Dataset Information

Pulmonary cytomegalovirus (CMV) DNA shedding in allogeneic hematopoietic stem cell transplant recipients: Implications for the diagnosis of CMV pneumonia.

ABSTRACT:

Objectives

To date no definitive cut-off value for cytomegalovirus (CMV) DNA load in bronchoalveolar lavage (BAL) fluid specimens has been established to discriminate between CMV pneumonia and pulmonary CMV DNA shedding in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients.

Methods

The current retrospective study is aimed at assessing the range of CMV DNA loads quantified in BAL fluid specimens from allo-HSCT patients with pneumonia in which different microorganisms were causally involved.

Results

A total of 144 BAL specimens from 123 patients were included. CMV DNA was detected in 56 out of 144 BAL fluid specimens and the median CMV DNA load from patients in whom CMV pneumonia was unlikely or could be tentatively ruled out was 1210 (31-68, 920) IU/ml. The frequency of CMV DNA detection and median CMV DNA loads were comparable, irrespective of the attributable cause of pneumonia. Detection of CMV DNA loads in BAL fluid specimens >500 IU/ml was independently associated with pneumonia-attributable mortality.

Conclusions

The current study highlights the difficulty in establishing universal CMV DNA load thresholds in BAL fluid specimens for distinguishing between CMV pneumonia and pulmonary CMV DNA shedding, and suggests that the presence of CMV DNA in BAL fluid specimens beyond a certain level may have a deleterious impact on patient outcome.

SUBMITTER: Pinana JL

PROVIDER: S-EPMC7126576 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Pulmonary cytomegalovirus (CMV) DNA shedding in allogeneic hematopoietic stem cell transplant recipients: Implications for the diagnosis of CMV pneumonia.

Piñana José Luis JL Giménez Estela E Gómez María Dolores MD Pérez Ariadna A González Eva María EM Vinuesa Víctor V Hernández-Boluda Juan Carlos JC Montoro Juan J Salavert Miguel M Tormo Mar M Amat Paula P Moles Paula P Carretero Carlos C Balaguer-Roselló Aitana A Sanz Jaime J Sanz Guillermo G Solano Carlos C Navarro David D

The Journal of infection 20190221 5

<h4>Objectives</h4>To date no definitive cut-off value for cytomegalovirus (CMV) DNA load in bronchoalveolar lavage (BAL) fluid specimens has been established to discriminate between CMV pneumonia and pulmonary CMV DNA shedding in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients.<h4>Methods</h4>The current retrospective study is aimed at assessing the range of CMV DNA loads quantified in BAL fluid specimens from allo-HSCT patients with pneumonia in which different microorgani ...[more]

