脐血间充质干细胞联合艾曲波帕治疗异基因造血干细胞移植后移植物功能不良的临床研究  

Clinical research of umbilical cord mesenchymal stem cells combined with eltrombopag for treatment of poor graft function following allogeneic hematopoietic stem cell transplantation

作　　者：薛松[1] 刘夫红 张永平 谭毅 王静波[1] Xue Song;Liu Fuhong;Zhang Yongping;Tan Yi;Wang Jingbo(Department of Hematology,Aerospace Center Hospital,Beijing 100049,China;Shandong Qilu Cell Therapy Engineering Technology Co.LTD,Jinan 250101,Shandong Province,China)

机构地区：[1]航天中心医院血液科,北京100049 [2]山东省齐鲁细胞治疗工程技术有限公司,济南250101

出　　处：《国际输血及血液学杂志》2022年第2期132-139,共8页International Journal of Blood Transfusion and Hematology

基　　金：首都临床特色应用研究与成果推广(Z171100001017103)。

摘　　要：目的探讨脐血间充质干细胞(MSC)联合艾曲波帕治疗异基因造血干细胞移植(allo-HSCT)后移植物功能不良(PGF)患者的疗效及安全性。方法选择2018年3月至2019年6月,在航天中心医院血液科接受allo-HSCT后,发生PGF的6例患者为研究对象。其中,男性患者为5例,女性为1例;患者中位年龄为33岁(范围:16~45岁)。根据血常规、骨髓细胞形态学、免疫表型及DNA指纹图谱等检查结果,患者被确诊为PGF。采用脐血MSC(1×10^(6)/kg)联合艾曲波帕(25~75 mg/d)对患者进行治疗。本研究对患者的随访截至2020年3月1日。回顾性分析患者的临床资料、相关实验室检查结果、脐血MSC联合艾曲波帕治疗PGF患者的临床疗效、不良反应及预后。本研究获得航天中心医院医学伦理委员会批准(批准号:20160420-XYZZ-02),并与全部患者签署临床研究知情同意书。结果①本组6例患者的原发疾病中,急性髓细胞白血病(AML)为2例,肝脾T细胞淋巴瘤(HSTCL)为1例,T淋巴母细胞淋巴瘤/白血病(T-LBC/ALL)为2例,慢性粒单核细胞白血病(CMML)为1例。所有6例患者移植前均处于未缓解状态。allo-HSCT后,均获造血功能重建,粒细胞植入的中位时间为移植后13 d(范围:12~14 d),有4例患者治疗前血小板未植入,剩余2例患者血小板植入时间分别为移植后13 d及90 d,所有患者在移植后28 d经骨髓DNA指纹图谱证实为完全供者嵌合。6例患者中有5例发生急性移植物抗宿主病(aGVHD),均为Ⅲ~Ⅳ度aGVHD,经系统治疗后均获得良好控制。②患者的PGF中位诊断时间为移植后57 d(范围:28~370 d);其临床特征包括血常规检查结果示,2系或者3系血细胞计数持续减少,骨髓细胞形态学检查结果示骨髓增生减低或者明显减低,巨核细胞少见或者缺如,微小残留病(MRD)检查未见原发疾病复发证据。③患者输注脐血MSC的中位次数为3.5次(范围:2~4次)。治疗后,1例患者无效,5例有效,达治疗有效的�Objective To investigate efficacy and safety of umbilical cord mesenchymal stem cells(MSC)combined with eltrombopag in treatment of poor graft function(PGF)patients after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods From March 2018 to June 2019,six cases of patients who suffered from PGF after having received allo-HSCT in Department of Hematology,Aerospace Center Hospital,were selected as research subjects,including 5 males and 1 female with a median age of 33 years(rang:16-45 years).Patients were confirmed with PGF after blood routine examination,bone marrow cell morphology,immunophenotyping and DNA fingerprinting,etc..Patients were treated with umbilical cord MSC infusion(1×10^(6)/kg)in combination with eltrombopag(25-75 mg/d),and followed up to March 1,2020.Clinical data,relevant laboratory examination results,clinical efficacy,adverse reactions and prognosis of the patients treated with umbilical cord MSC combined with eltrombopag were retrospectively analyzed.The study was approved by Medical Ethics Committee of Aerospace Center Hospital(approval No.20160420-XYZZ-02),and informed consents were signed by all patients.Results①Among the 6 patients,there were 2 cases of acute myelocytic leukemia(AML),1 case of hepatosplenic T-cell lymphoma(HSTCL),2 cases of T-lymphoblastic lymphoma/leukemia(T-LBL/ALL),and 1 case of chronic myelomonocytic leukemia(CMML).All 6 patients were rated non-remission before transplantation.All patients realized hematopoietic reconstitution after allo-HSCT.Median time to granulocyte implantation was 13 d(rang:12-14 d)after transplantation.No platelet implantation prior to treatment was observed for 4 patients,and the time to platelet implantation was 13 d and 90 d after transplantation for the remaining 2 patients,respectively.All patients were confirmed as complete donor chimerism by bone marrow DNA fingerprinting at 28 d after transplantation.After transplantation,five of the six patients developed acute graft versus host disease(aGVHD)gradedⅢ-Ⅳ,which was

关 键 词：间充质干细胞 造血干细胞移植 脐血 艾曲波帕 移植物功能不良 

分 类 号：R457.7[医药卫生—治疗学]