中国组织工程研究

中国组织工程研究 ›› 2021, Vol. 25 ›› Issue (13): 2049-2054.doi: 10.3969/j.issn.2095-4344.3516

• 干细胞移植 stem cell transplantation • 上一篇    下一篇

同胞相合异基因造血干细胞移植联合非血缘脐血输注治疗重型再生障碍性贫血

韦中玲，蒋艺枝，黄来全，严家炜，余正芝，王娜娜，黄  辰，王  然，黄东平   

  1. 皖南医学院第一附属医院(弋矶山医院)血液科，安徽省芜湖市   241001
  • 收稿日期:2020-03-17 修回日期:2020-03-21 接受日期:2020-04-15 出版日期:2021-05-08 发布日期:2020-12-28
  • 通讯作者: 黄东平，主任医师，副教授，皖南医学院第一附属医院(弋矶山医院)血液科，安徽省芜湖市 241001
  • 作者简介:韦中玲，女，1979年生，安徽省芜湖市人，汉族，2008年皖南医学院毕业，硕士，副主任医师，主要从事恶性血液病诊治和造血干细胞移植治疗。 蒋艺枝，女，1987年生，安徽省芜湖市人，汉族，在读博士，住院医师，主要从事恶性血液病诊治和造血干细胞移植工作。
  • 基金资助:
    安徽省重点研究与开发项目(201904a07020036)，项目负责人：黄东平；皖南医学院重点培育项目(WK2018ZF09)，项目负责人：韦中玲；芜湖市科技计划项目(2019cg22)，项目负责人：韦中玲

Severe aplastic anemia treated with unrelated cord blood combined with matched sibling allogeneic hematopoietic stem cell transplantation

Wei Zhongling, Jiang Yizhi, Huang Laiquan, Yan Jiawei, Yu Zhengzhi, Wang Nana, Huang Chen, Wang Ran, Huang Dongping   

  1. Department of Hematology, First Affiliated Hospital (Yijishan Hospital) of Wannan Medical College, Wuhu 241001, Anhui Province, China
  • Received:2020-03-17 Revised:2020-03-21 Accepted:2020-04-15 Online:2021-05-08 Published:2020-12-28
  • Contact: Huang Dongping, Chief physician, Associate professor, Department of Hematology, First Affiliated Hospital (Yijishan Hospital) of Wannan Medical College, Wuhu 241001, Anhui Province, China
  • About author:Wei Zhongling, Master, Associate chief physician, Department of Hematology, First Affiliated Hospital (Yijishan Hospital) of Wannan Medical College, Wuhu 241001, Anhui Province, China Jiang Yizhi, Doctoral candidate, Resident physician, Department of Hematology, First Affiliated Hospital (Yijishan Hospital) of Wannan Medical College, Wuhu 241001, Anhui Province, China Wei Zhongling and Jiang Yizhi contributed equally to this paper.
  • Supported by:
    the Key Research and Development Project in Anhui Province, No. 201904a07020036 (to HDP); the Key Cultivation Project of Wannan Medical College, No. WK2018ZF09 (to WZL); the Wuhu Science and Technology Project, No. 2019cg22 (to WZL)

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摘要：

文题释义：
双重移植：是指同一种移植中的造血干细胞来源于2种不同类型的供体，其目的在于通过同时输注2种不同的移植物，既能快速获得造血重建，又能减轻急慢性移植物抗宿主病。
移植物抗宿主病：是异基因造血干细胞移植最常见的并发症，是受者抗原递呈细胞和供者成熟T细胞相互作用的结果。根据发病时间和临床表现分为急性移植物抗宿主病和慢性移植物抗宿主病。目前认为移植物中含有免疫活性细胞或成分、供受者之间存在组织不相容性、受者存在免疫耐受不能对移植物产生免疫应答、效应细胞迁移至靶器官是发生急性移植物抗宿主病的4个条件。

