中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (19): 4911-4917.doi: 10.12307/2026.673

• 造血干细胞 hematopoietic stem cells • 上一篇    下一篇

异基因造血干细胞移植后非原发病浸润相关中枢神经系统疾病的回顾性分析

陈诗彧,张晓瀚,李晓清,杜  新   

  1. 深圳大学第一附属医院/深圳市第二人民医院血液内科,广东省深圳市  518035
  • 收稿日期:2025-05-16 接受日期:2025-09-10 出版日期:2026-07-08 发布日期:2026-02-14
  • 通讯作者: 杜新,博士,主任医师,深圳大学第一附属医院/深圳市第二人民医院血液内科,广东省深圳市 518035
  • 作者简介:陈诗彧,女,1991年生,汉族,2017年郑州大学第一附属医院毕业,硕士,主治医师,主要从事恶性血液病及造血干细胞移植研究。
  • 基金资助:
    深圳市重点学科(SZXK008),学科带头人:杜新

Retrospective analysis of central nervous system diseases related to non-primary infiltration after allogeneic hematopoietic stem cell transplantation

Chen Shiyu, Zhang Xiaohan, Li Xiaoqing, Du Xin   

  1. Department of Hematology, The First Affiliated Hospital of Shenzhen University/Shenzhen Second People's Hospital, Shenzhen 518035, Guangdong Province, China
  • Received:2025-05-16 Accepted:2025-09-10 Online:2026-07-08 Published:2026-02-14
  • Contact: Du Xin, PhD, Chief physician, Department of Hematology, The First Affiliated Hospital of Shenzhen University/Shenzhen Second People's Hospital, Shenzhen 518035, Guangdong Province, China
  • About author:Chen Shiyu, MS, Attending physician, Department of Hematology, The First Affiliated Hospital of Shenzhen University/Shenzhen Second People's Hospital, Shenzhen 518035, Guangdong Province, China
  • Supported by:
    Shenzhen Key Medical Discipline Construction Fund, No. SZXK008 (to DX)

摘要:

文题释义:

异基因造血干细胞移植:是指将健康供者的造血干细胞移植到患有血液病的患者体内,以重建其造血和免疫系统的治疗方法。此研究纳入的298例患者中,移植类型包括单倍体移植、同胞全相合移植和非血缘全相合移植。
非原发病浸润相关中枢神经系统疾病:是异基因造血干细胞移植后并发症之一,其发病机制复杂,涉及药物毒性、感染等多种因素。文中分析显示,中位发病时间为移植后16 d(2-45 d),主要症状包括抽搐、血压升高、头痛及意识障碍;植入延迟、中枢神经系统白血病病史及移植物抗宿主病是发病的危险因素;病因包括:钙调磷酸酶抑制剂相关脑病、中枢神经系统感染、血栓性微血管病及颅内出血等。

摘要
背景:异基因造血干细胞移植后可合并非原发病浸润相关中枢神经系统疾病的并发症,其临床症状、可能的发病原因及预后目前尚未有明确的定论。
目的:探讨异基因造血干细胞移植后非原发病浸润中枢神经系统疾病的临床特征、危险因素及预后,以期为临床早期诊断、病因干预及预后改善提供循证依据。
方法:回顾性分析2015年1月至2024年6月期间298例血液病患者在异基因造血干细胞移植后发生非原发病浸润中枢神经系统疾病的临床资料、实验室特征及治疗过程,分为非原发病浸润中枢神经系统疾病组(n=19)和对照组(未发生非原发病浸润中枢神经系统疾病,n=279),通过统计学方法对发病原因进行危险因素分析,对发病患者的临床症状、可能的发病原因及预后进行评估。
结果与结论:①298例接受异基因造血干细胞移植患者中,有19例发生非原发病浸润中枢神经系统疾病,发病率为6.4%;②发病的中位时间为移植后16 d(2-45 d),患者主要以抽搐作为首发症状,同时伴随血压升高、头痛、视力下降、意识障碍及精神行为异常等表现;③单因素分析显示,粒系植入时间、血小板植入时间、移植前中枢神经系统白血病病史以及Ⅲ-Ⅳ度移植物抗宿主病的发生与非原发病浸润中枢神经系统疾病的发病存在显著关联,具体病因分析结果显示:钙调磷酸酶抑制剂相关脑病2例,中枢神经系统损伤4例,中枢神经系统感染4例,移植相关血栓性微血管病4例,中枢神经系统移植物抗宿主病1例,颅内出血2例,内分泌代谢相关脑病1例,病因不明1例;④截至随访日期,19例异基因造血干细胞移植后出现非原发病浸润中枢神经系统疾病患者的累计死亡率为47%(9/19),显著高于对照组的累计死亡率28.6%(80/279);进一步分析显示,非原发病浸润中枢神经系统疾病组患者移植后1年和2年的预计总生存率均显著低于对照组。总之,异基因造血干细胞移植后非原发病浸润中枢神经系统疾病由多种移植相关因素共同引发,及时识别致病因素并进行精准的诊断与治疗,对改善移植相关非原发病浸润中枢神经系统并发症患者的预后至关重要。

