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多源化巨细胞病毒DNA定量检测在异基因造血干细胞移植后巨细胞病毒肺炎诊断中的应用

程昊钰 杨帆 杨怡欣 张书芹 张永平 张维婕 费新红 殷宇明 顾江英 王静波

程昊钰, 杨帆, 杨怡欣, 等. 多源化巨细胞病毒DNA定量检测在异基因造血干细胞移植后巨细胞病毒肺炎诊断中的应用[J]. 器官移植, 2021, 12(1): 96-102. doi: 10.3969/j.issn.1674-7445.2021.01.015
引用本文: 程昊钰, 杨帆, 杨怡欣, 等. 多源化巨细胞病毒DNA定量检测在异基因造血干细胞移植后巨细胞病毒肺炎诊断中的应用[J]. 器官移植, 2021, 12(1): 96-102. doi: 10.3969/j.issn.1674-7445.2021.01.015
Cheng Haoyu, Yang Fan, Yang Yixin, et al. Application of quantitative detection of multiple-source cytomegalovirus DNA in diagnosis of cytomegalovirus pneumonia after allogeneic hematopoietic stem cell transplantation[J]. ORGAN TRANSPLANTATION, 2021, 12(1): 96-102. doi: 10.3969/j.issn.1674-7445.2021.01.015
Citation: Cheng Haoyu, Yang Fan, Yang Yixin, et al. Application of quantitative detection of multiple-source cytomegalovirus DNA in diagnosis of cytomegalovirus pneumonia after allogeneic hematopoietic stem cell transplantation[J]. ORGAN TRANSPLANTATION, 2021, 12(1): 96-102. doi: 10.3969/j.issn.1674-7445.2021.01.015

多源化巨细胞病毒DNA定量检测在异基因造血干细胞移植后巨细胞病毒肺炎诊断中的应用

doi: 10.3969/j.issn.1674-7445.2021.01.015
基金项目: 

首都临床特色应用研究与成果推广 Z171100001017103

详细信息
    作者简介:

    程昊钰,女,1978年生,硕士,主治医师,研究方向为造血干细胞移植及其合并症的诊治,Email:chyky6778@hotmail.com

    通讯作者:

    王静波,女,1966年生,博士,主任医师,研究方向为造血干细胞移植治疗血液系统疾病,Email:dpwangjingbo@vip.sina.com

  • 中图分类号: R617, R373

Application of quantitative detection of multiple-source cytomegalovirus DNA in diagnosis of cytomegalovirus pneumonia after allogeneic hematopoietic stem cell transplantation

More Information
  • 摘要:   目的  研究不同来源[血浆、痰液、支气管肺泡灌洗液(BALF)]标本的巨细胞病毒(CMV)DNA定量检测对异基因造血干细胞移植后CMV肺炎的诊断价值。  方法  回顾性分析接受异基因造血干细胞移植的405例受者的临床资料,其中诊断为CMV肺炎的19例受者设为CMV肺炎组,选择同期仅发生CMV血症的229例受者、接受纤维支气管镜镜检的11例非CMV肺炎受者及根据病原学证据确诊细菌或真菌性肺炎进行痰培养的16例受者,分别设为对照A、B、C组。总结CMV肺炎的发生情况;分析CMV肺炎受者不同来源(血浆、痰液、BALF)标本的CMV DNA载量;总结CMV肺炎受者的预后情况。  结果  405例异基因造血干细胞移植受者中有19例发生了CMV肺炎,CMV肺炎总体发生率为4.7%(19/405)。CMV肺炎受者的血浆、痰液、BALF的CMV DNA载量均分别高于对照A、B、C组(均为P < 0.05)。19例受者中,有12例经抗病毒治疗后治愈,7例治疗失败死亡(其中3例放弃治疗),病死率为37%(7/19)。  结论  血浆、痰液、BALF的CMV DNA定量检测可提高CMV肺炎的诊断率,从而改善异基因造血干细胞移植受者的预后。

     

