2025+ASTCT指南：造血细胞移植和细胞治疗受者副流感和人偏肺病毒感染的管理

American Society for Transplantation and Cellular Therapy Series #10: Management of Parainfluenza and Human Metapneumovirus Infections in Hematopoietic Cell Transplantation and Cellular Therapy Recipients

Marjorie V. Batista ${ }^{1, *}$ , Firas El Chaer ${ }^{2}$ , Janet A. Englund ${ }^{3}$ , Michael Boeckh ${ }^{4}$ ,Paul A. Carpenter ${ }^{3,5}$ , Sanjeet S. Dadwal ${ }^{6}$ , Alpana Waghmare ${ }^{7}$ , David Navarro ${ }^{8,9}$ ,Hans H. Hirsch ${ }^{10}$ , Jose Luis Pinana ${ }^{11}$ , Genovefa A. Papanicolaou ${ }^{12}$ , Roy F. Chemaly ${ }^{13}$

1 Department of Infectious Diseases, A.C. Camargo Cancer Center, Sao Paulo, Brazil

${ }^{2}$ Miami Cancer Institute, Miami, Florida

${ }^{3}$ Department of Pediatrics, University of Washington, Seattle Children's Research Institute, Seattle, Washington

4 Clinical Research Division, Vaccine and Infectious Disease Division,Fred Hutchinson Cancer Center, and Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, Washington

§ Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington

${ }^{6}$ Division of Infectious Diseases, Department of Medicine, City of Hope National Medical Center, Duarte, California

${ }^{7}$ Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Division of Infectious Diseases, Department of Pediatrics,University of Washington, Seattle Children's Research Institute, Duarte, California

${ }^{8}$ Microbiology Service, Hospital Clinico Universitario de Valencia, INCLIVA Health Research Institute, and Department of

Microbiology, School of Medicine, University of Valencia, Valencia, Spain

${ }^{9}$ CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain

${ }^{10}$ Transplantation $ \&$ Clinical Virology, Department of Biomedicine, Medical Faculty, University of Basel, Basel, Switzerland

${ }^{11}$ Department of Hematology, Hospital Clinico Universitario of Valencia, INCLIVA, Biomedical Research Institute, Valencia, Spain

${ }^{13}$ Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas MD Anderson Cancer Center,Houston,Texas

Article history:Received 10 June 2025 Accepted 11 June 2025

Key Words:Guidelines Hematopoietic cell transplantation Parainfluenza virus Human metapneumovirus

A B S T R A C T

In 2019, The Practice Guidelines Committee of the American Society for Transplantation and Cellular Therapy partnered with its Transplant Infectious Diseases Special Interest Group to update the 2009 compendium-style infectious disease guidelines for hemato-poietic cell transplantation (HCT). The new format is now structured around frequently asked questions (FAQs), concise tables, and figures to better support clinical providers.Here, a panel of experts in HCT and infectious diseases identified relevant FAQs, which they graded based on the strength of clinical practice recommendations and the level of supporting evidence, as described herein. In the ninth set of guidelines in the series, the focus is on parainfluenza virus and human metapneumovirus, with FAQs addressing

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Paramyxovirus Cellular therapy

epidemiology, incidence, clinical manifestations, risk factors, diagnosis, prevention(including vaccines), and therapeutic management in recipients of HCT and chimeric antigen receptor T cells(cellular therapy). Special considerations for pediatric patients,unmet needs, and future research directions are conveyed in the guidelines.

©2025 The Authors. Published by Elsevier Inc. on behalf of The American Society for Transplantation and Cellular Therapy. This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/)

INTRODUCTION

Parainfluenza virus (PIV; types 1 to 4) and human metapneumovirus (hMPV; types A and B)are common causes of seasonal community-acquired respiratory viral infections (RVIs) in hematopoietic cell transplantation (HCT) recipi-ents [1-3]. Lower respiratory tract infections (LRTIs) with PIV or hMPV are associated with increased mortality rates, ranging from 10% to more than 30% [4,5]. The main risk factors for LRTIs and poor outcomes in HCT recipients include advanced age, lymphopenia, smoking his-tory, infection early after transplantation, low albumin level, human leukocyte antigen mis-matching of the donor and recipient, prolonged exposure to corticosteroids, and graft-versus-host disease [1,6,7]. Management of PIV and hMPV infections in immunocompromised patients is mainly supportive; although approved targeted antiviral therapies are lacking, novel treatment strategies are under clinical investigations.

In 2019, The Practice Guidelines Committee and the Transplant Infectious Diseases Special Interest Group of the American Society for Trans-plantation and Cellular Therapy assembled a panel of experts (the authors) on RVIs to identify key challenges in the management of PIV and hMPV infections in HCT recipients. We developed frequently asked questions (FAQs) about clinical practice regarding management of these infec-tions and provided answers to them based on a literature review and discussion among the panel to reach a consensus. We formulated 16 best prac-tices based on a subset of the FAQs and assigned each of them a strength of recommendation plus an evidence-based grading (Table 1) [8].

FAQ 1: What is the Incidence of PIV and hMPV Infection and Its Clinical Relevance in HCT Recipients?

Across age groups, the incidence of PIV infec-tion in HCT recipients is up to 10% versus 3% for hMPV infection [1,2,4,9,10]. In pediatric HCT recipients (2.0 to 9.5 years of age), PIV and hMPV infection rates have been about 3% and about 1%,respectively [2,11,12]. PIV and hMPV infections

are significant causes of morbidity and mortality in HCT recipients due to their predisposition to causing LRTIs [7,8]. The incidence rates for LRTI at diagnosis range from 7\% to 50\% for PIV and from 5\% to 41\% for hMPV [4,9]. A registry study identi-fied that receipt of posttransplant cyclophospha-mide was associated with increased incidence of RVIs regardless of donor type; however, the researchers did not specifically report the inci-dence or mortality rates of PIV and hMPV RVIs[13].

FAQ 2: What is the Seasonality of PIV and hMPV Infection?

Figure 1 depicts the typical seasonality patterns of PIV(by type) and hMPV infections. PIV epidem-ics occur mostly in the spring and early summer months in both the northern and southern hemi-spheres [14]. Different strains of all four PIV types may have some variability in circulation [15-17].PIV-3 is typically the most common type identi-fied with most cases reported in the spring in the northern hemisphere [18,19] and up to 86% of cases reported between May and July in Japan[16,17]. PIV-4 has been less common, with cases reported year-round [15]. In immunocompro-mised patients, including HCT recipients, PIV detection is quite variable throughout the year,but authors reported that PIV-3 detection rates were highest during the spring and summer months [20,21]. The global seasonality of hMPV epidemics is during the late winter and spring in most temperate areas, whereas it is more variable in tropical areas [4,14,18,19,22-24].

