留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

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。
    下载: 导出CSV
  • [1] DIERICKX D, HABERMANN TM. Post-transplantation lymphoproliferative disorders in adults[J]. N Engl J Med, 2018, 378(6):549-562. DOI: 10.1056/NEJMra1702693.
    [2] SWERDLOW SH, CAMPO E, PILERI SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms[J]. Blood, 2016, 127(20):2375-2390. DOI: 10.1182/blood-2016-01-643569.
    [3] QIN T, GU XQ, JEONG SS, et al. Impact of EBV infection and immune function assay for lymphoproliferative disorder in pediatric patients after liver transplantation: a single-center experience[J]. Hepatobiliary Pancreat Dis Int, 2020, 19(1):3-11. DOI: 10.1016/j.hbpd.2019.12.005.
    [4] KEMPF C, TINGUELY M, RUSHING EJ. Posttransplant lymphoproliferative disorder of the central nervous system[J]. Pathobiology, 2013, 80(6):310-318. DOI:10. 1159/000347225.
    [5] SINGAVI AK, HARRINGTON AM, FENSKE TS. Posttransplant lymphoproliferative disorders[J]. Cancer Treat Res, 2015, 165:305-327. DOI:10.1007/978-3-319-13150- 4_13.
    [6] L'HUILLIER AG, DIPCHAND AI, NG VL, et al. Posttransplant lymphoproliferative disorder in pediatric patients: characteristics of disease in EBV-seropositive recipients[J]. Transplantation, 2019, 103(11):e369-e374. DOI: 10.1097/TP.0000000000002898.
    [7] HSU CT, CHANG MH, HO MC, et al. Post-transplantation lymphoproliferative disease in pediatric liver recipients in Taiwan[J]. J Formos Med Assoc, 2019, 118(11):1537- 1545. DOI: 10.1016/j.jfma.2018.12.023.
    [8] SEO E, KIM J, OH SH, et al. Epstein-Barr viral load monitoring for diagnosing post-transplant lymphoproliferative disorder in pediatric liver transplant recipients[J]. Pediatr Transplant, 2020, 24(4):e13666. DOI: 10.1111/petr.13666.
    [9] NARKEWICZ MR, GREEN M, DUNN S, et al. Decreasing incidence of symptomatic Epstein-Barr virus disease and posttransplant lymphoproliferative disorder in pediatric liver transplant recipients: report of the studies of pediatric liver transplantation experience[J]. Liver Transpl, 2013, 19(7):730-740. DOI: 10.1002/lt.23659.
    [10] ØSTENSEN AB, SANENGEN T, HOLTER E, et al. No effect of treatment with intravenous ganciclovir on Epstein-Barr virus viremia demonstrated after pediatric liver transplantation[J]. Pediatr Transplant, 2017, 21(6):e13010. DOI: 10.1111/petr.13010.
    [11] ALDABBAGH MA, GITMAN MR, KUMAR D, et al. The role of antiviral prophylaxis for the prevention of Epstein-Barr virus-associated posttransplant lymphoproliferative disease in solid organ transplant recipients: a systematic review[J]. Am J Transplant, 2017, 17(3):770-781. DOI: 10.1111/ajt.14020.
    [12] ALLEN UD, PREIKSAITIS JK, AST Infectious Diseases Community of Practice. Epstein-Barr virus and posttransplant lymphoproliferative disorder in solid organ transplantation[J]. Am J Transplant, 2013, 13 (Suppl 4): 107-120. DOI: 10.1111/ajt.12104.
    [13] SILVA JT, FERNÁNDEZ-RUIZ M, AGUADO JM. Prevention and therapy of viral infections in patients with solid organ transplantation[J]. Enferm Infecc Microbiol Clin, 2020, DOI: 10.1016/j.eimc.2020.01.021[Epub ahead of print].
    [14] GEORGE TI, JENG M, BERQUIST W, et al. EpsteinBarr virus-associated peripheral T-cell lymphoma and hemophagocytic syndrome arising after liver transplantation: case report and review of the literature[J]. Pediatr Blood Cancer, 2005, 44(3):270-276. DOI:10.1002/ pbc.20231.