  • 表  1  CMV肺炎受者的治疗及预后情况

    Table  1.   Treatment and prognosis of recipients with CMV pneumonia

    例序 性别 一线抗病毒治疗 二线/三线抗病毒治疗 辅助抗病毒治疗 ALG / ATG 预后
    1 膦甲酸钠 人免疫球蛋白 ALG 治愈
    2 膦甲酸钠+半量更昔洛韦 CMV-IVIG 人免疫球蛋白 ALG 治愈
    3 更昔洛韦 人免疫球蛋白 ALG 治愈
    4 膦甲酸钠+半量更昔洛韦 CMV-IVIG 人免疫球蛋白 ALG 治愈
    5 膦甲酸钠 CMV-IVIG+CMV-CTL 人免疫球蛋白 ALG 治愈
    6 阿昔洛韦 CMV-IVIG+CMV-CTL 人免疫球蛋白 ATG 治愈
    7 更昔洛韦+半量膦甲酸钠 CMV-IVIG+CMV-CTL ALG 治愈
    8 膦甲酸钠 西多福韦+CMV-IVIG ALG 死亡
    9 更昔洛韦+半量膦甲酸钠 CMV-IVIG+CMV-CTL ALG 治愈
    10 更昔洛韦+半量膦甲酸钠 CMV-IVIG ALG 放弃
    11 更昔洛韦 CMV-IVIG 人免疫球蛋白 ALG 死亡
    12 更昔洛韦或膦甲酸钠 CMV-CTL ALG 治愈
    13 更昔洛韦+半量膦甲酸钠 CMV-IVIG ATG 放弃
    14 更昔洛韦或膦甲酸钠 CMV-IVIG+CMV-CTL 人免疫球蛋白 ALG 治愈
    15 膦甲酸钠+半量更昔洛韦 CMV-IVIG+CMV-CTL ALG 治愈
    16 膦甲酸钠+半量更昔洛韦 CMV-IVIG+CMV-CTL 人免疫球蛋白 ALG 放弃
    17 膦甲酸钠+更昔洛韦 CMV-IVIG ALG 治愈
    18 膦甲酸钠+更昔洛韦 CMV-IVIG 人免疫球蛋白 ALG 死亡
    19 更昔洛韦或膦甲酸钠 CMV-IVIG 人免疫球蛋白 ALG 死亡
    下载: 导出CSV
  • [1] ACOSTA E, BOWLIN T, BROOKS J, et al. Advances in the development of therapeutics for cytomegalovirus infections[J].J Infect Dis, 2020, 221(S1):S32-S44. DOI: 10.1093/infdis/jiz493.
    [2] 薛慧, 冯术青, 胡永超, 等.异基因造血干细胞移植后巨细胞病毒感染的分层治疗[J].中国组织工程研究, 2019, 23(5):756-760. DOI:10.3969/j.issn.2095-4344. 1561.

    XUE H, FENG SQ, HU YC, et al. Stratification therapy for cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation[J]. Chin J Tissue Eng Res, 2019, 23(5):756-760. DOI: 10.3969/j.issn.2095-4344.1561.
    [3] 李秋钰, 路明, 姚婉贞.造血干细胞移植患者巨细胞病毒肺炎的诊治进展[J].中华结核和呼吸杂志, 2019, 42(2):134-137.DOI:10.3760/cma.j.issn.1001-0939. 2019.02.012.

    LI QY, LU M, YAO WZ. Progress in diagnosis and treatment of cytomegalovirus pneumonia in patients with hematopoietic stem cell transplantation[J]. Chin J Tuberc Resp Dis, 2019, 42(2):134-137. DOI: 10.3760/cma.j.issn.1001-0939.2019.02.012.
    [4] 美国西雅图Fred Hutchinson癌症研究中心医学联合体.造血干细胞移植标准实践手册[M].俞立权, 译.北京: 人民卫生出版社, 2007.
    [5] 中华医学会器官移植学分会.器官移植受者巨细胞病毒感染临床诊疗规范(2019版)[J].器官移植, 2019, 10(2): 142-148. DOI: 10.3969/j.issn.1674-7445.2019.02.005.