Significant changes in the incidence and sea-sonality patterns of RVIs following the social restriction and protective measures such as mask-wearing and increased practice of hand hygiene during the COVID-19 pandemic have been reported $[25-28]$ . These measures correlated with a significant decrease in the circulation of respiratory viruses other than SARS-CoV-2 during the pandemic[29,30]. However, in late 2022, fol-lowing relaxation of mandated protective meas-ures around the globe, both PIV and hMPV re-emerged, with unusual seasonal patterns and

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Table 1

ASTCT Grading Recommendations for PIV and hMPV Infection in HCT Recipients

|Question|Recommendation|Highest Grade*| |---|---|---| |FAQ 4|FAQ 4|FAQ 4| |Are nucleic acid amplification tests or molecular-based assays recommended for PIV and hMPV detection?|Yes|AI| |Is BAL testing recommended in patients with PIV and hMPV infections and abnormal imaging for diagnosing LRTI with PIV and hMPV or other co-patho-gens such as paramyxoviruses and other viruses, bacterial, and fungal patho-gens?|Yes|AII| |FAQs 6,7|FAQs 6,7|FAQs 6,7| |Should the transplant be delayed, and the conditioning regimen deferred for 2 weeks and until symptoms resolution, when PIV or hMPV infection are diag-nosed?|Yes|All| |Should prednisone-equivalent dose be reduced to<1 mg/kg body weight, if clinically feasible, when acute PIV or hMPV infections are diagnosed?|Yes|BII| |If HCT cannot be deferred, should reduced-intensity conditioning, and T cell-replete HCT be considered?|Yes|BIII| |If HCT cannot be deferred, should lympho-depleting agents(eg,antithymocyte globulin) be avoided, if feasible?|Yes|AllII| |FAQs 8,9,11,12|FAQs 8,9,11,12|FAQs 8,9,11,12| |Should antiviral treatment with Ribavirin be considered in the management of PIV and hMPV in HCT recipients?|No|DIII| |Are polyclonal IVIG currently recommended in the management of PIV or hMPV LRTI in HCT recipients?|Optional|CIII| |Is ID consultation recommended when antimicrobial use is considered for co-pathogens detected during PIV or hMPV infections?|Yes|BIII| |Should contact and standard precaution measures be implemented promptly upon clinical suspicion of PIV and hMPV, particularly during the epidemic sea-sons?|Yes|AII| |Is retesting with nasal or nasopharyngeal samples recommended in HCT recip-ients who have clinically recovered from PIV and hMPV or any other respira- tory viral infections?|No|DII| |Should asymptomatic adult transplant candidates be screened for respiratory viruses prior to transplantation?|No|DII| |Should asymptomatic pediatric transplant candidates be screened for respira- tory viruses prior to transplantation?|Optional|CIII| |Are pulmonary function tests recommended 1-2 months after recovery from PIV and hMPV infections to rule out bronchiolitis bloritans syndrome or air- flow decline?|Yes|BII|

ASTCT indicates American Society for Transplantation and Cellular Therapy; IVIG, intravenous immunoglobulins.

* Based on the strength of a recommendation: A= should always be offered, B= should generally be offered, C= is optional,D= should generally not be offered, E= should never be offered. The quality of evidence supporting the recommendation:I= evidence from at least one properly randomized controlled trial; II= evidence from at least one well-designed clinical trial without randomization, from cohort or case-controlled studies(preferably from more than one center), or from multiple time-series or dramatic results from uncontrolled experiments; Ill= evidence from opinions of respected authorities based on clinical experience, descriptive[7].

higher detection rates than in historical data[25-28], with recent return to similar prepan-demic seasonality[31,32].

FAQ 3: What are the Main Clinical Characteristics and Radiological Patterns in HCT Recipients Infected with PIV or hMPV?

The clinical characteristics and radiological pat-terns of PIV and hMPV infections are similar to

those of other RVIs and are depicted in Table 2[33-38].

FAQ 4: How are PIV and hMPV Infections Diagnosed?

The diagnosis of RVIs has improved signifi-cantly with the use of molecular assays that detect single or multiple respiratory viruses in respira-tory specimens. These assays have replaced

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 Figure 1. PIV and hMPV seasonality trends.

Table 2

Clinical and Radiological Patterns of PIV and hMPV Infection in HCT Recipients

|Type of Virus|PIV|hMPV| |---|---|---| |Incubation period (days)|2-6|4-6| |Symptoms in patients with URTIs||| |Runny nose|$\begin{array}{l}\\ \\ \\ \\ \\ \\ \end{array}$|$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \end{array}$| |Nasal congestion and/or sneezing|$\begin{array}{l}\\ \\ \\ \\ \\ \\ \end{array}$|$\begin{array}{l}\\ \\ \\ \\ \\ \\ \\ \end{array}$| |Sinusitis|No|*| |Pharyngitis/laryngitis|$\dagger$|$\dagger$| |Parotitis|*|No| |Headache|No|$\dagger$| |Conjunctivitis|No|*| |Tracheobronchial cough(no pneumonia)||$\dagger$| |Fever(>37.5°C)|$\dagger$|$\dagger$| |LRTI|$\dagger$|$\dagger$| |Median duration of viral shedding, days|17(14-33)|32.0(19.5-47.5)| |Radiological findings|GGO+SCN|GGO+NdO|

GGO indicates ground-glass opacities; NdO, nodular opacities; SCN, scattered centrallobular nodules.

$^{*}\leq 25\%$ .

$\dagger>25\%$ - 50%.

${}^{\ddagger}$ >50%-≤75%.

§>75%; modified from Ref.[35].

traditional diagnostic techniques such as direct immunofluorescence and viral cultures [39,40].Molecular assays have greater sensitivity and specificity and shorter turnaround times for results than the traditional methods, which may facilitate prompt initiation of targeted therapy(when available), reduction in unnecessary antibi-otic use if a specific viral infection is diagnosed[41], prompt implementation of isolation precau-tions, and faster identification of clusters or out-breaks [42,43]. Multiplex PCR assays can detect 20 or more respiratory pathogens in one assay sys-tem, including those not detected by other diag-nostic methods[44,45]. Accordingly, multiplex

PCR assays are recommended for use with immu-nocompromised patients, particularly HCT recipi-ents, with respiratory signs and symptoms(AIII).No Monoplex or dual-plex PCR assays are cur-rently available for detection of PIV and hMPV infections. Furthermore, patients with LRTIs in whom PIV or hMPV is detected in the upper respi-ratory tract should undergo bronchoalveolar lavage(BAL) testing(All). BAL testing is important for confirmation of the etiology of pneumonia and detection of possible co-pathogens as shown in a few studies of immunocompromised patients in which BAL results led to changes in management of LRTI[46].

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FAQ 5: What are the Risk Factors for PIV and hMPV Acquisition, LRTIs, and Mortality?

RVI acquisition occurs via exposure to infected persons or formites. Overall, factors associated with the acquisition of RVIs include male sex, household contact with children younger than 12 years of age[35], allogeneic HCT, cytomegalovirus seropositiv-ity, T cell-depleted transplantation, and engraft-ment failure[36,47,48]. The main risk factors for progression to LRTI are similar to those for most RVIs and include advanced age, lymphopenia, early posttransplant infection, use of a myeloablative conditioning regimen, mismatched donor status,and graft-versus-host disease as summarized in Table 3[6,7,49]. Researchers have evaluated spe-cific risk factors related to RVIs using the immuno-deficiency scoring index(ISI) that was originally developed for respiratory syncytial virus(RSV) in 2014[6,50] to stratify allogeneic HCT recipients into 3 groups according to their risk for RSV LRTI and mortality. Investigators have assessed the ISI and additional novel risk factors[6,7,51] for their association with PIV infection outcomes after allo-geneic HCT[52,53]. In a recent study evaluating novel factors and the ISI in predicting progression RVI to LRTI, patients who had more than one HCT,were at least 40 years old, experienced infection early after HCT(≤30 days), received systemic ste-roids, had hypoalbuminemia, had hyperglycemia,had cytopenia, and had a high ISI score(range, 7 to 12) had increased risk of progression to LRTI in multivariable models[7]. RSV and hMPV consis-tently had greater risk of progression from upper respiratory tract infection(URTI) to LRTI than did

rhinoviruses in the early[6,7] and late[54] alloge-neic HCT periods. The ISI and the presence of at least three risk factors for LRTI, including newly identified risk factors as described above, appear to similarly predict disease progression for several viruses,including PIV and hMPV[7].

