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BK 病毒感染在造血干细胞移植后儿童中的分析:一项回顾性单中心研究。

Analysis of BK Virus Infection in Children After Hematopoietic Cell Transplantation: A Retrospective Single-center Study.

机构信息

Beijing Key Laboratory of Pediatric Hematology Oncology.

National Key Discipline of Pediatrics.

出版信息

J Pediatr Hematol Oncol. 2024 Oct 1;46(7):e487-e492. doi: 10.1097/MPH.0000000000002922. Epub 2024 Jul 15.

DOI:10.1097/MPH.0000000000002922
PMID:39008534
Abstract

BACKGROUND

BK virus (BKV) is one of the most common causes of hemorrhagic cystitis (HC) in children undergoing hematopoietic stem cell transplantation (HSCT). Viruses can be found in urine and serum of immunocompromised patients.

OBJECTIVE

This study aimed to evaluate the incidence, clinical course, and risk factors for BKV infection in children undergoing HSCT.

METHODS

Retrospectively analyzed children who underwent HSCT at Beijing Children's Hospital, Capital Medical University from June 2020 to June 2022. Data related to the clinical manifestations, engraftment, and prognosis were extracted from medical records. Patients were divided into the case group and the control group, according to the BKV infection or not after HSCT.

RESULTS

A total of 149 patients were enrolled in this study, and 61 (40.9%) patients developed BKV infection after HSCT. Among the 61 patients, BKV load was detected in all patients in urine samples and 22 patients in blood samples. The median value of BKV DNA copies in urine and plasma were 9.50×10 7 (5.37×10 2 to 6.84×10 9 ) copies/mL and 2.97×10 3 (9.96×10 2 to 3.58×10 8 ) copies/mL, respectively. The median time from beginning of the conditioning regimen to BKV infection was 23 (0 to 273) days, and the first positive time of urinary BKV was earlier than that of blood (13.5 d [0.0 to 123.0 d] vs. 30.5 d [7.0 to 165.0 d], P =0.003). Among the patients with BKV infection, 36 (59.0%) patients met the diagnosis of hemorrhagic cystitis (HC), and the incidence was higher than that in the control group ( P <0.001). Similarly, 15 (24.6%) patients developed renal function damage in the case group and the proportion was higher than that in the control group. The median follow-up was 5.67 (0.03 to 24.90) months, and there was no significant difference in 1-year overall survival rate between the case group and the control group (84.2%±5.7% vs. 95.3%±2.3%, P =0.688), but the incidence of TA-TMA/VOD (31.1%) and diffuse alveolar hemorrhage (9.8%) in the case group was higher than that in the control group ( P =0.002 and 0.038, respectively). Multivariate analysis showed that age above 5 years old (OR=9.039, 95% CI: 3.561-24.333, P <0.001) and use of MMF (OR=2.708, 95% CI: 1.041-7.044, P <0.05) were independent risk factors for BKV infection after HSCT.

CONCLUSION

Among children after HSCT, the incidence of BKV infection was high and BKV infection was associated with an increased incidence of TA-TMA/VOD and diffuse alveolar hemorrhage. Patients older than 5 years of age at the time of HSCT and treated with MMF were more likely to develop BKV infection.

摘要

背景

BK 病毒(BKV)是儿童造血干细胞移植(HSCT)后发生出血性膀胱炎(HC)的最常见原因之一。病毒可存在于免疫功能低下患者的尿液和血清中。

目的

本研究旨在评估接受 HSCT 的儿童中 BKV 感染的发生率、临床过程和危险因素。

方法

回顾性分析 2020 年 6 月至 2022 年 6 月在北京儿童医院、首都医科大学附属接受 HSCT 的儿童。从病历中提取与临床表现、植入和预后相关的数据。根据 HSCT 后是否发生 BKV 感染,将患者分为病例组和对照组。

结果

本研究共纳入 149 例患者,其中 61 例(40.9%)在 HSCT 后发生 BKV 感染。在 61 例患者中,所有患者的尿液样本中均检测到 BKV 载量,22 例患者的血液样本中也检测到 BKV 载量。尿液和血浆中 BKV DNA 拷贝数的中位数分别为 9.50×10 7(5.37×10 2 至 6.84×10 9)拷贝/mL 和 2.97×10 3(9.96×10 2 至 3.58×10 8)拷贝/mL。从开始预处理到 BKV 感染的中位数时间为 23(0 至 273)天,尿液 BKV 的首次阳性时间早于血液(13.5 d [0.0 至 123.0 d] 与 30.5 d [7.0 至 165.0 d],P =0.003)。在 BKV 感染患者中,36(59.0%)例患者符合出血性膀胱炎(HC)的诊断,发生率高于对照组(P <0.001)。同样,病例组中有 15(24.6%)例患者发生肾功能损害,比例高于对照组。中位随访时间为 5.67(0.03 至 24.90)个月,病例组和对照组 1 年总生存率无显著差异(84.2%±5.7% vs. 95.3%±2.3%,P =0.688),但病例组 TA-TMA/VOD(31.1%)和弥漫性肺泡出血(9.8%)的发生率高于对照组(P =0.002 和 0.038,分别)。多因素分析显示,年龄大于 5 岁(OR=9.039,95%CI:3.561-24.333,P <0.001)和使用 MMF(OR=2.708,95%CI:1.041-7.044,P <0.05)是 HSCT 后 BKV 感染的独立危险因素。

结论

在接受 HSCT 的儿童中,BKV 感染的发生率较高,BKV 感染与 TA-TMA/VOD 和弥漫性肺泡出血的发生率增加有关。HSCT 时年龄大于 5 岁且接受 MMF 治疗的患者更易发生 BKV 感染。

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引用本文的文献

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Recent Insights into the Pathogenesis, Diagnostics, and Treatment of BK Virus Infections in Children After Hematopoietic Stem Cell Transplantation.造血干细胞移植后儿童BK病毒感染的发病机制、诊断与治疗的最新见解
Pathogens. 2025 Feb 28;14(3):236. doi: 10.3390/pathogens14030236.