CAJ | 학술논문

目的探讨脑脊液中EB病毒(EBV)DNA载荷检测对异基因造血干细胞移植(HSCT)后EBV相关性中枢神经系统(CNS)疾病的发生与发展及疗效评估的意义.方法 2008年7月至2012年8月接受异基因HSCT的患者272例,其中38例诊断为EBV相关性疾病的患者和8例不明原因CNS表现的患者纳入前瞻性研究(实验组)；另以移植后10例血液EBV DNA阳性但无EBV相关性疾病的患者和5例血液EBV DNA阴性的患者(血小板＞50×109/L)作为阴性对照.采用实时定量聚合酶链反应方法检测血液和脑脊液中EBV DNA.确诊为EBV相关性CNS疾病者予利妥昔单抗或者利妥昔单抗联合化疗治疗.结果 38例EBV相关性疾病患者中有13例(34.2％)诊断为EBV相关性CNS疾病,8例不明原因CNS表现的患者中有1例(12.5％)确诊,而在阴性对照组中无一例确诊.确诊的14例中包括移植后淋巴细胞增殖性疾病(PTLD) 10例和脑或脊髓炎4例,其中除1例外,其他13例的血液EBV DNA均为阳性,而患者脑脊液中EBV DNA载荷高于血液中(P＜0.05).5例治疗有效者的血液和脑脊液中EBV DNA载荷随着疾病控制而下降；9例初始治疗无效者脑脊液中EBV DNA载荷随疾病发展而上升,但血液中EBV DNA载荷变化不一,其中2例静脉应用利妥昔单抗为基础治疗的患者其外周血EBV DNA载荷下降,但CNS表现进一步恶化,脑脊液中EBV DNA载荷上升,鞘内应用利妥昔单抗后疾病获得缓解,脑脊液EBV DNA载荷下降.结论脑脊液EBV DNA的检测对诊断发生于CNS中EBV相关性疾病十分重要,其载荷水平可用于EBV相关性CNS疾病的发生、发展及疗效的评估.
목적 탐토뇌척액중EB병독(EBV)DNA재하검측대이기인조혈간세포이식(HSCT)후EBV상관성중추신경계통(CNS)질병적발생여발전급료효평고적의의.방법 2008년7월지2012년8월접수이기인HSCT적환자272례,기중38례진단위EBV상관성질병적환자화8례불명원인CNS표현적환자납입전첨성연구(실험조)；령이이식후10례혈액EBV DNA양성단무EBV상관성질병적환자화5례혈액EBV DNA음성적환자(혈소판＞50×109/L)작위음성대조.채용실시정량취합매련반응방법검측혈액화뇌척액중EBV DNA.학진위EBV상관성CNS질병자여리타석단항혹자리타석단항연합화료치료.결과 38례EBV상관성질병환자중유13례(34.2％)진단위EBV상관성CNS질병,8례불명원인CNS표현적환자중유1례(12.5％)학진,이재음성대조조중무일례학진.학진적14례중포괄이식후림파세포증식성질병(PTLD) 10례화뇌혹척수염4례,기중제1예외,기타13례적혈액EBV DNA균위양성,이환자뇌척액중EBV DNA재하고우혈액중(P＜0.05).5례치료유효자적혈액화뇌척액중EBV DNA재하수착질병공제이하강；9례초시치료무효자뇌척액중EBV DNA재하수질병발전이상승,단혈액중EBV DNA재하변화불일,기중2례정맥응용리타석단항위기출치료적환자기외주혈EBV DNA재하하강,단CNS표현진일보악화,뇌척액중EBV DNA재하상승,초내응용리타석단항후질병획득완해,뇌척액EBV DNA재하하강.결론 뇌척액EBV DNA적검측대진단발생우CNS중EBV상관성질병십분중요,기재하수평가용우EBV상관성CNS질병적발생、발전급료효적평고.
Objective To explore the role of cerebrospinal fluid (CSF) EBV DNA loads in EBV-associated central nervous system (CNS) diseases after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods Forty six patients who had EBV-associated diseases or unexplainable CNS manifestations from 272 patients undergoing allo-HSCT were enrolled in this prospective study.Moreover,10 patients with EBV DNA-emia but without EBV-associated diseases and 5 patients who were negative for blood EBV DNA volunteered to have their CSF monitored as controls (platelet＞50 × 109/L).The EBV DNA loads of blood and CSF were monitored regularly by quantitative real-time polymerase chain reaction.Results Fourteen patients were diagnosed as EBV associated CNS diseases,including post-transplant lymphoproliferative disorder (PTLD) in t0 cases and encephalitis/myelitis in 4 cases.Except one patient with isolated CNS-PTLD,the EBV-DNA of blood was positive in all patients with EBV associated CNS diseases.The EBV DNA loads of CSF were significantly higher than those of blood (P =0.027).The levels of blood and CSF EBV DNA were declined with control of diseases in 5 patients who were responsive to the initial treatments.However,the levels of CSF EBV DNA were increased,and those of blood EBV DNA increased or remained unchanged with the development of the disease in the 9 patients who were unresponsive to the initial treatments.In addition,we observed 2 patients that their blood EBV DNA levels were decreased and lymphadenectasis became smaller,but CNS manifestations deteriorated,and the levels of CSF EBV DNA increased after intravenous rituximab-based treatment.Their CSF EBV DNA levels were decreased and neurological symptoms alleviated after treatment with intrathecal rituximab.Conclusion EBV DNA detection in CSF might be more specific and sensitive than that in blood for diagnosis,development and therapeutic evaluation of EBV-associated CNS diseases.