Viral encephalitis after haplo‐identical hematopoietic stem cell transplantation: Causative viral spectrum, characteristics, and risk factors

Zhang, Xiao-Hui; Zhang, Jiamin; Wang, Han; Chen, Huan; Chen, Yuhong; Wang, Feng-Rong; Wang, Jing‐Zhi; Zhang, Yuanyuan; Mo, Xiao‐Dong; Chen, Yao; Wang, Yu; Chang, Ying‐Jun; Xu, Lei; Liu, Kai-Yan; Huang, Xiao‐Jun

doi:10.1111/ejh.12855

Cited by 24 publications

(11 citation statements)

References 48 publications

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“…The incidence of various infections varied greatly after allo-HSCT. The pathogens of post-transplantation infections also varied among different reports ( Maschke et al, 1999 ; Roemer et al, 2001 ; Kang et al, 2015 ; Young et al, 2017 ; Zhang et al, 2017 ; Ford et al, 2020 ). These discrepancies are partly due to a variety of testing methods.…”

Section: Introductionmentioning

confidence: 99%

Metagenomic Next-Generation Sequencing vs. Traditional Pathogen Detection in the Diagnosis of Infection After Allogeneic Hematopoietic Stem Cell Transplantation in Children

Ding

et al. 2022

Front. Microbiol.

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Infection is a severe complication of allo-HSCT in children, however, the accurate detection of the infection is hard. In this study, we traced the records of 101 pediatric recipients with allo-HSCT to investigate the pathogens of infection, and collected 54 bronchoalveolar lavage fluid, 32 blood, and 15 cerebrospinal fluid samples. In these samples, 87 was with post-transplant infection and 14 without infection. Using the metagenomic next-generation sequencing (mNGS) and traditional pathogen detection, we compared their sensitivity and specificity to detect pathogens of infection. Our results showed that mNGS was more sensitive (89.7%) than conventional pathogen detection (21.8%), with a difference of 67.9% (P < 0.001), However, mNGS was less specific (78.5%) than traditional methods (92.9%), with a difference of 14.4% (P = 0.596). The sensitivity of mNGS for diagnosing pulmonary infections, bloodstream infections or viremia, and CNS infections post-transplant were 91.7, 85.7, and 90.9%, respectively. In contrast, the sensitivity of conventional testing for diagnosing pulmonary infections, bloodstream infections or viremia, and CNS infections post-transplant were 22.9, 21.4, and 18.2%, respectively. There were significant differences in the sensitivity of mNGS and conventional testing in BALF, blood, and CSF samples, with P values of 0.000, 0.000, and 0.002 respectively. Among the patients with pulmonary infection, 11 pathogens were both identified by mNGS and conventional testing, and 33 by mNGS only. The percentage with the mNGS-positive result was 44/48 (91.7%), including viruses (n = 12), bacteria (n = 17), fungi (n = 9) and mixed infections (n = 6). Among the patients diagnosed with fungal pneumonia (n = 9), the most prevalent pathogenic fungi were Pneumocystis jiroveci (n = 6), which were also detected in 4 patients with mixed infectious pneumonia. In the 28 blood specimens of patients with bloodstream infections or viremia, five patients were positive by both mNGS and conventional testing, 19 were positive by mNGS, and 1 was positive by traditional testing only. The percentage with the mNGS-positive results was 24/28 (85.7%), including viruses (n = 12), bacteria (n = 4), fungi (n = 3), and mixed infections (n = 5). Of the 15 CSF specimens enrolled, 11 patients were eventually diagnosed with CNS infections. Ten pathogens were identified by mNGS in the 11 patients, including viruses (n = 8), bacteria (n = 1), and fungi (n = 1). These results suggest that mNGS is more sensitive than conventional pathogen detection for diagnosing infections post HSCT in children which may help the clinic diagnosis. Pneumocystis jiroveci was the most frequent pathogen of pulmonary infections post-transplant, while viruses were the most common pathogens of CNS infections in allo-HSCT recipients.

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Section: Introductionmentioning

confidence: 99%

Metagenomic Next-Generation Sequencing vs. Traditional Pathogen Detection in the Diagnosis of Infection After Allogeneic Hematopoietic Stem Cell Transplantation in Children

Ding

et al. 2022

Front. Microbiol.