背景：同胞相合异基因造血干细胞移植目前仍然是治疗重型再生障碍性贫血的一线治疗方法，但是随着患者年龄增长，移植疗效明显下降。
目的：探讨同胞相合造血干细胞移植联合非血缘脐血输注治疗重型再生障碍性贫血的疗效以及安全性。
方法：纳入2017年7月至2018年2月在皖南医学院第一附属医院进行非血缘脐血联合同胞相合造血干细胞移植的4例重型再生障碍性贫血患者，对临床资料进行回顾性分析。
结果与结论：①4例患者均为男性，中位年龄为40岁，诊断至移植的中位时间为2.5个月；同胞供者采集骨髓及外周血干细胞，非血缘脐血采用单份，HLA配型≥4/6相合；②输注同胞供者干细胞中位总有核细胞为13.67×108/kg，中位CD34+细胞数为2.7×106/kg；输注非血缘脐血干细胞中位总有核细胞为2.1×107/kg，中位CD34+细胞数为1.21×105/kg；③移植后中性粒细胞和血小板中位植入时间分别为+10 d、+20 d；④移植后1例患者为同胞供者嵌合，3例患者为双供者混合嵌合；至随访日，3例双供者混合嵌合患者中，1例转为非血缘脐血完全植入，1例转为同胞供者完全植入，1例患者出现供受者混合嵌合，因感染而放弃治疗；⑤1例发生Ⅱ度急性移植物抗宿主病；Ⅲ-Ⅳ度急性移植物抗宿主病及慢性移植物抗宿主病发生率均为0%；⑥2年的无病生存率和总生存率均为75%，无移植物抗宿主病无复发生存率为100%；⑦结果表明，同胞相合异基因造血干细胞移植联合非血缘脐血输注治疗年龄稍长重型再生障碍性贫血患者的移植物抗宿主病发生率低，疗效肯定，但2种供者干细胞的植入动力学值得进一步研究。

https://orcid.org/0000-0003-2750-7517(韦中玲)
中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 干细胞, 骨髓, 外周血, 脐血, 再生障碍性贫血, 同胞相合, 移植, 嵌合度

Abstract: BACKGROUND: Sibling matched allogeneic hematopoietic stem cell transplantation is still the first-line treatment for severe aplastic anemia. However, with the increase of patients’ age, the effect of transplantation decreases significantly.
OBJECTIVE: To explore the efficacy and safety of unrelated cord blood combined with matched sibling hematopoietic stem cell transplantation in the treatment of severe aplastic anemia. 
METHODS:  A total of four severe aplastic anemia patients who underwent unrelated cord blood combined with matched sibling hematopoietic stem cell transplantation in First Affiliated Hospital (Yijishan Hospital) of Wannan Medical College from July 2017 to February 2018 were enrolled and their clinical data were used for retrospective analysis. 
RESULTS AND CONCLUSION: (1) All the four patients were male. The median age was 40 years old and the median time from diagnosis to transplantation was 2.5 months. Bone marrow and peripheral blood stem cells from a sibling donor as well as a unit of unrelated cord blood with HLA matching ≥ 4/6 were applied. (2) The median stem cells of total nucleated cells and CD34+ were 13.67×108/kg and 2.7×106/kg of the sibling donor, 2.1×107/kg and 1.21×105/kg of the unrelated cord blood, respectively. (3) The median implantation time of neutrophils and platelets was +10 days and +20 days, respectively. (4) After transplantation, one patient was sibling donor chimerism while that of another three patients was double donors. At the follow-up date, among the three cases of mixed chimerism from two donors, one was completely implanted with unrelated cord blood; one was completely implanted with sibling donor; the third case had mixed chimerism with sibling donor and recipient giving up treatment because of infection. (5) Only one patient developed grade II acute graft versus host disease. The incidence of III-IV acute graft versus host disease and chronic graft versus host disease was 0%. (6) Two-year post-transplant disease free survival and overall survival rates were both 75% and graft versus host disease-free and relapse-free survival was 100%. (7) The results show that sibling allogeneic hematopoietic stem cell transplantation combined with unrelated cord blood transfusion for the treatment of older patients with severe aplastic anemia has a low incidence of graft versus host disease and a positive effect, but the dynamics for the implantation of two kinds of donor stem cells is worthy of further study. 


Key words: stem cells, bone marrow, peripheral blood, cord blood, aplastic anemia, siblings, transplantation, chimerism

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