Risk factors associated with increased mortality in patients with PIV infections after allogeneic HCT are relapsed and/or refractory underlying malignancy, APACHE II score higher than 15, and receipt of high-dose steroids[55,56]. For hMPV infections, risk factors include use of steroids at the time of LRTI development, use of peripheral or cord blood stem cells as HCT cell sources, and an oxygen requirement greater than 2 L or need for mechanical ventilation at diagnosis[4,56,57].

FAQ 6: What are the Recommendations for Deferring HCT in a Patient Infected with PIV or hMPV?

Testing positive for respiratory viruses, includ-ing PIV and hMPV, prior to administration of a conditioning regimes in(particularly myeloablative conditioning) in symptomatic adult or pediatric HCT recipients is significantly associated with decreased overall survival rates and increased transplant-related mortality[58,59]. Delaying transplantation for 2 weeks with symptom resolu-tion is recommended for most RVIs, including PIV and hMPV infections(AII)[37,59-62], in both adults and children[63,64]. However, other fac-tors must be taken into consideration before rec-ommending this, including the probability of relapse of the underlying disease,the

Table 3

Risk Factors for PIV and hMPV Infections, Progression to LRTIs, and Mortality

|Risk Factors for infection acquisition|All RVIs Exposure to infected persons or fomites, male sex, household contact with children <12 years of age, allo-geneic HCT,CMV seropositivity,T cell-depleted HCT, and engraftment failure [33,33,44,45]|Same for all RVIs|Same for all RVIs $$\begin{array}{l}\\ \\ \\ \\ \\ \\ \end{array}$$| |---|---|---|---| |Risk factors for progression to LRTI|>1 transplant, age ≥40 years, recent HCT(≤30 days),systemic steroids, hypoalbuminemia,hyperglycemia, cytopenia, and high ISI score(range, 7-12)[1,2]|Same for all RVIs plus monocytopenia, co-pathogen detection in blood, and PIV type[1]|Same for all RVIs plus lymphopenia and early onset of hMPV infection after HCT[3]| |Risk factors for mortality|ATG used as part of conditioning regi- men, lower respiratory tract disease, RVI within the first 6 months of transplantation, lymphopenia, and high ISI score(range, 7-12)[6,57,75]|Relapsed or refractory underlying malignancy, APACHE II score >15, and high-dose steroid use [98]|Steroids at the time of LRTI, use of peripheral or cord blood stem cells as cell sources, and oxygen requirement>2 Lor mechanical ventilation at diagnosis [3,76]|

ATG indicates antithymocyte globulin; CMV,cytomegalovirus.

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conditioning regimen, and donor availability [59].If HCT cannot be deferred, nonmyeloablative or reduced-intensity conditioning and T cell-replete HCT should be considered (BII). Use of lymphode-pleting agents such as antithymocyte globulin should be avoided, if feasible (AIII) [59,65-67]. On the other hand, dose reduction for post-transplan-tation use of cyclophosphamide and antithymo-cyte globulin could be considered (CII) [68].

FAQ 7: What are the Recommendations for Reducing Intensity of Immunosuppressive Therapy for HCT Recipients with PIV or hMPV Infections?

Corticosteroid use is a risk factor for poor RVI outcomes [69]. In particular, high-dose corticoste-roids increase the risk of progression to LRTI by 3.5-fold [70] in HCT recipients with PIV infections and mortality by more than threefold for those receiving corticosteroids at more than $2 mg / kg /$ day[69]. However, prednisone-equivalent doses of lower than $1 mg / kg /$ day may not be associated with poorer outcomes [69]. We recommend reduc-tion of systemic immunosuppression when feasi-ble, especially when prednisone-equivalent doses exceed $2 mg / k /$ day(ideally, to $<1 mg / kg /$ day)(BII).

FAQ 8: What are the Prognosis for and Late Pulmonary Complications after PIV and hMPV Infections in HCT Recipients?

The overall mortality rates in HCT recipients with paramyxovirus LRTIs range from 10% to 43%[1-4,11-16,71-73]. Mortality rates specifically associated with PIV LRTIs also vary widely, rang-ing from 13% to 35% [5,73,74] and those for hMPV LRTIs have been as high as 27% [1,49,57,75,76].Increased mortality is likely a result of co-infec-tion with other pathogens at the time of diagnosis,including viruses, bacteria, or fungi, or late alloim-mune lung complications presumably triggered by PIV and hMPV[77].

Early or late pulmonary impairments owing to RVIs include idiopathic pneumonia syndrome,late airflow obstruction, bronchiolitis oblibrans syndrome, and cryptogenic organizing pneumo-nia [2]. In one study, about 50% of patients with prior diagnosis of idiopathic pneumonia syn-drome had detectable viral pathogens in BAL fluid that were identified in stored specimens using multiplex PCR-based assays, although PIV and hMPV were not specifically reported. These com-plications usually develop when RVIs occur just before or early after HCT [78-81]. In addition,LRTI with a respiratory virus detected in the early post-HCT period is associated with substantial

airflow decline in the first year after HCT and increased nonrelapse mortality [81]. On the other hand, PIV and hMPV viral loads in nasopharyngeal swabs have not been correlated with either the presence or severity of pulmonary complications[82,83]. Finally, pulmonary function tests are rec-ommended 1 to 2 months after recovery from PIV and hMPV infections to rule out bronchiolitis obliterans syndrome or airflow decline (BIII).

PHARMACOLOGICAL TREATMENT FAQ 9: What are the Recommendations for Antiviral Treatment and Intravenous Immunoglobulin Therapy in the Management of PIV and hMPV Infections in HCT Recipients?

Licensed antiviral agents for treating PIV or hMPV infections are not currently available. Aerosolized or systemic(oral or intravenous) ribavirin is the only commercially available antiviral drug with in vitro activity against RSV, hMPV, and PIV [84-86].

Retrospective studies of PIV infections in HCT recipients have shown no outcome benefits in terms of mortality when aerosolized or systemic ribavirin with or without intravenous immuno-globulin therapy is given primarily at the LRTI stage and no reduction in PIV shedding [2,5,55,69,73]. In contrast, in a recent retrospective study in Spain that included 230 allogeneic HCT recipients with PIV infections, oral ribavirin given at the URTI stage was associated with less progression to LRTI but with no impact on all-cause or infectious-related mortality, when compared with untreated patients[70]. Clinical data regarding treatment of hMPV infections are confined to small retrospective stud-ies and case reports/series that all failed to show benefits of ribavirin and intravenous immunoglob-ulin for LRTI [1,4,83,87-90]. Currently, and based on scarce data, ribavirin is not recommended for PIV or hMPV infections in HCT recipients (DIII).Based on the expert opinion of our panel, intrave-nous immunoglobulin may be offered to HCT recip-ients with PIV or hMPV LRTIs (CIII) [90].