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“…All CSF samples were analyzed for varicella‐zoster virus (VZV), Epstein–Barr virus (EBV), cytomegalovirus (CMV), human herpes virus 6 (HHV‐6), herpes simplex virus (HSV), respiratory syncytial virus‐B (RSV‐B), respiratory syncytial virus‐A (RSV‐B), coxsackievirus group B type 3 (CVB‐3), BK virus (BKV), JC virus (JCV), Japanese encephalitis virus, and enteroviral encephalitis virus. Real‐time quantitative PCR was used to detect EBV‐ and CMV‐DNA, and qualitative PCR was used for other viruses as previously reported 42 . None of the IIDD patients included in our analysis had viral infection in the CNS.…”

Section: Methodsmentioning

confidence: 99%

Clinical risk factors and prognostic model for idiopathic inflammatory demyelinating diseases after haploidentical hematopoietic stem cell transplantation in patients with hematological malignancies

Deng

et al. 2021

American J Hematol

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Idiopathic inflammatory demyelinating diseases (IIDDs) of the central nervous system (CNS) are rare but serious neurological complications of haploidentical hematopoietic stem cell transplantation (haplo‐HSCT). However, the risk factors and a method to predict the prognosis of post‐transplantation CNS IIDDs are not available. This retrospective study first reviewed data from 4532 patients who received haplo‐HSCT during 2008–2019 in our center, and 184 patients (4.1%) with IIDDs after haplo‐HSCT were identified. Grades II to IV acute graft‐versus‐host disease (aGVHD) (p < 0.001) and chronic GVHD (cGVHD) (p = 0.009) were identified as risk factors for developing IIDDs after haplo‐HSCT. We then divided the 184 IIDD patients into a derivation cohort and validation cohort due to transplantation time to develop and validate a model for predicting the prognosis of IIDDs. In the multivariate analysis of the derivation cohort, four candidate predictors were entered into the final prognostic model: cytomegalovirus (CMV) infection, Epstein–Barr virus (EBV) infection, IgG synthesis (IgG‐syn) and spinal cord lesions. The prognostic model had an area under the receiver operating characteristic curve of 0.864 (95% CI: 0.803–0.925) in the internal validation cohort and 0.871 (95% CI: 0.806–0.931) in the external validation cohort. The calibration plots showed a high agreement between the predicted and observed outcomes. Decision curve analysis indicated that IIDD patients could benefit from the clinical application of the prognostic model. The identification of IIDD patients after allo‐HSCT who have a poor prognosis might allow timely treatment and improve patient survival and outcomes.

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“…In humans, CVB3 induces mild self-limiting illness with flu-like symptoms in adults [7]. However, under certain circumstances individuals can develop myocarditis [8,9], pancreatitis [10] and aseptic meningoencephalitis [11].…”

Section: Introductionmentioning

confidence: 99%

Application Route and Immune Status of the Host Determine Safety and Oncolytic Activity of Oncolytic Coxsackievirus B3 Variant PD-H

Hazini

Dieringer

Klingel³

et al. 2021

Viruses

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The coxsackievirus B3 strain PD-0 has been proposed as a new oncolytic virus for the treatment of colorectal carcinoma. Here, we generated a cDNA clone of PD-0 and analyzed the virus PD-H, newly generated from this cDNA, in xenografted and syngenic models of colorectal cancer. Replication and cytotoxic assays revealed that PD-H replicated and lysed colorectal carcinoma cell lines in vitro as well as PD-0. Intratumoral injection of PD-H into subcutaneous DLD-1 tumors in nude mice resulted in strong inhibition of tumor growth and significantly prolonged the survival of the animals, but virus-induced systemic infection was observed in one of the six animals. In a syngenic mouse model of subcutaneously growing Colon-26 tumors, intratumoral administration of PD-H led to a significant reduction of tumor growth, the prolongation of animal survival, the prevention of tumor-induced cachexia, and the elevation of CD3+ and dendritic cells in the tumor microenvironment. No virus-induced side effects were observed. After intraperitoneal application, PD-H induced weak pancreatitis and myocarditis in immunocompetent mice. By equipping the virus with target sites of miR-375, which is specifically expressed in the pancreas, organ infections were prevented. Moreover, employment of this virus in a syngenic mouse model of CT-26 peritoneal carcinomatosis resulted in a significant reduction in tumor growth and an increase in animal survival. The results demonstrate that the immune status of the host, the route of virus application, and the engineering of the virus with target sites of suitable microRNAs are crucial for the use of PD-H as an oncolytic virus.

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Viral encephalitis after haplo‐identical hematopoietic stem cell transplantation: Causative viral spectrum, characteristics, and risk factors

Abstract: Characteristics, such as onset time, response to treatment, and outcome, varied based on the different causative viruses.

Cited by 24 publications

References 48 publications

Metagenomic Next-Generation Sequencing vs. Traditional Pathogen Detection in the Diagnosis of Infection After Allogeneic Hematopoietic Stem Cell Transplantation in Children

Metagenomic Next-Generation Sequencing vs. Traditional Pathogen Detection in the Diagnosis of Infection After Allogeneic Hematopoietic Stem Cell Transplantation in Children

Clinical risk factors and prognostic model for idiopathic inflammatory demyelinating diseases after haploidentical hematopoietic stem cell transplantation in patients with hematological malignancies

Application Route and Immune Status of the Host Determine Safety and Oncolytic Activity of Oncolytic Coxsackievirus B3 Variant PD-H

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