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异基因造血干细胞移植后急性移植物抗宿主病与肺损伤的关系
引用本文:刘启发,罗晓丹,范志平,宁涓,徐丹,孙竞,张钰,徐兵,魏永强. 异基因造血干细胞移植后急性移植物抗宿主病与肺损伤的关系[J]. 中华医学杂志, 2009, 89(8). DOI: 10.3760/cma.j.issn.0376-2491.2009.08.013
作者姓名:刘启发  罗晓丹  范志平  宁涓  徐丹  孙竞  张钰  徐兵  魏永强
作者单位:南方医科大学南方医院血液科,广州,510515
基金项目:国家高技术研究发展计划(863计划),广东省自然科学基金 
摘    要:目的 分析研究异基因造血干细胞移植(allo-HSCT)后急性移植物抗宿主病(Agvhd)患者CT影像学特征和Agvhd诱导肺损伤的发病机制.方法 对47例Ⅱ~Ⅳ度Agvhd患者进行胸部CT检查及Agvhd发生时血清干扰素γ(IFN-γ)和肿瘤坏死因子α(TNF-α)测定,4例抗Agvhd治疗后肺损伤疗效不佳患者进行肺组织活检,生存期>6个月的患者定期肺功能和CT检查.结果 47例患者在Agvhd后3 d内CT显示20例异常,其中17例疑诊为Agvhd诱导肺损伤(5例弥漫性间质渗出、7例弥漫性间质和肺泡渗出、5例弥漫性间质和部分小叶肺泡渗出);此外,9例患者有双侧胸腔和心包积液,4例伴心肌肥厚.血清IFN-γ和TNF-a水平在有肺损伤和无肺损伤患者分别为:(6.9±1.8)μg/L、(400±102)μg/L和(6.3±1.2)μg/L、(428±83)μg/,L,两者比较差异无统计学意义(均P>0.05).肺组织病理显示组织结构破坏、上皮细胞损伤、间质纤维化和以T细胞或巨噬细胞为主的浸润.Agvhd治疗与肺损伤治疗有效率呈正相关(r=0.771,P=0.01).结论 肺是Agvhd作用的靶器官之一,T细胞、巨噬细胞和IFN-Γtnf-α与Agvhd造成肺损伤有关,Agvhd肺损伤可迁延为晚期非感染性肺损伤.

关 键 词:造血干细胞移植  移植物抗宿主病  肺损伤

Association between acute graft versus host disease and lung injury after allogenic hematopoietic stem cell transplantation
LIU Qi-fa,LUO Xiao-dan,FAN Zhi-ping,NING Juan,XU Dan,SUN Jing,ZHANG Yu,XU Bing,WEI Yong-qiang. Association between acute graft versus host disease and lung injury after allogenic hematopoietic stem cell transplantation[J]. Zhonghua yi xue za zhi, 2009, 89(8). DOI: 10.3760/cma.j.issn.0376-2491.2009.08.013
Authors:LIU Qi-fa  LUO Xiao-dan  FAN Zhi-ping  NING Juan  XU Dan  SUN Jing  ZHANG Yu  XU Bing  WEI Yong-qiang
Abstract:Objective To investigate the characteristics of chest hiigh-resolution computed tomography(HRCT)and pathogenesis of acute graft versus host disease(aGVHD)-induced lung injury after allogenic hematopoietic stem cell transplantation(allo-HSCT).Methods Chest HRCT was performed in 47 patients with aGVHD of grade Ⅱ-Ⅳ after allo-HSCT.Twenty-four of the patients underwent different treatment regimens against aGVHD.Before the treatment peripheral blood samples were collected to detect the serum interferon-γ(IFN-γ)and tumor necrosis factor-α(TNF-α).Transbronchial biopsy was performed in 4 patients that failed to recover completely after treatment.Pulmonary function was examined in the patients who survived more than 6 months in every 3 months.Resuits Twenty of tlle 47 patients showed abnormal images by chest HRCT and 17 of the 20 patients were suspected to be witll aGVHD-induced lung iniury.The HRCT images were characterized by diffused interstitial infiltrate in 5 cases.diflused intemtitial and alveolar infiltrate in 7 cases.and diffused interstitial and segmental lobar alveolar infiltrate in 5 cases.Nine cases had bilateral pleural effusion and hydropericardium,including 4 eases accompanied by myocardial hypertrophy.The levels of serum IFN-γ and TNF-α of the patients with lung injury were(6.9±1.8)μg/L and(400±102)μg/L respectively,both not significantly different from those of the patients without lung injury[(6.3±1.2)μg/L and(428±83)μg/L respectively,P=0.202,0.306].The histopathology of the lung tissue was characterized by disorganization,epithelial cell damage,interstitial fibroplasias,and interstitial T lymphocyte or macrophage infiltrate.The effective rate of treatment for aGVHD-induced lung iniury was positively correlated witll that for aGVHD(r=0.771,P=0.01).Eleven of the 24 patients who survived more than 6 months had abnormal pulmonary function.including 7 out of tlle 9 patients with aGVHD-induced lung injury and 4 out the 15 patients without aGVHD-induced lung injury.There was no significant difference in the incidence of abnormal pulmonary function between the patients with and without lung injury(P=0.033).Conclusions Lung is one of the target organs of aGVHD.IFN-γ and TNF-α may play a role in the pathogenesis of aGVHD-induced lung injury.Acute GVHD-induced lung injury may progress to late-onset non-infectiouslunginjury.
Keywords:Hematopoietic stem cell transplantation  Graft VS host disease  Lung injury
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