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肝移植受者移植后淋巴组织增生性疾病的单中心诊疗经验

刘静怡 孙丽莹 朱志军 魏林 刘颖 曾志贵 曲伟 刘思琦

刘静怡, 孙丽莹, 朱志军, 等. 肝移植受者移植后淋巴组织增生性疾病的单中心诊疗经验[J]. 器官移植, 2020, 11(6): 711-718. doi: 10.3969/j.issn.1674-7445.2020.06.010
引用本文: 刘静怡, 孙丽莹, 朱志军, 等. 肝移植受者移植后淋巴组织增生性疾病的单中心诊疗经验[J]. 器官移植, 2020, 11(6): 711-718. doi: 10.3969/j.issn.1674-7445.2020.06.010
Liu Jingyi, Sun Liying, Zhu Zhijun, et al. Diagnosis and treatment of posttransplant lymphoproliferative diseases in liver transplant recipients: a single-center experience[J]. ORGAN TRANSPLANTATION, 2020, 11(6): 711-718. doi: 10.3969/j.issn.1674-7445.2020.06.010
Citation: Liu Jingyi, Sun Liying, Zhu Zhijun, et al. Diagnosis and treatment of posttransplant lymphoproliferative diseases in liver transplant recipients: a single-center experience[J]. ORGAN TRANSPLANTATION, 2020, 11(6): 711-718. doi: 10.3969/j.issn.1674-7445.2020.06.010

肝移植受者移植后淋巴组织增生性疾病的单中心诊疗经验

doi: 10.3969/j.issn.1674-7445.2020.06.010
基金项目: 

首都临床特色应用研究 Z181100001718220

详细信息
    作者简介:

    刘静怡,女,1994年生,硕士研究生,研究方向为肝移植后淋巴组织增生性疾病,Email:lljjyy19940407@126.com

    通讯作者:

    孙丽莹,女,1967年生,博士,主任医师,研究方向为肝移植及肝病患者的重症管理、移植感染与免疫,Email:sunxlx@outlook.com

  • 中图分类号: R617, R733.4

Diagnosis and treatment of posttransplant lymphoproliferative diseases in liver transplant recipients: a single-center experience

More Information
  • 摘要:   目的  总结肝移植受者移植后淋巴组织增生性疾病(PTLD)的发病情况和诊疗经验。  方法  回顾性分析734例肝移植受者的临床资料,收集肝移植受者中PTLD的发病情况、临床症状、实验室数据及影像学资料;分析PTLD受者的病理学结果与治疗方式;分析PTLD受者的预后情况。  结果  肝移植受者PTLD发生率为2.2%(16/734), 中位术后发病时间为8(3, 46)个月。PTLD的临床表现主要为发热、淋巴结肿大,部分出现贫血、肝脾肿大、肝功能异常和消化系统症状等。16例PTLD受者中,1例他克莫司血药浓度异常升高;6例转氨酶升高;14例爱泼斯坦-巴尔病毒(EBV)DNA载量升高;5例巨细胞病毒(CMV)DNA载量升高。13例受者正电子发射计算机体层显像仪(PET/CT)检查提示相关肿大淋巴结18F-氟代脱氧葡萄糖代谢增高;2例受者颈部及腹部CT检查提示相应区域多发淋巴结肿大;1例受者仅超声提示淋巴结肿大。16例PTLD受者均行病理学检查, 其中13例受者原位杂交结果提示EBV编码的小RNA(EBER)阳性。降低免疫抑制剂水平是PTLD受者的基础治疗方案,根据不同病理类型的PTLD可联合利妥昔单抗靶向治疗及化学药物治疗;针对肿大淋巴结,给予手术及放射治疗。1例受者因PTLD治疗致移植肝衰竭死亡。  结论  肝移植术后免疫抑制剂的使用可增加PTLD的患病风险,PTLD在儿童肝移植受者中发生率高于成人,尽早诊断和合理治疗可极大地改善PTLD受者的预后。

     

  • 图  1  例7受者的PET/CT影像学表现

    注:A、B、C图分别为例7受者2016年、2017年、2018年PET/CT图像。A图可见脾脏左侧及右前下腹膜增厚,18F-FDG代谢活跃,考虑PTLD;B图为例7受者治疗1年后复查PET/CT图像,可见原代谢增高灶较前体积减小,代谢降低,颈部淋巴结体积增大,18F-FDG代谢增高;C图示原代谢增高灶较前无明显变化,颈部淋巴结代谢较2017年降低,体积减小。