FAQ 10: Is There a Role for Antimicrobial Therapy in HCT Recipients with PIV or hMPV Infections?

In previous studies, up to 39% of patients with PIV infections had concurrent infections with pathogens detected in BAL, including Pseudomonas aeruginosa, adenovirus or cytomegalovirus, and Aspergillus species [2,91]. The presence of bacterial,viral, or fungal co-infection was associated with a twofold increase in the risk of death [2]. However,the cumulative number of antibiotic days of ther-apy before acquisition of RVIs and the use of

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quinolones(specifically, ciprofloxacin or levofloxca-cin) or antibiotics against anaerobes were indepen-dently associated with increased risk of progression to LRTI, possibly as a consequence of microbiome dysbiosis[41,92-94]. Infectious dis-eases consultation is generally recommended if antimicrobial use is considered for patients with co-pathogens detected during PIV or hMPV infec-tions (BIII).

PIV AND HMPV INFECTION PREVENTION

FAQ 11: What are the Definitions of Community and Nosocomially Acquired PIV and hMPV Infections and the Isolation Precautions for Them in Hospital Settings?

Community-acquired RVI is defined as the pres-ence of at least one of the following: coryza, dys-pnea, cough, sore throat, and/or wheezing before or fewer than 4 days after hospital admission. Nosoco-mial infection is indicated if symptoms begin at least 4 days after hospitalization[53,95]. Table 4

summarizes the current recommendations for infection control strategies for the major respiratory viruses in healthcare settings(AII)[5,96-101]. In contrast, the significance of prolonged viral shed-ding with regard to nosocomial transmission of respiratory viruses[98,99], particularly PIV[102],remains to be determined. Retesting for PIV or hMPV with nasal or nasopharyngeal swabs gener-ally is not recommended for most patients due to insufficient evidence of its effectiveness for infec-tion control purposes or as a test of cure(DII). For patients with RVIs who experience long hospital stays and who become asymptomatic, retesting to determine whether they can be removed from iso-lation could be contemplated(CIII).

FAQ 12: Should Asymptomatic Patients be Screened or Tested for PIV and hMPV Before HCT?

Asymptomatic PIV and hMPV infections may occur in HCT candidates[36,103]. However, no

Table 4

Infection Control Strategies for Seasonal RVIs in Healthcare Settings

|Respiratory Virus|Type of Precaution|Duration^{*}|Comments| |---|---|---|---| |PIV|Contact+ standard|Duration of illness and as long as patients are hospitalized|Viral shedding may be prolonged in immunosup- pressed patients[4,91]. The reliability of antigen or PCR testing in determin-ing whether to remove patients with prolonged hos- pitalization from contact precautions is uncertain.| |hMPV|Contact+ standard|Duration of illness and as long as patients are hospitalized|HAI is reported[92], but the route of transmission is not well established [93]. The route is assumed to be contact transmission with the patient or the patient's environment as for RSV because they are closely related and have similar clinical manifestations and epidemiology. Masks are to be worn by healthcare professionals during isolation according to standard precautions.| |RSV|Contact+ standard|Duration of illness and as long as patients are hospitalized|In immunocompromised patients, extend the dura- tion of contact precautions due to prolonged shed- ding[97]. The reliability of antigen or PCR testing in determining whether to remove patients with pro- longed hospitalization from contact precautions is uncertain. Masks are to be worn by healthcare pro- fessionals during isolation according to standard pre-cautions[93-96].| |Influenza|Contact+ standard|Duration of illness and as long as patients are hospitalized|In severely immunocompromised patients who may shed influenza virus for long periods of time, extend contact precautions due to prolonged shedding|

https://www.cdc.gov/infectioncontrol/guidelines/isolation/index.html(Last updated May 2022).

* For patients with long hospital stays and who become asymptomatic respiratory-wise, removal from isolation could be contemplated with or without retesting.

${}^{\dagger}$ https://www.cdc.gov/infectioncontrol/basics/transmission-based-precautions.html#anchor_1564057963

§ https://www.cdc.gov/infectioncontrol/basics/standard-precautions.html

§ https://www.cdc.gov/flu/professionals/infectioncontrol/healthcaresettings.htm

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studies have demonstrated the value of screening asymptomatic patients to predict disease severity or mortality or its potential impact on transmis-sion of the virus [36,59]. Screening asymptomatic HCT candidates for respiratory viruses is not rec-ommended for adults (DII) but may be warranted for children due to their higher rates of asymp-tomatic infection and mortality associated with pre-HCT RVIs (CIII) [63].

SPECIAL CONSIDERATIONS

FAQ 13: Do PIV and hMPV Infections in Pediatric HCT Recipients Differ from Those in Adults?

The incidence of PIV and hMPV infection in pediatric HCT recipients is similar to that reported in adults(see FAQ 1). On the other hand, one recent study in children demonstrated PIV-1 to 4 in 13 of 134(10%) pre-HCT viral respiratory speci-mens [63]. Nonetheless, pediatric HCT data are limited when compared with adult data. Clinical presentation and risk factors for progression to LRTI appear to be similar in children and adults,including early post-HCT onset of infection; low neutrophil, monocyte, and lymphocyte counts;and corticosteroid therapy before URTI diagnosis[1,74,104].

FAQ 14: What are the Implications of

Respiratory PIV and hMPV Co-infections?

Pulmonary PIV and hMPV co-infections are common in HCT recipients of all ages[5,49,55,72,90], occurring in up to $47 \%$ of them[1,2,5,49,69,105]. These include bacterial (Pseudo-monas species being the most frequent), other viral (mostly human rhinovirus, RSV, and PIV),and fungal (Aspergillus spp. being the most com-mon) infections [105]. Respiratory co-infections were independent predictors of progression from PIV URTI to LRTI within 1 month of diagnosis after adjusting for neutropenia and an APACHE II score of at least 15 [55]. In HCT recipients with PIV-3 LRTIs, the presence of co-infection was associated with increased mortality at 30 and 180 days after HCT [5].

FAQ 15: Are There Any Special Considerations for Chimeric Antigen Receptor T-cell Recipients with PIV or hMPV Infections?

Overall, RVIs are common after chimeric anti-gen receptor (CAR) T-cell therapies, including CD19 CAR-T cell therapy, with reported incidence rates ranging from 23% to 44.7% [106,107]. In patients receiving B-cell maturation antigen-tar-geted CAR T-cell therapy, reported incidence rates are as high as 53% within the first 6 months of

follow-up [108]. The exact incidence rates for PIV and hMPV infection in CAR T-cell therapy recipi-ents are not reported. In general, risk factors for RVIs include grade 3 or higher cytokine release syndrome, use of a lymphodepleting regimen that includes cyclophosphamide or a regimen contain-ing drugs other than cyclophosphamide and flu-darabine, use of corticosteroids for the management of cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome, hypogammaglobulinemia, and prior HCT [106,107,109-112].

