Supplemental Oxygen–Free Days in Hematopoietic Cell Transplant Recipients With Respiratory Syncytial Virus

Waghmare, Alpana; Kimball, Louise E.; Yi, Jessica; Özkök, Sezen; Leisenring, Wendy; Cheng, Guang‐Shing; Englund, Janet A.; Watkins, Timothy R.; Chien, Jason W.; Boeckh, Michael

doi:10.1093/infdis/jix390

Cited by 19 publications

(23 citation statements)

References 35 publications

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“…9 In contemporary cohorts of HCT recipients with RSV LRTI, the overall mortality ranged from 11%-30%. 3,5,8,10,11 Allo-HCT recipients often have high-risk underlying malignancies and require immunosuppression as compared to auto-HCT recipients. 14 However, we found that mortality was high in all HM patients regardless of HCT status.…”

Section: Discussionmentioning

confidence: 99%

“…Once an RSV diagnosis is confirmed, risk stratification in HM patients is critical given the high cost of therapy with aerosolized ribavirin 7 and high mortality rates after LRTI. 3,5,[8][9][10][11] Prior studies have identified lymphopenia, neutropenia, and RSV detection in lower respiratory samples as important risk factors for mortality after LRTI. 8,[11][12][13] Recognition of individuals at high risk for adverse outcomes could improve the prompt delivery of ribavirin treatment, which may reduce mortality and morbidity.…”

Section: Introductionmentioning

confidence: 99%

“…3,5,[8][9][10][11] Prior studies have identified lymphopenia, neutropenia, and RSV detection in lower respiratory samples as important risk factors for mortality after LRTI. 8,[11][12][13] Recognition of individuals at high risk for adverse outcomes could improve the prompt delivery of ribavirin treatment, which may reduce mortality and morbidity. 9 We previously developed an immunodeficiency scoring index based on clinical characteristics and laboratory parameters to standardize the risk stratification practices of allogeneic HCT (allo-HCT) recipients with RSV upper respiratory tract infection (URTI), a group at high risk for adverse outcomes after RSV Infection.…”

Section: Introductionmentioning

confidence: 99%

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Risk factors for mortality after respiratory syncytial virus lower respiratory tract infection in adults with hematologic malignancies

Vakil

Sheshadri

Faiz

et al. 2018

Transplant Infectious Dis

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Risk factors for mortality after respiratory syncytial virus lower respiratory tract infection in adults with hematologic malignancies

Vakil

Sheshadri

Faiz

et al. 2018

Transplant Infectious Dis

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“…Serum and BAL were routinely tested for Aspergillus with the galactomannan index using the Bio-Rad Platelia Assay (Hercules, CA) [13]. In addition, a multiplex quantitative reverse-transcriptase PCR panel was used to detect 12 respiratory viruses, including influenza A, influenza B, RSV, parainfluenza virus types 1 to 4, adenovirus, human metapneumovirus, coronavirus, rhinovirus, and bocavirus [14]. Invasive fungal infections were defined according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria [15].…”

Section: Definition Of Ipsmentioning

confidence: 99%

Incidence, Risk Factors, and Outcomes of Idiopathic Pneumonia Syndrome after Allogeneic Hematopoietic Cell Transplantation

Wenger

Triplette

Crothers

et al. 2020

Biology of Blood and Marrow Transplantation

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A B S T R A C T Our current knowledge of idiopathic pneumonia syndrome (IPS) predates improved specificity in the diagnosis of IPS and advances in hematopoietic cell transplantation (HCT) and critical care practices. In this study, we describe and update the incidence, risk factors, and outcomes of IPS. We performed a retrospective cohort study of all adults who underwent allogeneic HCT at the Fred Hutchinson Cancer Research Center between 2006 and 2013 (n = 1829). IPS was defined using the National Heart, Lung, and Blood Institute consensus definition: multilobar airspace opacities on chest imaging, absence of lower respiratory tract infection, and hypoxemia. We described IPS incidence and mortality within 120 and 365 days after HCT. We examined conditioning intensity (nonmyeloablative versus myeloablative with high-dose total body irradiation [TBI] versus myeloablative with low-dose TBI) as an IPS risk factor in a time-to-event analysis using Cox models, controlled for age at transplant, HLA matching, stem cell source, and pretransplant Lung function Score (a combined measure of impairment in Forced Expiratory Volume in the first second (FEV 1 ) and Diffusion capacity for carbon monoxide (DLCO)). Among 1829 HCT recipients, 67 fulfilled IPS criteria within 120 days (3.7%). Individuals who developed IPS were more likely to be black/non-Hispanic versus other racial groups and have severe pulmonary impairment but were otherwise similar to participants without IPS. In adjusted models, myeloablative conditioning with high-dose TBI was associated with increased risk of IPS (hazard ratio, 2.5; 95% confidence interval, 1.2 to 5.2). Thirty-one patients (46.3%) with IPS died within the first 120 days of HCT and 47 patients (70.1%) died within 365 days of HCT. In contrast, among the 1762 patients who did not acquire IPS in the first 120 days, 204 (11.6%) died within 120 days of HCT and 510 (29.9%) died within 365 days of HCT. Our findings suggest that although the incidence of IPS may be declining, it remains associated with post-transplant mortality. Future study should focus on early detection and identifying pathologic mediators of IPS to facilitate timely, targeted therapies for those most susceptible to lung injury post-HCT.

