTX的单倍体造血干细胞移植不失为一种较好的选择。但移植后的复发和感染仍然是影响患者长期存活的不良因素,寻找合适的移植方案仍然是当务之急。AIM:To investigate the therapeutic method of fludarabine combined with subsequent cyclophosphamide in the prevention of GVHD in haploid hematopoietic stem cell transplantation.METHODS:A total of 52 patients receiving PTCY(50 mg/kg,on days 3 and 4)were matched with 29 patients receiving ATG.RESULTS:The median follow-up time was 359 days.Complete donor chimerism was achieved in all patients by STR DNA detection on days+30,+60.The median time to neutrophils≥0.5×10^(9)/L and platelets≥20×10^(9)/L were(11.5 vs.12)days and(12 vs.13)days respectively,between PTCy group and ATG group,The cumulative incidence of grade II-IV acute GVHD(aGVHD),gradeⅢ-IV aGVHD,and chronic GVHD were(30.8%vs.31%),(19.2%vs.24.1%)and(5.8%vs.24.1%)respectively.The cumulative overall survival(OS)and disease-free survival(DFS)were 65.5%vs.62.1%,the non-relapse-mortality(NRM)at 1 years were 75%and 77%.Incidence of CMV infection and EBV infection were(48.3%vs.50%)and(6.9%vs.3.7%).CONCLUSION:HLA-haploidentical HSCT with PTCy is a viable option when lack of HLA matched sibling and unrelated donors.The rate of severe GVHD is acceptable.But post-transplant relapse and infection still are major hinder,and the protocol should be modified.

关 键 词：抗胸腺细胞球蛋白(ATG) 移植后大剂量环胺(PTCy) 单倍体 移植物抗宿主病(GVHD) 造血干细胞移植 

分 类 号：R457.1[医药卫生—治疗学] R552[医药卫生—临床医学]