摘要
目的探讨经进一步改良的白舒非(BU)/环磷酰胺(CY)+兔抗胸腺细胞球蛋白(ATG)移植预处理方案在亲缘间单倍体相合外周血造血干细胞移植治疗重型再生障碍性贫血(SAA)临床应用中的安全性及有效性。方法华北理工大学附属医院2009年7月-2019年7月的26例SAA患者,以亲缘间单倍体相合外周血造血干细胞移植预处理方案(以改良BU/CY+ATG单倍体移植治疗SAA的“北京方案”为基础并对其进一步改良)进行治疗。①依据SAA患者移植前骨髓活检造血组织容量不同制定相应的清理残留造血细胞的方法。骨髓活检提示骨髓造血组织容量<10%时,以改良BU/CY+ATG的“北京方案”进行预处理;10%≤骨髓造血组织容量≤25%时,在原方案基础上加用1d的BU用量,即将BU剂量提高至9.6 mg/kg(分3d静脉滴注),成为进一步改良的BU/CY+ATG移植预处理方案。②依据疾病诊断不同制定相应的移植预处理方案:SAA-阵发性睡眠性血红蛋白尿(SAA-PNH)综合征或单纯PNH患者直接采用将BU剂量定为9.6 mg/kg(分3d静脉滴注)的进一步改良的BU/CY+ATG移植预处理方案。移植方式:在“北京方案”骨髓+外周血造血干细胞移植的基础上改良为单纯外周血造血干细胞移植。结果26例SAA患者中,获得造血重建22例。随访至2019年12月,中位随访期48(5~122)个月,死亡5例,其中移植相关死亡4例(15.4%,4/26),中枢神经系统感染死亡1例(3.8%,1/26)。全组3年总生存率(OSR)84.2%,3年无进展生存率(PFS)72.6%(其中SAAⅠ:100.0%;SAA-PNH:100.0%;SAAⅡ:72.2%)。结论经进一步改良的BU/CY+ATG移植预处理方案在SAA单倍体外周血干细胞移植治疗中安全有效,不仅适用于SAAⅠ、SAAⅡ,同时适用于合并PNH克隆的SAA患者,值得临床推广应用。
Objective To evaluate the safety and efficacy of an further optimized pretreatment protocol for the treatment of severe aplastic anemia(SAA)by haploidentical peripheral hematopoietic stem cell transplantation.Methods From July 2009 to July 2019,26 SAA patients in the Affiliated Hospital of North China University of Technology were treated with haploidentical peripheral blood stem cell transplantation.The"Beijing protocol"of haploid transplantation for treating SAA is modified busulfan(BU)/cyclophosphamide(CY)+rabbit anti thymocyte globulin(ATG)regimen.We based on it and further refined it.Here's how it works:(1)According to the different volumes of hematopoietic tissue in bone marrow biopsy before transplantation,different methods for clearance of residual hematopoietic cells were established in SAA patients.If bone marrow hematopoietic tissue volume<10%,the bone marrow was pretreated with Beijing protocol of BU/CY+ATG.If 10%≤bone marrow hematopoietic tissue volume≤25%,the dose of BU for 1 day was added on the basis of the original protocol:Increase the dose of BU to 9.6 mg/kg(intravenous drip in 3 days),which became a modified BU/CY+ATG transplantation preconditioning protocol.(2)According to the diagnosis of the disease,the transplantation pretreatment was designed:Patients with SAA-PNH syndrome or with PNH alone were treated with further modified BU/CY+ATG transplantation preconditioning protocol,and the BU dose was set as 9.6 mg/kg(intravenous drip in 3 days).Transplantation way:The"Beijing protocol"is use of bone marrow plus peripheral blood hematopoietic stem cell.Based on it,the protocol was modified to simple peripheral blood hematopoietic stem cell transplantation.Results 22 of 26 SAA patients underwent hematopoietic reconstruction.The patients were followed up until December 2019,and the results were as follows:During a median follow-up period of 48(5-122)months,5 patients died,4 of whom suffered transplant-related deaths(15.4%,4/26),and 1 of whom was due to central nervous system infection(3.8%,1/26).The 3-year overall survival rate(OSR)was 84.2%,the 3-year progression-free survival(PFS)was 72.6%(SAA I:100.0%,SAA-PNH:100.0%,SAA II:72.2%).Conclusions The further improved BU/CY+ATG transplantation preconditioning scheme is safe and effective in SAA with haploid peripheral blood stem cell transplantation.It is suitable not only for SAA I,SAA II,but also for patients with PNH clone,thus being worth wider clinical aplplication.
作者
冯术青
薛慧
王翠民
姚艳红
史月
刘志彬
高峰
Feng Shu-Qing;Xue Hui;Wang Cui-Min;Yao Yan-Hong;Shi Yue;Liu Zhi-Bin;Gao Feng(Department of Hematology,Affiliated Hospital of North China University of Technology,Tangshan,Hebei 063000,China;Department of Blood Transfusion,Affiliated Hospital of North China University of Technology,Tangshan,Hebei 063000,China)
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2020年第9期962-966,共5页
Medical Journal of Chinese People's Liberation Army
基金
中国煤炭工业协会科学技术研究项目(MTKJ2018-268)
河北省医学适用技术跟踪项目(G2018060)
河北省医学科学研究课题(20191115)。
关键词
重型再生障碍性贫血
单倍型
外周血
造血干细胞移植
预处理方案
severe aplastic anemia
haploid
peripheral blood
hematopoietic stem cell transplantation
conditioning regimen