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“…from 2003 to 2015, no patients with radiographic abnormalities consistent with LRTI but with RSV detected in upper respiratory tract samples only ("possible" RSV LRTI) died, but 28-day mortality was 26% in HCT recipients with probable or proven RSV LRTI [3].…”

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confidence: 99%

A Phase 2b, Randomized, Double-blind, Placebo-Controlled Multicenter Study Evaluating Antiviral Effects, Pharmacokinetics, Safety, and Tolerability of Presatovir in Hematopoietic Cell Transplant Recipients with Respiratory Syncytial Virus Infection of the Lower Respiratory Tract

Marty

Chemaly

Mullane

et al. 2019

Clinical Infectious Diseases

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Background. Presatovir significantly reduced nasal viral load, signs, and symptoms of respiratory syncytial virus (RSV) infection in a human challenge study. We evaluated presatovir in hematopoietic-cell transplant (HCT) recipients with RSV lower respiratory tract infection (LRTI).Methods. Patients with confirmed RSV in upper and lower respiratory tract and new chest X-ray abnormalities were randomized (1:1), stratified by supplemental oxygen and ribavirin use, to receive oral presatovir 200 mg or placebo every 4 days for 5 doses. The primary endpoint was time-weighted average change in nasal RSV viral load through day 9. Secondary endpoints included supplemental oxygen-free days, incident respiratory failure requiring mechanical ventilation, and all-cause mortality.Results. From January 31, 2015, to March 20, 2017, 60 patients from 17 centers were randomized (31 presatovir, 29 placebo); 59 received study treatment (50 allogeneic, 9 autologous HCT). In the efficacy population (29 presatovir, 28 placebo), presatovir treatment did not significantly reduce time-weighted average change in viral load (−1.12 vs −1.09 log 10 copies/mL; treatment difference −0.02 log 10 copies/mL, 95% confidence interval: −.62, .57; P = .94), median supplemental oxygen-free days (26 vs 28 days, P = .84), incident respiratory failure (10.3 vs 10.7%, P = .98), or all-cause mortality (0 vs 7.1%, P = .19) versus placebo. Adverse events were similar between arms (presatovir 80%, placebo 79%). Resistance-associated substitutions in RSV fusion protein emerged in 6/29 presatovir-treated patients.Conclusions. Presatovir treatment was well tolerated in HCT patients with RSV LRTI but did not improve virologic or clinical outcomes versus placebo. clinical Trials Registration. NCT02254421; EudraCT, #2014-002475-29 Keywords. Presatovir; respiratory syncytial virus; hematopoietic cell transplant; lower respiratory tract infection. Respiratory syncytial virus (RSV) infection is usually associated with respiratory diseases of infants and young children, but RSV lower respiratory tract infection (LRTI) can cause significant morbidity and mortality in adults with predisposing conditions [1]. In recent studies, 16%-27% of hematopoietic-cell transplantation (HCT) recipients initially diagnosed with RSV upper respiratory tract infection (URTI) had LRTI events [2-4]. Mortality rates of up to 60% are reported for RSV LRTI in HCT recipients but appear to be declining [3-7]; however, observed burden of RSV LRTI depends on diagnostic criteria. In cases Downloaded from https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciz1167/5648099 by guest on 23 May 2020

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Supplemental Oxygen–Free Days in Hematopoietic Cell Transplant Recipients With Respiratory Syncytial Virus

Abstract: Confirmation of RSV infection in the lower respiratory tract provides prognostic information that may help prioritize therapies. Supplemental oxygen-free days as a clinical endpoint may allow smaller sample sizes for trials evaluating RSV antivirals.

Cited by 19 publications

References 35 publications

Risk factors for mortality after respiratory syncytial virus lower respiratory tract infection in adults with hematologic malignancies

Risk factors for mortality after respiratory syncytial virus lower respiratory tract infection in adults with hematologic malignancies

Incidence, Risk Factors, and Outcomes of Idiopathic Pneumonia Syndrome after Allogeneic Hematopoietic Cell Transplantation

A Phase 2b, Randomized, Double-blind, Placebo-Controlled Multicenter Study Evaluating Antiviral Effects, Pharmacokinetics, Safety, and Tolerability of Presatovir in Hematopoietic Cell Transplant Recipients with Respiratory Syncytial Virus Infection of the Lower Respiratory Tract

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