    Branch of Organ Transplantation of Chinese Medical Association. Diagnosis and treatment specification for cytomegalovirus infection on recipients with organ transplantation in China (2019 edition)[J]. Organ Transplant, 2019, 10(2):142-148. DOI: 10.3969/j.issn.1674-7445.2019.02.005.
    [6] ISON MG, FISHMAN JA. Cytomegalovirus pneumonia in transplant recipients[J]. Clin Chest Med, 2005, 26(4):691-viii. DOI: 10.1016/j.ccm.2005.06.013.
    [7] LILLERI D, GERNA G, FURIONE M, et al. Use of a DNAemia cut-off for monitoring human cytomegalovirus infection reduces the number of preemptively treated children and young adults receiving hematopoietic stem-cell transplantation compared with qualitative pp65 antigenemia[J]. Blood, 2007, 110(7):2757-2760. DOI: 10.1182/blood-2007-03-080820.
    [8] VERGARA A, CILLONIZ C, LUQUE N, et al. Detection of human cytomegalovirus in bronchoalveolar lavage of intensive care unit patients[J].Eur Respir J, 2018, 51(2):1701332. DOI: 10.1183/13993003.01332-2017.
    [9] BOECKH M, STEVENS-AYERS T, TRAVI G, et al. Cytomegalovirus (CMV) DNA quantitation in bronchoalveolar lavage fluid from hematopoietic stem cell transplant recipients with CMV pneumonia[J]. J Infect Dis, 2017, 215(10):1514-1522. DOI: 10.1093/infdis/jix048.
    [10] ABDELAZIM IA, NUSAIR B, SVETLANA S, et al. Treatment of iron deficiency and iron deficiency anemia with intravenous ferric carboxymaltose in pregnancy[J]. Arch Gynecol Obstet, 2018, 298(6):1231-1232. DOI:10. 1007/s00404-018-4943-x.
    [11] LI Q, WANG K, GUO W, et al. Cytomegalovirus pneumonia in a patient with T-lymphoblastic leukemia/lymphoma after allogeneic hematopoietic stem cell transplantation: a case report[J]. Medicine (Baltimore), 2019, 98(4):e14221. DOI:10.1097/MD. 0000000000014221.
    [12] 程敏, 洪楠.造血干细胞移植后巨细胞病毒肺炎的高分辨CT特征与预后的相关性[J].中国医学影像学杂志, 2018, 26(9): 664-668. DOI:10.3969/j.issn.1005-5185. 2018.09.006.

    CHENG M, HONG N. Correlations between high-resolution CT features and prognosis of cytomegalovirus pneumonia after hematopoietic stem cell transplantation[J]. Chin J Med Imaging, 2018, 26(9):664-668. DOI: 10.3969/j.issn.1005-5185.2018.09.006.
    [13] 李乐, 王昱, 闫晨华, 等.异基因造血干细胞移植后低载量巨细胞病毒血症抢先治疗时机的临床研究[J].中华内科杂志, 2018, 57(3):191-195. DOI: 10.3760/cma.j.issn. 0578-1426.2018.03.008.