FUTURE DIRECTIONS

FAQ 16: What are the Unmet Needs for Therapy for or Prevention of PIV and hMPV Infections?

Currently, approved antiviral agents, monoclo-nal antibodies, and vaccines specific for PIV or hMPV are lacking. Table S1 summarizes com-pleted and ongoing clinical trials of investigational therapies for different RVis, including PIV, RSV,and hMPV infections.

DAS181, a sialidase fusion protein, was evalu-ated in a phase 2 trial comparing the dry powder inhalant form of DAS181 with its nebulized for-mulation or a matching placebo in immunocom-promised patients with PIV LRTI and hypoxia.Although the primary endpoint, the proportion of patients reaching clinical stability survival(defined as returning to room air and survival at day 45 from enrollment) was not met, a posthoc analysis demonstrated that DAS181 may have had a clinical impact and antiviral activity by improv-ing oxygenation and return to room air for highly immunocompromised patients who were not on mechanical ventilation when compared with patients in the placebo arm [93]. An ongoing phase 3 clinical trial is enrolling immunocompro-mised patients with PIV LRTI and hypoxia, with the primary outcome being the percentage of sub-jects who return to room air by day 28 while maintaining stable peripheral oxygen saturation levels (NCT03808922). Currently, no clinical trials of antiviral agents targeting hMPV are being con-ducted.

Although progress in the development of anti-RSV monoclonal antibodies and vaccines has resulted in licensure and use of these agents in healthy populations [113-118], the development of similar products against PIV and hMPV has been slower. Vaccine candidates using live geneti-cally modified viruses or chimeric viruses and mRNA constructs have undergone clinical testing[119-121], new monoclonal antibodies are being developed [70,122-128], and new approaches to

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antiviral therapy using small molecules or antivi-ral agents are being considered [129-134].

Finally, virus-specific T cells from seropositive stem cell donors or banked "off-the-shelf" third-party human leukocyte antigen-matched donors have been used for the prevention and treatment of RVIs [135]. Polyclonal multi-respiratory virus--specific T cells directed against influenza, RSV,hMPV, and PIV-3 are also feasible [135-139], and studies of PIV- and hMPV-specific T cells in HCT recipients have been conducted [138,140]. Such studies support the pursuit of virus-specific T-cell transfer as a possibly effective RVI treatment strategy in HCT recipients [136-139,141].

DIRECTIONS FOR FUTURE CLINICAL TRIALS FOR RVIS

In the context of clinical trials evaluating new preventive or therapeutic measures for RVIs, such as antiviral agents and immunomodulators, sig-nificant challenges arise in selecting the study population, the optimal study design, and the most appropriate efficacy endpoints. A clinical trial framework for evaluating new therapies for RVIs was proposed [142] and includes identifica-tion of patients at the highest risk for complica-tions from RVIs, such as recipients of allogeneic HCI and novel cellular therapies; the optimal time for intervention (72 to 96 hours) after the onset of upper respiratory tract symptoms; and the incorporation of adaptive randomization with multiarm, multistage designs. Using clinical trial designs that compare different interventions with a common control could improve enrollment dur-ing a predetermined period within the same sea-son [143,144]. Additionally, the primary endpoint should focus on progression to LRTI, severe lower respiratory tract complications, return to room air, or changes in forced expiratory volume in 1 second, as these are more clinically relevant prog-nostic markers than viral clearance [142,145].

ACKNOWLEDGMENTS

We thank Don Norwood, Scientific Editor, in the Research Medical Library at the University of Texas MD Anderson Cancer Center, for editing this article.

Financial Disclosure: M.V.B. received research grants paid to his institution from the NIH/NCI(R01), National Council for Scientific and Techno-logical Development, and São Paulo Research Foundation and honoraria/consulting fees from Takeda, Merck& Co., AbbVie, J&J Innovative Medi-cine and Knight Therapeutics. F.E.C. has received institutional research funding from Celgene,

Bristol-Myers Squibb, Amgen, FibroGen, Sumi-tomo Pharma, and AbbVie and is a consultant for the Association of Cancer Care Centers. J.A.E. is a consultant for Ark Biopharmaceutical, AstraZe-neca, Cidara Therapeutics, GSK, Meissa Vaccines,Merck\& Co., Moderna, Pfizer, and Sanofi Pasteur and has received institutional research support from AstraZeneca, GSK, Merck\& Co., and Pfizer.M.B.S.S.D. has received research funding paid to his institution from Ansun Biopharma, Karius,F2G, GeoVax, Merck\& Co., Basilea, and Amplyx Pharmaceuti/Pfizer; is a consultant or advisor for Takeda, Merck\& Co., Ansun Biopharma, Karius,and AseptiScope; and is on the speakers bureau for Karius. A.W. received research grants paid to her institution from Pfizer, Ansun Biopharma,GSK, and Shionogi and has served as a consultant for AstraZeneca, Merck\& Co., Vir Biotechnology,and GSK. H.H.H. is a consultant for AlloVir, Astra-Zeneca, Moderna, and Roche Diagnostics and received speaker honoraria from Astellas, Biotest,Eurofins, and Takeda. R.F.C. received research grants paid to his institution from the NIH/NCI(RO1), Aicuris, Ansun Biopharma, Genentech, Kar-ius, Symbio, Merck\& Co., Oxford Immunotec, Pul-motect, Freestyle, Takeda, and Eurofins Viracor pharma, Merck\& Co./MSD, Oxford Immunotec,Tether, Takeda, Shionogi, Assembly Bio, Integer-Bio,Symbio,InflaRx,Gilead,Pfizer,Moderna, Invy-vid, Eurofins Viracor, and Karius. D.N., P.A.C., J.L.P.,and G.A.P. declare no conflicts of interest.

SUPPLEMENTARY MATERIALS

Supplementary material associated with this article can be found in the online version at doi:10.1016/j.jtct.2025.06.016.

REFERENCES

1.Seo S,Gooley TA,Kuypers JM,et al.Human metapneu-movirus infections following hematopoietic cell trans-plantation: factors associated with disease progression. Clin Infect Dis. 2016;63(2):178-185.https://doi.org/10.1093/cid/ciw284.

2. Ustun C, Slaby J, Shanley RM, et al. Human parain-fluenza virus infection after hematopoietic stem cell transplantation: risk factors, management, mortality,and changes over time. Biol Blood Marrow Transplant.2012;18(10):1580-1588. https://doi.org/10.1016/j.bmt.2012.04.012.

3. Ison MG, Hirsch HH. Community-acquired respiratory viruses in transplant patients: diversity, impact,unmet clinical needs. Clin Microbiol Rev. 2019;32(4):e00042-19.https://doi.org/10.1128/cmr.00042-19.

4. El Chaer F, Shaln DP, Kmeid J, et al. Burden of human metapneumovirus infections in patients with cancer:risk factors and outcomes. Cancer. 2017;123(12):2329-2337.https://doi.org/10.1002/cncr.30599.

M.V. Batista et al./ Transplantation and Cellular Therapy 31(2025) 624-638

633

5. Nichols WG,Corey L,Gooley T, Davis C, Boeckh M. Para-influenza virus infections after hematopoietic stem cell transplantation: risk factors, response to antiviral ther-apy, and effect on transplant outcome. Blood.2001;98(3):573-578.https://doi.org/10.1182/blood.v98.3.573.

