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Microbiologic Diagnostic Workup of Acute Respiratory Failure with Pulmonary Infiltrates after Allogeneic Hematopoietic Stem Cell Transplantation: Findings in the Era of Molecular- and Biomarker-Based Assays.

ABSTRACT: Allogeneic hematopoietic stem cell transplantation (HSCT) recipients frequently develop acute respiratory failure (ARF) with pulmonary infiltrates. Molecular- and biomarker-based assays enhance pathogen detection, but data on their yield in this population are scarce. This was a retrospective single-center study of 156 consecutive HSCT recipients admitted to the intensive care unit (ICU) between May 2013 and July 2017. Findings from a microbiologic diagnostic workup using currently available methods on bronchoalveolar lavage (BAL) and blood samples from 66 patients (age, 58 years [range, 45 to 64]; HSCT to ICU, 176 days [range, 85 to 407]) with ARF and pulmonary infiltrates were analyzed. In 47 patients (71%) a causative pathogen was identified (fungal, n?=?28; viral, n?=?26; bacterial, n?=?18). Polymicrobial findings involving several pathogen groups occurred in 20 patients (30%). Culture (12/16, 75%), galactomannan (13/15, 87%), and Aspergillus-PCR (8/9, 89%) from BAL but not serum galactomannan (6/14, 43%) helped to diagnose invasive aspergillosis (n?=?16, 24%). Aspergillus-PCR detected azole resistance in 2 cases. Mucorales was found in 7 patients (11%; BAL culture, n?=?6; Mucorales-PCR, n?=?1). Patients with identified pathogens had higher Simplified Acute Physiology Score II scores (P?=?.049) and inferior ICU survival (6% versus 37%, P?

SUBMITTER: Wohlfarth P

PROVIDER: S-EPMC7110883 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Microbiologic Diagnostic Workup of Acute Respiratory Failure with Pulmonary Infiltrates after Allogeneic Hematopoietic Stem Cell Transplantation: Findings in the Era of Molecular- and Biomarker-Based Assays.

Wohlfarth Philipp P Turki Amin T AT Steinmann Joerg J Fiedler Melanie M Steckel Nina K NK Beelen Dietrich W DW Liebregts Tobias T

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 20180314 8

Allogeneic hematopoietic stem cell transplantation (HSCT) recipients frequently develop acute respiratory failure (ARF) with pulmonary infiltrates. Molecular- and biomarker-based assays enhance pathogen detection, but data on their yield in this population are scarce. This was a retrospective single-center study of 156 consecutive HSCT recipients admitted to the intensive care unit (ICU) between May 2013 and July 2017. Findings from a microbiologic diagnostic workup using currently available met ...[more]

PMID: 29550627

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Project description:Pulmonary complications (PCs) cause significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HCT). Shifts in gut microbiota have been linked to HCT outcomes; however, their effect on PCs is unknown.To investigate whether changes in gut microbiota are associated with PCs after HCT.A single-center observational study was performed on 94 patients who underwent HCT from 2009 to 2011 and who were previously enrolled in a protocol for 16S ribosomal RNA sequencing of fecal microbiota. The primary endpoint, PC, was defined by new abnormal parenchymal findings on chest imaging in the setting of respiratory signs and/or symptoms. Outcomes were collected up to 40 months after transplant. Clinical and microbiota risk factors for PCs and mortality were evaluated using survival analysis.One hundred twelve PCs occurred in 66 (70.2%) subjects. A high comorbidity index (hazard ratio [HR], 2.30; 95% confidence interval [CI], 1.30-4.00; P?=?0.004), fluoroquinolones (HR, 2.29, 95% CI, 1.32-3.98; P?=?0.003), low baseline diversity (HR, 2.63; 95% CI, 1.22-5.32; P?=?0.015), and ?-proteobacteria domination of fecal microbiota (HR, 2.64; 95% CI, 1.10-5.65; P?=?0.031), which included common respiratory pathogens, predicted PCs. In separate analyses, low baseline diversity was associated with PCs that occurred preengraftment (HR, 6.30; 95% CI, 1.42-31.80; P?=?0.016), whereas ?-proteobacteria domination predicted PCs postengraftment (HR, 3.68; 95% CI, 1.49-8.21; P?=?0.006) and overall mortality (HR, 3.52; 95% CI, 1.28-9.21; P?=?0.016). Postengraftment PCs were also independent predictors of death (HR, 2.50; 95% CI, 1.25-5.22; P?=?0.009).This is the first study to demonstrate prospective changes in gut microbiota associated with PCs after HCT. Postengraftment PCs and ?-proteobacteria domination were predictive of mortality. This suggests an adverse relationship between the graft and lung, which is perhaps mediated by bacterial composition in the gut. Further study is warranted.