    Figure  1.  PET/CT imaging manifestation of case 7 recipient

    图  2  例7受者淋巴结活检的病理学表现

    注:A图为淋巴瘤组织病理学图片(苏木素-伊红,×200);B图为淋巴瘤组织CD20阳性图片(免疫组织化学,×200);C图为淋巴瘤组织EBER阳性图片(原位杂交,×200)

    Figure  2.  Pathological manifestation of lymph node biopsy in case 7 recipient

    表  1  16例肝移植术后PTLD受者的临床资料

    Table  1.   Clinical data of 16 cases of PTLD recipients after liver transplantation

    例序 性别 年龄 术后发病时间(月) 术前血清学状态 病理学结果 治疗 预后
    EBV CMV EBER原位杂交 组织学分型
    1 19个月 8 D+/R+ D+/R+ 阳性 PTLD,早期病变 RIS;利妥昔单抗靶向治疗2周期 部分缓解
    2 29个月 6 D-/R- D-/R- 阳性 PTLD,早期病变 RIS;利妥昔单抗靶向治疗2周期 部分缓解
    3 8个月 16 D- D- 阳性 颈部淋巴结:淋巴组织反应性增生伴EBV感染;肝脏穿刺组织:单形性,EBV阳性T细胞淋巴组织增生性疾病 RIS 疾病稳定
    4 6个月 9 R- D-/R- 阳性 多形性PTLD RIS;RIS后转氨酶升高,甲泼尼龙冲击治疗3 d;利妥昔单抗靶向治疗1周期 部分缓解
    5 27个月 46 - - 阴性 淋巴组织反应性增生 RIS 疾病稳定
    6 7个月 11 D-/R- D-/R- 阳性 PTLD,传染性单核细胞增生性早期病变 RIS;利妥昔单抗靶向治疗2周期 疾病稳定
    7 13个月 7 D+/R- D+/R+ 阳性 PTLD,单形性,非霍奇金弥漫大B细胞淋巴瘤 RIS;手术切除坏死肠管;R-CHOP方案化疗1周期 部分缓解
    8 9个月 7 D-/R- D-/R- 阴性 淋巴组织反应性增生伴慢性炎症 RIS;阿昔洛韦抗病毒治疗 疾病稳定
    9 6个月 9 D- D- 阳性 淋巴结非破坏性PTLD(传染性单核细胞增生性早期病变)伴皮病性淋巴结炎 RIS 疾病稳定
    10 5个月 10 R- D-/R- 阳性 淋巴结滤泡为主的反应性增生,伴EBV感染 RIS 疾病稳定
    11 13个月 5 - - 阳性 PTLD,早期病变;形态符合卡波西肉瘤 RIS;利妥昔单抗靶向治疗1周期 PTLD复发
    12 32个月 36 D- D- 阳性 淋巴组织反应性增生 RIS 疾病稳定
    13 8个月 4 D-/R- D-/R- 阳性 淋巴组织反应性增生 RIS 疾病稳定
    14 46岁 7 - - 阳性 多形性PTLD RIS;利妥昔单抗靶向治疗4周期;肝门部病灶放射治疗 疾病稳定
    15 46岁 11 D+ D- 阴性 PTLD,单形性,呈非霍奇金弥漫大B细胞淋巴瘤改变 RIS;R-COP化疗1周期,R-CHOP化疗2周期,利妥昔单抗靶向治疗1周期;病灶部位放射治疗 PTLD部分缓解,移植肝衰竭死亡
    16 53岁 3 - - 阳性 多形性PTLD RIS,后因排斥反应恢复用药;停吗替麦考酚酯;利妥昔单抗靶向治疗1周期,R-COP化疗1周期,VP16⑨联合CHOP⑩化疗1周期,后患者拒绝化疗 部分缓解
    注:①EBER为EBV编码的小RNA。
    ② D为供者。
    ③ R为受者。
    ④ RIS为降低免疫抑制剂水平,包括减量或停用他克莫司、伴或不伴有同时口服糖皮质激素。
    ⑤-为未检测。
    ⑥ R-CHOP为利妥昔单抗+环磷酰胺+多柔比星+长春新碱+地塞米松。
    ⑦化疗为化学药物治疗。
    ⑧ R-COP为利妥昔单抗+环磷酰胺+长春新碱+地塞米松。
    ⑨ VP16为依托泊苷。
    ⑩ CHOP为环磷酰胺+多柔比星+长春新碱+地塞米松。
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  • 收稿日期:  2020-08-04
  • 网络出版日期:  2021-01-19
  • 刊出日期:  2021-01-19

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