6. Khawaja F, Chemaly RF. Predicting risk of progression to lower respiratory tract infection in allogene hematopoietic cell transplant recipients with respira-tory viral infections: where are we now? Bone Marrow Transplant. 2022;57(5):701-702. https://doi.org/10.1038/s41409-022-01616-7.

7. Ogimi C, Xie H, Waghmare A, et al. Novel factors to predict respiratory viral disease progression in alloge-neic hematopoietic cell transplant recipients. Bone Marrow Transplant. 2022;57(4):649-657. https://doi.org/10.1038/s41409-022-01575-z.

8. Carpenter PA, Papanicolaou G, Chemaly RF, Boeckh M,Savani BN. American Society for Transplantation and Cellular Therapy Infectious Disease Guidelines: pref-ace to the series. Transplant Cell Ther. 2021;27(2):103-104.https://doi.org/10.1016/j.jctt.2020.10.004.

9.D'Angelo CR, Kocherginsky M, Pisano J, et al. Incidence and predictors of respiratory viral infections by multi-plex PCR in allogene hematopoietic cell transplant recipients 50 years and older including geriatric assessment. Leuk Lymphoma. 2016;57(8):1807-1813.https://doi.org/10.3109/10428194.2015.1113279.

10. Boeckh M XH, Kuypers J, Leisenring W, Chien J, Jerome K,Englund JA. Progression, Shedding Patterns, and Clini-cal Disease Associated with Respiratory Virus Infections After Allogeneic Hematopoietic Cell Transplantation.New Orleans, LA: American Society of Hematology Annual Meeting;2013.Abstract.2013.

11. Fisher BT, Danziger Isakov L, Sweet LR, et al. A multi-center consortium to define the epidemiology and outcomes of inpatient respiratory viral infections in pediatric hematopoietic cell transplant infections. J Pediatric Infect Dis Soc. 2018;7(4):275-282.https://doi.org/10.1093/jipds/pix051.

12. Kuypers J, Wright N, Corey L, Morrow R. Detection and quantification of human metapneumovirus in pediatric specimens by real-time RT-PCR. J Clin Virol. 2005;33(4):299-305.https://doi.org/10.1016/j.jcv.2004.11.023.

13. Mulroney CM, Abid MB, Bashey A, et al. Incidence and impact of community respiratory viral infections in post-transplant cyclophosphamide-based graft-versus-host disease prophylaxis and haploidentical stem cell trans-plantation. Br J Haematol.2021;194(1):145-157.https://doi.org/10.1111/bjh.117563.

14. Li Y, Reeves RM, Wang X, et al. Global patterns in monthly activity of influenza virus, respiratory syncytial virus, paraflunova virus, and metapenumovirus: a sys-tematic analysis. Lancet Glob Health. 2019;7(8):e1031-e1045.https://doi.org/10.1016/s2214-109x(19)30264-5.

15. Frost HM, Robinson CC, Dominguez SR. Epidemiology and clinical presentation of parainflue type 4 in children: a 3-year comparative study to parainfluen use types 1-3. J Infect Dis. 2013;209(5):695-702. https://doi.org/10.1093/indfs/jit552.

16. Mizuta K, Abiko C, Aoki Y, et al. Epidemiology of para-influenza virus types 1,2 and 3 infections based on virus isolation between 2002 and 2011 in Yamagata,Japan. Microbiol Immunol. 2012;56(12):855-858.https://doi.org/10.1111/j.1348-0421.2012.00507.x.

17. Yano T, Fukuta M, Maeda C, et al. Epidemiological investigation and seroprevalence of human parain-fluenza virus in Mie Prefecture in Japan during 2009-2013.Jpn J Infect Dis.2014;67(6):506-508.

18. Lam TT, Tang JW, Lai FY, et al. Comparative global epi-demiology of influenza, respiratory syncytial and para-influenza viruses, 2010-2015. J Infect. 2019;79(4):373-382.https://doi.org/10.1016/j.jinf.2019.07.008.

19. Maykowski P, Smithgall M, Zachariah P, et al. Season-ality and clinical impact of human parainfluenza viruses. Influence Other Respir Viruses. 2018;12(6):706-716.https://doi.org/10.1111/irv.12597.

20. Godoy C, Peremiguel-Trillas P, Andrés C, et al. A molecular epidemiological study of human parain-fluenza virus type 3 at a tertiary university hospital during 2013-2015 in Catalonia, Spain. Diagn Microbiol Infect Dis. 2016;86(2):153-159. https://doi.org/10.1016/j.diagmicrobio.2016.07.023.

21. Hakim H, Dallas R, Zhou Y, et al. Acute respiratory infections in children and adolescents with acute lym-phoblastic leukemia. Cancer. 2016;122(5):798-805.https://doi.org/10.1002/cncr.29833.

22.Kaida A, Iritani N, Kubo H, Shiomi M, Kohdera U, Mur-akami T. Seasonal distribution and phylogenetic anal-ysis of human metapneumovirus among children in Osaka City, Japan. J Clin Virol. 2006;35(4):394-399.https://doi.org/10.1016/j.jcv.2005.12.009.

23. Osterhaus A, Fouchier R. Human metapneumovirus in the community. Lancet. 2003;361(9361):890-891.https://doi.org/10.1016/s0140-6736(03)12785-7.

24. Wang L,Allen J, Diong C,et al. Respiratory virus infection after allogeneic hematopoietic stem cell transplant in a tropical center: predictive value of the immunodefi-ciency scoring index. Transpl Infect Dis. 2017;19(3):e12693.https://doi.org/10.1111/tid.12693.

25. Wu Y,Zhou J,Shu T,Li W,Shang S,Du L.Epidemiologi-cal study of post-pandemic pediatric common respira-tory pathogens using multiplex detection. Virol J.2024;21(1):168. https://doi.org/10.1186/s12985-024-02441-8.

26.Alzaydi M, Alosaimi A, Alghamdi AA, et al. Changes in seasonal respiratory viral infections among pediatric population around the COVID-19 pandemic; 2019-2023. Eur J Clin Microbiol Infect Dis. 2024;43(8):1589-1596.https://doi.org/10.1007/s10096-024-04860-5.

27. Cho HJ, Rhee JE, Karg D, et al. Epidemiology of respira-tory viruses in Korean children before and after the COVID-19 pandemic: a prospective study from national surveillance system. J Korean Med Sci. 2024;39(19):e171.https://doi.org/10.3346/jkms.2024.39.e171.

28.Cui AL, Zhu Z, Mao NY, et al.[Analysis of common viral infection in surveillance cases of febrile respiratory syndrome in 9 provinces in 2009 from 2009 to 2021].Xian Dai Yu Fang Yi Xue.2022;56(7):912-918. https://doi.org/10.3760/cma.j.cn112150-20220228-00184.

29. Shi Hj, Kim NY, Eom SA, et al. Effects of non-pharma-cological interventions on respiratory viruses other than SARS-CoV-2: analysis of laboratory surveillance and literature review from 2018 to 2021. J Korean Med Sci.2022;37(21):e172. https://doi.org/10.3346/jjkms.2022.37.e172.