PMID: 30797790

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Project description:The dynamics of recovery of cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) and its impact on controlling clinically significant CMV infections following hematopoietic stem cell transplant (HSCT) are rarely reported in pediatric HSCT recipients. In this study, dynamics of recovery of CMV-specific CMI and its clinical significance in controlling CMV viremia and clinically significant CMV infections were assessed in pediatric allogeneic HSCT recipients. All subjects underwent CMV pp65- and IE1-specific enzyme-linked immune absorbent spot (ELISPOT) assays just before transplantation and then monthly until the detection of CMV-specific CMI with ? 5 spot-forming cells (SFC) / 2.0 × 105 cells. Clinically significant CMV infections were defined as CMV diseases, prolonged CMV infections, recurrent CMV infections or late onset CMV infections. Among 52 recipients, 88.5% of recipients recovered CMV-specific CMI with ? 5 SFC/ 2.0 × 105 cells at a median of 34 days (interquartile range [IQR]: 29-95 days) following HSCT, 55.8% at 30 days following HSCT, and 73.1% at 90 days following HSCT. The presence of CMV-specific CMI before HSCT was the significant factors for the reconstitution of CMV specific CMI after HSCT (adjusted odds ratio [aOR] = 13.33; 95% confidence interval [CI] = 1.21-142.86). After HSCT, 30 recipients experienced CMV viremia, of which 20 were clinically significant CMV infections. The full recovery of CMV-specific CMI with ? 50 SFC / 2.0 × 105 cells after HSCT was the protective factor for the development of clinically significant CMV infections (aOR = 0.13; 95% CI = 0.22-0.71). In the haploidentical HSCT recipients, 82.1% recovered CMV-specific CMI at a median of 65 days after HSCT (IQR: 34-118 days) with a tendency to recover their CMV-specific CMI later than did those from non-haploidentical donors (65 days vs. 30 days; P = 0.001). Clinically significant CMV infections tended to occur more frequently in the haploidentical HSCT recipients compared to those with matched donor HSCT (46.4% vs. 29.2%; P = 0.205). The full recovery of CMV-specific CMI with ? 50 SFC/2.0 × 105 cells after HSCT also lowered the risk of development of clinically significant CMV infections (aOR = 0.08; 95% CI = 0.01-0.90). However, transplantation from haploidentical donors was a significant risk factor hampering recovery of CMV-specific CMI (aOR = 0.08; 95% CI = 0.01-0.86) and full recovery of CMV-specific CMI (aOR = 0.05; 95% CI = 0.01-0.50). Pre-transplant CMV-specific CMI influenced the recovery of CMV-specific CMI, and the full recovery of CMV-specific CMI could be a surrogate marker for preventing clinically significant CMV infections in pediatric HSCT recipients. Immunologic monitoring using ELISPOT assay before and after HSCT helps in identifying patients with a high risk of CMV infection and in controlling CMV infection.

Project description:BACKGROUND: Based on sequence variation in the UL55 gene that encodes glycoprotein B (gB), human cytomegalovirus (CMV) can be classified into four gB genotypes. Previous studies have suggested an association between CMV gB genotype and clinical outcome in patients who underwent an allogeneic hematopoietic stem cell transplant (HSCT). The goals of this study were identify patients with active infection caused by CMV in recipients of HSCT; determine the prevalence of CMV genotypes in the study group; correlate genotype with CMV disease, acute GVHD and overall survival. METHODS: The diagnosis of active CMV infection after allogeneic HSCT was detected by antigenemia (AGM) and/or nested-PCR (N-PCR). Positive samples from patients with active CMV infection were submitted to genotyping using N-PCR to amplify a region of UL55, followed by restriction analysis based on HinfI and RsaI digestion. Real-time PCR (qPCR) was used to determine the viral load during active CMV infection and antiviral treatment. RESULTS: Sixty-three allogeneic HSCT recipients were prospectively evaluated; 49/63 (78%) patients were infected with CMV genotypes - gB1 19/49 (39%), gB2 17/49 (35%), gB3 3/49 (6%), gB4 7/49 (14%) - and 3 (6%) had mixed CMV genotypes (gB1 + gB3, gB1 + gB4 and gB2 + gB4). Characterized by gastrointestinal disease, CMV disease occurred in 3/49 (6.1%) patients, who had CMV gB3 genotype. These gB3 genotype patients presented an increasing AGM number, mean 125 (± 250) (P = 0.70), and qPCR copies/ml, mean 37938 (SD ± 50542) (P = 0.03), during antiviral treatment, when compared with other CMV genotypes. According to CMV genotypes, stratified overall survival was 55% for gB1, 43% for gB2; 0% for gB3 and 57% for gB4 (P = 0.03). CONCLUSIONS: One of the restrictions of the presented study was the low number of CMV gB sub-cohorts). However, we demonstrated that the frequency of active CMV infection in this HSCT population was high, and the most prevalent genotype in these patients with active CMV infection was gB1 and gB2 genotype (74%). In Brazil, HSCT recipients seem to carry mainly gB1 and gB2 CMV genotype.

Dataset Information

Pulmonary cytomegalovirus (CMV) DNA shedding in allogeneic hematopoietic stem cell transplant recipients: Implications for the diagnosis of CMV pneumonia.

Objectives

Methods

Results

Conclusions

Publications

Pulmonary cytomegalovirus (CMV) DNA shedding in allogeneic hematopoietic stem cell transplant recipients: Implications for the diagnosis of CMV pneumonia.

Similar Datasets

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