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巨细胞病毒感染及儿童异基因造血干细胞移植受者耐药突变的影响:来自中国一家三级医院的回顾性研究

Cytomegalovirus Infection and the Implications of Drug-Resistant Mutations in Pediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients: A Retrospective Study from a Tertiary Hospital in China.

作者信息

Yu Uet, Wang Xiaodong, Zhang Xiaoling, Wang Chunjing, Yang Chunlan, Zhou Xiaohui, Li Yue, Huang Xiaochan, Wen Jing, Wen Feiqiu, Liu Sixi

机构信息

Department of Hematology and Oncology, Shenzhen Children's Hospital, Yitian Road No. 7019, Futian, Shenzhen, 518038, China.

出版信息

Infect Dis Ther. 2021 Sep;10(3):1309-1322. doi: 10.1007/s40121-021-00452-4. Epub 2021 May 8.

Abstract

INTRODUCTION

Drug-resistant cytomegalovirus (CMV) infection remains a challenge in the management of pediatric recipients of hematopoietic stem cell transplantation (HSCT). In this study, we retrospectively reviewed the clinical data on pediatric recipients of HSCT and identified known and unknown drug-resistant CMV variants.

METHODS

A total of 221 children underwent allogeneic HSCT between October 2017 and November 2019 at Shenzhen Children's Hospital; of these, 35 patients were suspected of having drug-resistant CMV infections and were tested for drug-resistant mutations in the UL97 and UL54 genes by Sanger sequencing.

RESULTS

Mutations in UL97 or UL54, or in both, were detected in 11 patients. Most of these mutations have not been previously reported. The UL97 mutation (A582V) was detected in only one patient who also harbored two UL54 mutations (T760X and R876W). One patient with both the G604S and T691A mutations in the UL54 gene died of CMV pneumonia. We investigated the risk factors associated with the development of drug-resistant CMV infection. Patients in whom both the donor and recipient had positive CMV serostatuses were less likely to have drug-resistant mutations (Fisher's exact test, p < 0.05).

CONCLUSION

Newly and previously detected CMV mutations in UL97 and UL54 may be associated with the development of drug-resistant CMV infection. The detection of these mutations may provide guidance for the management of post-transplant CMV infections.

摘要

引言

耐药巨细胞病毒(CMV)感染仍是造血干细胞移植(HSCT)儿科受者管理中的一项挑战。在本研究中,我们回顾性分析了HSCT儿科受者的临床数据,并鉴定出已知和未知的耐药CMV变异体。

方法

2017年10月至2019年11月期间,共有221名儿童在深圳儿童医院接受了异基因HSCT;其中,35例患者疑似发生耐药CMV感染,并通过Sanger测序检测了UL97和UL54基因中的耐药突变。

结果

在11例患者中检测到UL97或UL54或两者的突变。这些突变大多数以前未被报道。仅在一名患者中检测到UL97突变(A582V),该患者还携带两个UL54突变(T760X和R876W)。一名UL54基因同时存在G604S和T691A突变的患者死于CMV肺炎。我们调查了与耐药CMV感染发生相关的危险因素。供体和受体CMV血清学状态均为阳性的患者发生耐药突变的可能性较小(Fisher精确检验,p<0.05)。

结论

新检测到的以及先前检测到的UL97和UL54中的CMV突变可能与耐药CMV感染的发生有关。这些突变的检测可为移植后CMV感染的管理提供指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb77/8322184/4f1ed8046df5/40121_2021_452_Fig1_HTML.jpg

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