Project description:Background and objectivesAKI is a major complication of allogeneic hematopoietic stem cell transplantation, increasing risk of nonrelapse mortality. AKI etiology is often ambiguous due to heterogeneity of conditioning/graft versus host disease regimens. To date, graft versus host disease and calcineurin inhibitor effects on AKI are not well defined. We aimed to describe AKI and assess pre-/post-hematopoietic transplant risk factors in a large recent cohort.Design, setting, participants, & measurementsWe performed a single-center, retrospective study of 616 allogeneic hematopoietic cell transplant recipients from 2014 to 2017. We defined AKI and CKD based on Kidney Disease Improving Global Outcomes (KDIGO) criteria and estimated GFR using the Chronic Kidney Disease Epidemiology Collaboration equation. We assessed AKI pre-/post-hematopoietic transplant risk factors using cause-specific Cox regression and association of AKI with CKD outcomes using chi-squared test. AKI was treated as a time-dependent variable in relation to nonrelapse mortality.ResultsIncidence of AKI by day 100 was 64%. Exposure to tacrolimus and other nephrotoxins conferred a higher risk of AKI, but tacrolimus levels were not associated with severity. Reduced-intensity conditioning carried higher AKI risk compared with myeloablative conditioning. Most stage 3 AKIs were due to ischemic acute tubular necrosis and calcineurin inhibitor nephrotoxicity. KRT was initiated in 21 out of 616 patients (3%); of these 21 patients, nine (43%) recovered and five (24%) survived to hospital discharge. T cell-depleted transplants, higher baseline serum albumin, and non-Hispanic ethnicity were associated with lower risk of AKI. CKD developed in 21% (73 of 345) of patients after 12 months. Nonrelapse mortality was higher in those with AKI (hazard ratio, 2.77; 95% confidence interval, 1.8 to 4.27).ConclusionsAKI post-hematopoietic cell transplant remains a major concern. Risk of AKI was higher with exposure to calcineurin inhibitors. T cell-depleted hematopoietic cell transplants and higher serum albumin had lower risk of AKI. Of the patients requiring KRT, 43% recovered kidney function.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_09_07_CJN19801220.mp3.

Project description:BackgroundInfection and graft-versus-host disease (GvHD) are the major causes for mortality and morbidity of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Plasma-derived extracellular vesicles (EVs) contain disease-related proteins, DNAs and RNAs, and have recently been suggested as potential biomarker candidates for transplantation complications. However, EV isolation from small plasma volumes in clinical biomarker studies using conventional methods is challenging. We therefore investigated if EVs isolated by novel automated acoustic trapping could be developed as potential biomarkers for allo-HSCT complications by performing a clinical proof-of-principle study.ResultsPlasma samples were collected from twenty consecutive patients with high-risk/relapsed hematologic malignancies undergoing allo-HSCT before transplantation and post-transplant up to 12 weeks. EVs were isolated from small plasma sample volumes (150 μl) by an automated, acoustofluidic-based particle trapping device, which utilizes a local λ/2 ultrasonic standing wave in a borosilicate glass capillary to capture plasma EVs among pre-seeded polystyrene microbeads through sound scatter interactions. We found that EVs could be reliably isolated from all plasma samples (n = 173) and that EV numbers increased more than 2-fold in the majority of patients after transplantation. Also, sufficient quantities of RNA for downstream microRNA (miRNA) analysis were obtained from all samples and EV miRNA profiles were found to differ from whole plasma profiles. As a proof of principle, expression of platelet-specific miR-142-3p in EVs was shown to correlate with platelet count kinetics after transplantation as expected. Importantly, we identified plasma EV miRNAs that were consistently positively correlated with infection and GvHD, respectively, as well as miRNAs that were consistently negatively correlated with these complications.ConclusionsThis study demonstrates that acoustic enrichment of EVs in a clinical biomarker study setting is feasible and that downstream analysis of acoustically-enriched EVs presents a promising tool for biomarker development in allo-HSCT. Certainly, these findings warrant further exploration in larger studies, which will have significant implications not only for biomarker studies in transplantation but also for the broad field of EV-based biomarker discovery.

Dataset Information

Microbiologic Diagnostic Workup of Acute Respiratory Failure with Pulmonary Infiltrates after Allogeneic Hematopoietic Stem Cell Transplantation: Findings in the Era of Molecular- and Biomarker-Based Assays.

Publications

Microbiologic Diagnostic Workup of Acute Respiratory Failure with Pulmonary Infiltrates after Allogeneic Hematopoietic Stem Cell Transplantation: Findings in the Era of Molecular- and Biomarker-Based Assays.

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