30. Engels G, Sack J, Weissbrich B, et al. Very low inci-dence of SARS-CoV-2, influenza and RSV but high incidence of rhino-, adeno- and endemic coronavi-ruses in children with acute respiratory infection in primary care pediatric practices during the second and third wave of the SARS-CoV-2 pandemic.Pediatr Infect Dis J. 2022;41(4):e146-e148. https://doi.org/10.1097/inf.000000000003460.

31.CDC, Human metapneumovirus. Accessed March11,2025. https://www.cdc.gov/human-metapneumovivi usab about/index.html.

634

M.V. Batista et al. Transplantation and Cellular Therapy 31 (2025) 624-638

32. Kuang L, Xu T, Wang C, et al. Changes in the epidemio-logical patterns of respiratory syncytial virus and human metapumovirus infection among pediatric patients and their correlation with severe cases: a long-term retrospective study. Front Cell Infect Micro-biol. 2024;14:1435294. https://doi.org/10.3389/fcimb.2024.1435294.

33. Kumar D, Husain S, Chen MH, et al. A prospective molec-ular surveillance study evaluating the clinical impact of community-acquired respiratory viruses in lung trans-plant recipients. Transplantation. 2010;89(8):1028-1033.https://doi.org/10.1097/TP.0b013e3181d05a71.

34. Lessler J, Reich NG, Brookmeyer R, Perl TM, Nelson KE,Cummings DA. Incubation periods of acute respiratory viral infections: a systematic review. Lancet Infect Dis.2009;9(5):291-300. https://doi.org/10.1016/s1473-3099(09)70069-6.

35. Martino R, Porras RP, Rabella N, et al. Prospective study of the incidence, clinical features, and outcome of symp-tomatic upper and lower respiratory tract infections by respiratory viruses in adult recipients of hematopoietic stem cell transplants for hematologic mechanisms for hematologic blood Blood Marrow Transplant.2005;11(10):781-796.https://doi.org/10.1016/j.bbmt.2005.07.007.

36. Peck AJ, Englund JA, Kuypers J, et al. Respiratory virus infection among hematopoietic cell transplant recipi-ents: evidence for asymptomatic parainfluenza virus infection. Blood. 2007;110(5):1681-1688. https://doi.org/10.1182/blood-2006-12-060343.

37. Templeton KE, Bredius RG, Schinglet SAa, Claas EC, Vos-sen JM, Kroes AC. Parainfluenza virus 3 infection pre- and post-haematopoietic stem cell transplantation: re-infection or persistence? J Clin Virol. 2004;29(4):320-322. https://doi.org/10.1016/s1386-6532(03)00215-4.

38. Batista MV,El Haddad L, Chemaly RF. Paramyxovirus infections in hematopoietic cell transplant recipients.Curr Opin Infect Dis. 2018;31(6):542-552. https://doi.org/10.1097/qco.0000000000000503.

39. Arbeville S, Thonen-Kerr E, Ferrieri P. Prospective and retrospective evaluation of the performance of the FDA-approved cepheid Xpert Flu/RSV XC assay. Lab Med.2017;48(4):e53-e56. https://doi.org/10.1093/libmed/lmx038.

40. Hanson KE, Couturier MR. Multiplexed molecular diagnostics for respiratory, gastrointestinal, and cen-tral nervous system infections. Clin Infect Dis. 2016;63(10):1361-1367. https://doi.org/10.1093/cid/ciw494.

41. Ogimi C, Krantz EM, Golob JL,et al. Antibiotic exposure prior to respiratory viral infection is associated with progression to lower respiratory tract disease in allo-geneic hematopoietic cell transplant recipients. Biol Blood Marrow Transplant. 2018;24(11):2293-2301.https://doi.org/10.1016/j.bbmt.2018.05.016.

42. Echavaria M, Marcone DN, Querci M, et al. Clinical impact of rapid molecular detection of respiratory pathogens in patients with acute respiratory infection.J Clin Virol.2018;108:90-95.https://doi.org/10.1016/j.jcv.2018.09.009.

43. Kelly SG, Metzger K, Bolon MK, et al. Respiratory syn-cyctial virus outbreak on an adult stem cell transplant unit. Am J Infect Control. 2016(84:99)122-1026.https://doi.org/10.1016/j.ajic.2016.03.075.

44.Leber AL, Everhart K, Daly JA, et al. Multicenter evalua-tion of BioFire FilmArray respiratory panel 2 for detec-tion of viruses and bacteria in nasopharyngeal swab samples. J Clin Microbiol. 2018;56(6):e01945-17.https://doi.org/10.1128/jcm.01945-17.

45. van den Hoogen BG, de Jong JC, Groen J, et al. A newly discovered human pneumovirus isolated from young children with respiratory tract disease. Nat Med.2001;7(6):719-724.https://doi.org/10.1038/89098.

46. Jorge L, Torres D, Languasco A, et al. Clinical usefulness of bronchoalveolar lavage in the management of pul-monary infiltrates in adults with hematological malig-nancies and stem cell transplantation. Mediterr J Hematol Infect Dis. 2020;12(1):e2020025. https://doi.org/10.4084/mjhid.2020.025.

47. Nichols WG, Gooley T, Boeckh M. Community-acquired respiratory syncytial virus and parainfluenza virus infections after hematopoietic stem cell trans-plantation: the Fred Hutchinson Cancer Research Cen-ter experience. Biol Blood Marrow Transplant. 2001;7(suppl):11s-15s. https://doi.org/10.1053/bbmt.2001.v7.pm11777098.

48. Schiffer JT, Kirby K, Sandmaier B, Storb R, Corey L,Boeckh M. Timing and severity of community acquired respiratory virus infections after myeloablative versus non-myeloablative hematopoietic stem cell transplan-tation. Haematologica.2009;94(8):1101-1108. https://doi.org/10.3324/haematol.2008.003186.

49. Pinana JL, Tridello G, Xhaard A, et al. Upper and/or lower respiratory tract infection caused by human metatopneumovirus after allogeneic hematopoietic stem cell transport administration. J Infect Dis. 2024;229(1):83-94. https://doi.org/10.1093/infdis/jiad268.

50.Shah DP,Chantoji SS,Ariza-Heredia EJ,et al.Immuno-deficiency scoring index to predict poor outcomes in hematopoietic cell transplant recipients with RSV infections. Blood. 2014;123(21):3263-3268. https://doi.org/10.1182/blood-2013-12-541359.

51. Ogimi C, Xie H, Waghmare A, et al. Correction: novel factors to predict respiratory viral disease progression in allogeneic hematopoietic cell transplant recipients.Bone Marrow Transplant. 2024;59(12):1790. https://doi.org/10.1038/s41409-024-02418-9.

52. Pinana JL, Hernandez-Boluda JC, Calabuig M, et al. A risk-adapted approach to treating respiratory syncy-tial virus and human parainfluenza virus in allogeneic stem cell transplantation recipients with oral ribavirin therapy: a pilot study. Transpl Infect Dis. 2017;19(4):e01945-17.https://doi.org/10.1111/tid.12729.

53. Hirsch HH, Martino R, Ward KN, Boeckh M, Einsele H,Jungman P. Fourth European Conference on Infec-tions in Leukaemia(ECIL-4): guidelines for diagnosis and treatment of human respiratory syncytial virus,parainfluenza virus, metapneumovirus, rhinovirus,and coronavirus. Clin Infect Dis. 2013;56(2):258-266.https://doi.org/10.1093/cid/cis844.