    LI L, WANG Y, YAN CH, et al. Clinical study of low cytomegalovirus viral load thresholds for preemptive antiviral therapy after allogeneic hematopoietic stem cell transplantion[J]. Chin J Intern Med, 2018, 57(3):191-195. DOI: 10.3760/cma.j.issn.0578-1426.2018.03.008.
    [14] CHEN K, CHENG MP, HAMMOND SP, et al. Antiviral prophylaxis for cytomegalovirus infection in allogeneic hematopoietic cell transplantation[J]. Blood Adv, 2018, 2(16):2159-2175. DOI: 10.1182/bloodadvances.2018016493.
    [15] LILLERI D, GERNA G. Strategies to control human cytomegalovirus infection in adult hematopoietic stem cell transplant recipients[J]. Immunotherapy, 2016, 8(9):1135-1149. DOI: 10.2217/imt-2015-0028.
    [16] HELIÖVAARA E, HUSAIN S, MARTINU T, et al. Drug-resistant cytomegalovirus infection after lung transplantation: incidence, characteristics, and clinical outcomes[J]. J Heart Lung Transplant, 2019, 38(12):1268-1274. DOI: 10.1016/j.healun.2019.09.005.
    [17] FRANGE P, LERUEZ-VILLE M. Maribavir, brincidofovir and letermovir: efficacy and safety of new antiviral drugs for treating cytomegalovirus infections[J]. Med Mal Infect, 2018, 48(8):495-502. DOI: 10.1016/j.medmal.2018.03.006.
    [18] JUNG S, MICHEL M, STAMMINGER T, et al. Fast breakthrough of resistant cytomegalovirus during secondary letermovir prophylaxis in a hematopoietic stem cell transplant recipient[J]. BMC Infect Dis, 2019, 19(1):388. DOI: 10.1186/s12879-019-4016-1.
    [19] KNOLL BM, SEITER K, PHILLIPS A, et al. Breakthrough cytomegalovirus pneumonia in hematopoietic stem cell transplant recipient on letermovir prophylaxis[J]. Bone Marrow Transplant, 2019, 54(6):911-912. DOI: 10.1038/s41409-018-0389-9.
    [20] AVERY RK, ARAV-BOGER R, MARR KA, et al. Outcomes in transplant recipients treated with foscarnet for ganciclovir-resistant or refractory cytomegalovirus infection[J]. Transplantation, 2016, 100(10):e74-e80. DOI: 10.1097/TP.0000000000001418.
    [21] LOCATELLI F, BERTAINA A, BERTAINA V, et al. Cytomegalovirus in hematopoietic stem cell transplant recipients-management of infection[J]. Expert Rev Hematol, 2016, 9(11):1093-1105. DOI: 10.1080/17474086.2016.1242406.
    [22] KE P, BAO X, ZHOU J, et al. Donor CMV-specific cytotoxic T lymphocytes successfully treated drug-resistant cytomegalovirus encephalitis after allogeneic hematopoietic stem cell transplantation[J]. Hematology, 2020, 25(1):43-47. DOI: 10.1080/16078454.2019.1710945.
    [23] INGELS J, DE SMET S, HEYNS K, et al. Treatment of a patient with severe cytomegalovirus (CMV) infection after haploidentical stem cell transplantation with donor-derived CMV-specific T cells[J]. Acta Clin Belg, 2020:1-5. DOI: 10.1080/17843286.2020.1752446.
    [24] 曹伟杰, 万鼎铭, 李丽, 等.异基因造血干细胞移植后巨细胞病毒感染和抢先治疗临床研究[J].中国实验血液学杂志, 2016, 24(4):1143-1148. DOI:10.7534/j.issn. 1009-2137.2016.04.034.

    CAO WJ, WAN DM, LI L, et al. Clinical study of cytomegalovirus infection and preemptive therapy after allogenic hematopoietic stem cell transplantation[J]. J Exp Hematol, 2016, 24(4):1143-1148. DOI: 10.7534/j.issn.1009-2137.2016.04.034.
    [25] EL HELOU G, RAZONABLE RR. Letermovir for the prevention of cytomegalovirus infection and disease in transplant recipients: an evidence-based review[J]. Infect Drug Resist, 2019, 12:1481-1491. DOI: 10.2147/IDR.S180908.
    [26] CHO SY, LEE DG, KIM HJ. Cytomegalovirus infections after hematopoietic stem cell transplantation: current status and future immunotherapy[J]. Int J Mol Sci, 2019, 20(11):2666. DOI: 10.3390/ijms20112666.
    [27] DZIEDZIC M, SADOWSKA-KRAWCZENKO I, STYCZYNSKI J. Risk factors for cytomegalovirus infection after allogeneic hematopoietic cell transplantation in malignancies: proposal for classification[J]. Anticancer Res, 2017, 37(12):6551-6556. DOI: 10.21873/anticanres.12111.
    [28] BOECKH M. New insights into cytomegalovirus infection after allogeneic hematopoietic stem cell transplant[J]. Clin Adv Hematol Oncol, 2017, 15(7):515-517. http://europepmc.org/abstract/MED/28749913
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出版历程
  • 收稿日期:  2020-09-20
  • 网络出版日期:  2021-01-19
  • 刊出日期:  2021-01-19

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