异基因造血干细胞移植后合并肾功能不全患者使用西罗莫司替代环孢素预防GVHD的临床分析  

Clinical analysis of sirolimus as an alternative GVHD prophylaxis for patients with kidney injury undergoing allo-HSCT

作　　者：孙葳 马瑞 何云[1] 柏露[1] 陈育红[1] 陈瑶[1] 张圆圆[1] 王景枝[1] 陈欢[1] 张晓辉[1] 许兰平[1] 王昱[1] 黄晓军[1] 孙于谦[1] Sun Wei;Ma Rui;He Yun;Bai Lu;Chen Yuhong;Chen Yao;Zhang Yuanyuan;Wang Jingzhi;Chen Huan;Zhang Xiaohui;Xu Lanping;Wang Yu;Huang Xiaojun;Sun Yuqian(Peking University People′s Hospital,Peking University Institute of Hematology,National Clinical Research Center for Hematologic Disease,Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation,Beijing 100044,China)

机构地区：[1]北京大学人民医院,北京大学血液病研究所,国家血液系统疾病临床医学研究中心,造血干细胞移植治疗血液病北京市重点实验室,北京100044

出　　处：《中华内科杂志》2023年第12期1444-1450,共7页Chinese Journal of Internal Medicine

基　　金：国家自然科学基金(8227010768);科技部重点研发计划(2021YFC2500300)。

摘　　要：目的初步探索在异基因造血干细胞移植(allo-HSCT)后合并肾功能不全患者中,使用西罗莫司替代环孢素预防移植物抗宿主病(GVHD)的可行性。方法回顾性病例系列研究。分析北京大学人民医院2008年8月1日至2022年10月31日行allo-HSCT,并因肾功能不全使用西罗莫司替代环孢素预防GVHD的11例患者,评估GVHD发生情况,以及肾功能、感染和血栓性微血管病发生情况。结果 11例患者中,单倍型相合移植6例,同胞全相合移植5例。开始使用西罗莫司的中位时间为移植后30 d(范围7~167 d),使用西罗莫司的中位疗程为52 d(范围9~120 d)。使用西罗莫司同时,1例未合并使用其他预防药物,6例同时联合霉酚酸酯(MMF)及CD25单抗,3例联合MMF,1例联合CD25单抗。11例使用西罗莫司预防GVHD患者中,2例患者发生Ⅲ度急性GVHD;9例患者肾功能恢复正常或改善;1例患者发生严重肺部感染并死亡;1例患者出现移植相关血栓性微血管病。11例患者中位随访时间130 d(范围54~819 d),非复发死亡1例,复发死亡1例。结论在因肾功能不全而不耐受环孢素的allo-HSCT患者中,基于西罗莫司的替代预防GVHD方案是一种潜在的可行选择,但其有效性及安全性仍需进一步优化及前瞻性研究验证。Objective To explore the feasibility of sirolimus as an alternative graft versus host disease(GVHD)prophylaxis in patients with kidney injury after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods Retrospective case series study.Medical records of 11 patients in Peking University People′s Hospital from 1 August 2008 to 31 October 2022,who received sirolimus instead of cyclosporine to prevent GVHD,due to renal insufficiency after allo-HSCT,were analyzed retrospectively.Incidence of GVHD,infection,and transplant-associated thrombotic microangiopathy(TA-TMA),as well as renal function,were evaluated.Results Among the 11 patients who received sirolimus,6 were treated with haploidentical donor HSCT,and 5 were treated using matched sibling donor HSCT.The median(range)time of sirolimus administration was 30(7-167)days after allo-HSCT,and the median(range)sirolimus course duration was 52(9-120)days.During sirolimus treatment,1 case did not undergo combined treatment with other prophylactic drugs,3 cases received combined mycophenolate mofetil(MMF),and 1 case underwent combined CD25 monoclonal antibody treatment,while 6 cases had combined therapy with both MMF and CD25 monoclonal antibody.Of the 11 patients,2 developed GradeⅢacute GVHD,1 developed severe pneumonia and died,and 1 developed TA-TMA,while nine patients had normal or improved renal function.Median(range)follow-up time was 130(54-819)days.Non-relapse mortality was observed in 1 patient.Relapse mortality was also observed in 1 patient.Conclusion Sirolimus-based alternative GVHD prophylaxis is a potentially viable option for patients undergoing allo-HSCT who cannot tolerate cyclosporine,but its efficacy and safety require further optimization and verification in prospective studies.

关 键 词：造血干细胞移植 西罗莫司 移植物抗宿主病 

分 类 号：R457.7[医药卫生—治疗学] R733[医药卫生—临床医学]