    [15] MUMTAZ K, FAISAL N, MARQUEZ M, et al. Posttransplant lymphoproliferative disorder in liver recipients: characteristics, management, and outcome from a singlecentre experience with >1 000 liver transplantations[J]. Can J Gastroenterol Hepatol, 2015, 29(8):417-422. DOI: 10.1155/2015/517359.
    [16] BISHNOI R, MINISH J, FRANKE AJ, et al. Singleinstitution retrospective analysis of prognostic factors influencing very late-onset post-transplant lymphoproliferative disorder[J]. Cureus, 2020, 12(2):e6912.DOI: 10.7759/cureus.6912.
    [17] PETERS AC, AKINWUMI MS, CERVERA C, et al. The changing epidemiology of posttransplant lymphoproliferative disorder in adult solid organ transplant recipients over 30 years: a single-center experience[J]. Transplantation, 2018, 102(9):1553-1562. DOI:10.1097/ TP.0000000000002146.
    [18] ABSALON MJ, KHOURY RA, PHILLIPS CL. Posttransplant lymphoproliferative disorder after solid-organ transplant in children[J]. Semin Pediatr Surg, 2017, 26(4):257-266. DOI: 10.1053/j.sempedsurg.2017.07.002.
    [19] CAMACHO JC, MORENO CC, HARRI PA, et al. Posttransplantation lymphoproliferative disease: proposed imaging classification[J]. Radiographics, 2014, 34(7):2025- 2038. DOI: 10.1148/rg.347130130.
    [20] XU YF, YANG JG. Roles of F-18-fluoro-2-deoxy-glucose PET/computed tomography scans in the management of post-transplant lymphoproliferative disease in pediatric patient[J]. PET Clin, 2020, 15(3):309-319. DOI:10.1016/ j.cpet.2020.03.006.
    [21] EVENS AM, ROY R, STERRENBERG D, et al. Posttransplantation lymphoproliferative disorders: diagnosis, prognosis, and current approaches to therapy[J]. Curr Oncol Rep, 2010, 12(6):383-394. DOI:10.1007/s11912- 010-0132-1.
    [22] GROSS TG, ORJUELA MA, PERKINS SL, et al. Lowdose chemotherapy and rituximab for posttransplant lymphoproliferative disease (PTLD): a children's oncology group report[J]. Am J Transplant, 2012, 12(11):3069- 3075. DOI: 10.1111/j.1600-6143.2012.04206.x.
    [23] TRAPPE R, OERTEL S, LEBLOND V, et al. Sequential treatment with rituximab followed by CHOP chemotherapy in adult B-cell post-transplant lymphoproliferative disorder (PTLD): the prospective international multicentre phase 2 PTLD-1 trial[J]. Lancet Oncol, 2012, 13(2):196-206. DOI: 10.1016/S1470-2045(11)70300-X.
    [24] IGNACAK E, SUŁOWICZ J, GIZA A, et al. Posttransplant lymphoproliferative disorder in a patient after kidney transplant, 5-year follow-up: a case report[J]. Transplant Proc, 2020, 52(8):2517-2519. DOI:10.1016/ j.transproceed.2020.02.083.
    [25] VAN BESIEN K, BACHIER-RODRIGUEZ L, SATLIN M, et al. Prophylactic rituximab prevents EBV PTLD in haplo-cord transplant recipients at high risk[J]. Leuk Lymphoma, 2019, 60(7):1693-1696. DOI:10.1080/10428 194.2018.1543877.
    [26] ROSSIGNOL J, TERRIOU L, ROBU D, et al. Radioimmunotherapy ((90) y-ibritumomab tiuxetan) for posttransplant lymphoproliferative disorders after prior exposure to rituximab[J]. Am J Transplant, 2015, 15(7):1976-1981. DOI: 10.1111/ajt.13244.
    [27] CHIOU FK, BEATH SV, WILKIE GM, et al. Cytotoxic T-lymphocyte therapy for post-transplant lymphoproliferative disorder after solid organ transplantation in children[J]. Pediatr Transplant, 2018, 22(2). DOI: 10.1111/petr.13133.
    [28] BUNCHORNTAVAKUL C, REDDY KR. Epstein-Barr virus and cytomegalovirus infections of the liver[J]. Gastroenterol Clin North Am, 2020, 49(2):331-346. DOI: 10.1016/j.gtc.2020.01.008.
  • 加载中
图(2) / 表(1)
计量
  • 文章访问数:  463
  • HTML全文浏览量:  269
  • PDF下载量:  46
  • 被引次数: 0
出版历程
  • 收稿日期:  2020-08-04
  • 网络出版日期:  2021-01-19
  • 刊出日期:  2021-01-19

目录

    /

    返回文章
    返回