关键词: 异基因造血干细胞移植(Allo-HSCT), 非原发病浸润中枢神经系统疾病(NPI-CNS), 移植物抗宿主病(GVHD), 血栓性微血管病(TMA), 钙调磷酸酶抑制剂相关脑病, 中枢神经系统感染, 可逆性后部脑病综合征(PRES), 中枢神经系统白血病(CNSL)

Abstract: BACKGROUND: Allogeneic hematopoietic stem cells may be transplanted with complications of the central nervous system that are not related to primary disease infiltration. There is no clear conclusion on the clinical symptoms, possible causes, and prognosis.
OBJECTIVE: To explore the clinical characteristics, risk factors, and prognosis of complications related to non-primary infiltration of central nervous system after allogeneic hematopoietic stem cell transplantation, in order to provide evidence-based basis for early clinical diagnosis, etiological intervention, and prognosis improvement.
METHODS: The clinical data, laboratory characteristics, and treatment process of 298 hematopathy patients with non-primary infiltration-related central nervous system complications after allogeneic hematopoietic stem cell transplantation from January 2015 to June 2024 were retrospectively analyzed. They were divided into the non-primary infiltration-related central nervous system complication group (n=19) and the control group (no non-primary infiltration-related central nervous system complications, n=279). The risk factor analysis was carried out through statistical methods. The clinical symptoms, possible causes of the disease, and prognosis of the patients were evaluated. 
RESULTS AND CONCLUSION: (1) Among the 298 patients undergoing allogeneic hematopoietic stem cell transplantation, 19 cases experienced central nervous system complications related to non-primary infiltration, with an incidence rate of 6.4%. (2) The median time of onset was 16 days after transplantation (2-45 days). Patients mainly use convulsions as the first symptom, accompanied by increased blood pressure, headache, vision loss, consciousness disorders, and mental behavior abnormalities. (3) Univariate analysis showed that the time of granule implantation, platelet implantation time, history of central nervous system leukemia before transplantation, and the occurrence of graft-versus-host disease in degree III-IV were significantly associated with the incidence of central nervous system complications related to non-primary infiltration. The results of specific etiology analysis show that 2 cases of calcitric acid inhibitor-related encephalopathy, 4 cases of central nervous system damage, 4 cases of central nervous system infection, 4 cases of transplant-related thrombotic microvascular disease, 1 case of graft-versus-host disease in the central nervous system, 2 cases of intracranial hemorrhage, 1 case of endocrine and metabolism-related encephalopathy, and 1 case of unknown cause. (4) As of the follow-up date, the cumulative mortality rate of 19 patients with non-primary infiltration-related central nervous system complications after allogeneic hematopoietic stem cell transplant was 47% (9/19), which was significantly higher than the cumulative mortality rate of 28.6% (80/279) in the control group. Further analysis showed that the expected overall survival rates of patients with the non-primary infiltration-related central nervous system complication group were significantly lower than those of the control group. In short, the central nervous system complications related to non-primary infiltration after allogeneic hematopoietic stem cell transplantation are a rare, difficult to diagnose and highly lethal acute central nervous system disease, which is caused by a variety of transplant-related factors. Timely identification of pathogenic factors and accurate diagnosis and treatment is crucial to improve the prognosis of patients with transplant-related non-primary infiltration of central nervous system complications.

Key words: allogeneic hematopoietic stem cell transplantation (Allo-HSCT), non-primary infiltrating central nervous system disease (NPI-CNS), graft-versus-host disease (GVHD), thrombotic microangiopathy (TMA), calcineurin inhibitor-associated encephalopathy, central nervous system infection, posterior reversible encephalopathy syndrome (PRES), central nervous system leukemia (CNSL)

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