54. Pinana JL, Carbonell-Asins JA, Gómez D, et al. Commu-nity-acquired respiratory virus infections: a threat to long-term survivors after allogeneic stem cell trans-plant? Clin Infect Dis. 2024:ciae602. https://doi.org/10.1093/cid/ciae602.

55.Chemaly RF, Hannod S, Rathod DB, et al. The charac-teristics and outcomes of parainfluenza virus infec-tions in 200 patients with leukemia or recipients of hematopoietic stem cell transplantation. Blood.2012;119(12):2738-2745. https://doi.org/10.1182/blood-2011-08-371112. quiz 2969.

56. Pinana JL, Pérez A, Montoro J,et al. The effect of timing on community acquired respiratory virus infection mortality during the first year after allogeneic hematopoietic stem cell transplantation: a prospective epidemiological survey. Bone Marrow Transplantation.

M.V. Batista et al./ Transplantation and Cellular Therapy 31(2025) 624-638

635

2020;55(2):431-440. https://doi.org/10.1038/s41409-019-0698-7.

57. Shah DP, Shah PK, Azzi JM, El Chaer F, Chemaly RF.Human metapeunovirus infections in hematopoietic cell transplant recipients and hematologic malignancy patients: a systematic review. Cancer Lett. 2016;379(1):100-106. https://doi.org/10.1016/j.canlet.2016.05.035.

58. Ottaviano G, Lucchini G, Breuer J. et al. Delaying hae-matopoietic stem cell transplantation in children with viral respiratory infections reduces transplant-related mortality. Br J Haematol.2019.https://doi.org/10.1111/bjh.16216.

59. Campbell AP, Guthrie KA, Englund JA, et al. Clinical outcomes associated with respiratory virus detection before allegogene hematopoietic stem cell transplant.Clin Infect Dis. 2015;61(2):192-202. https://doi.org/10.1093/cid/civ272.

60. Mowrer C, Lee BR, Goyal R, Selvarangan R, Schuster JE. Outcome of children with rhinovirus detection prior to allogeneic hematopoietic cell transplant. Pediatr Trans-plant.2018;22(8):e13301.https://doi.org/10.1111/petr.13301.

61. Abandeh H, Lustberg M, Devine S, Elder D, Andrits L,Martin SI. Outcomes of hematopoietic SCT recipients with rhinovirus infection: a matched, case-control study. Bone Marrow Transplant. 2013;48(12):1554-1557. https://doi.org/10.1038/bmt.2013.100.

62. Peck AJ, Corey R, Boehch M. Pretransplant respi-ratory syncytial virus infection: impact of a strategy to delay transplantation. Clin Infect Dis. 2004;39(5):673-680. https://doi.org/10.1086/422994.

63. Kim SR, Nordlander A, Xie H, et al. The impact of pre-transplant respiratory virus detection on posttrans-plant outcomes in children undergoing hematopoietic cell transplantation. Clin Infect Dis. 2024;79(3):761-771.https://doi.org/10.1093/cid/ciae216.

64. Kim SR, Waghmare A, Hijano DR. Approach to hematopoietic cell transplant candidates with respira-tory viral detection. Front Pediatr. 2023;11:1339239.https://doi.org/10.3389/fped.2023.1339239.

65. Admiral R, Nierkens S, de Witte MA, et al. Association between anti-thymyctome globulin exposure and sur-vival outcomes in adult unrelated haemopoietic cell transplantation: a multicentre, retrospective, pharma-codynamic cohort analysis. Lancet Haematol. 2017;4(4):e183-e191.https://doi.org/10.1016/s2352-3026(17)30029-7.

66. Ciceri F, Bonini C, Stanghelli MT, et al. Infusion of suicide-gene-engineered donor lymphocytes after family haploidentical haemopoietic stem-cell trans-plantation for leukaemia (the TK007 trial): a non-randomised phase I-II study. Lancet Oncol. 2009;10(5):489-500. https://doi.org/10.1016/s1470-2045(09)70074-9.

67. Zhou X, Dotti G, Krance A, et al. Inducible caspase-9 suicide gene controls adverse effects from alloreplete T cells after haploidentical stem cell transplantation.Blood.2015;125(26):4103-4113. https://doi.org/10.1182/blood-2015-02-628354.

68.Dulery R,Malard F, Brissot et E, al.Reduced post-trans-plant cyclophosphamide dose with antithymocyte globulin in peripheral blood stem cell haploidentical transplantation. Bone Marrow Transplant. 2023:58(11):1215-1222.https://doi.org/10.1038/s41409-023-02085-2.

69. Seo S, Xie H, Campbell AP, et al. Parainfluenza virus lower respiratory tract disease after hematopoietic

cell transplant: viral detection in the lung predicts outcome. Clin Infect Dis. 2014;58(10):1357-1368.https://doi.org/10.1093/cid/ciu134.

70. Pérez A, Montoro J, Chorao P, et al. Outcome of human parainfluenza virus infection in allogeneic stem cell transplantation recipients: possible impact of ribavirin therapy.Infection.2024;52(5):1941-1952. https://doi.org/10.1007/s15010-024-02213-0.

71. Chemalye RF, Shah DP, Boeckh MJ. Management of respiratory viral infections in hematopoietic cell trans-plant recipients and patients with hematologic malig-nancies. Clin Infect Dis. 2014;59(suppl 5):S344-S351.https://doi.org/10.1093/cid/ciu623.

72. Renaud C,Xie H,Seo S,et al. Mortality rates of human metapneumovirus and respiratory syncytial virus lower respiratory tract infections in hematopoietic cell transplantation recipients. Biol Blood Marrow Transplant. 2013;19(8):1220-1226. https://doi.org/10.1016/j.bbmt.2013.05.005.

73. Shah DP, Shah PK, Azzi JM, Chemaly RF. Parainfluenza virus infections in hematopoietic cell transplant recip-ated virus and hematologic malignancy patients: a system-atic review. Cancer Lett.2016;370(2):358-364.https://doi.org/10.1016/j.canlet.2015.11.014.

74. Seo S, Xie H, Leisenring WM, et al. Risk factors for par-ainfluenza virus lower respiratory tract disease after hematopoietic cell transplantation. Biol Blood Marrow Transplant.2019;25(1):163-171.https://doi.org/10.1016/j.bbmt.2018.08.021.

75. Renaud C, Campbell AP. Changing epidemiology of respiratory viral infections in hematopoietic cell trans-plant recipients and solid organ transplant recipients.Curr Opin Infect Dis. 2011;24(4):333-343. https://doi.org/10.1097/QCO.01b013e3283480440.

76. Williams JV, Martino R, Rabella N, et al. A prospective study comparing human metapenumovirus with other respiratory viruses in adults with hematologic malignancies and respiratory tract infections. J Infect Dis.2005;192(6):1061-1065. https://doi.org/10.1086/432732.

77. Ustun C, Slaby J, Shanley RM, et al. Human parain-fluenza virus infection after hematopoietic stem cell transplantation: risak factors, management, mortality,and changes over time. Biol Blood Marrow Transplant.2012;18(10):1580-1588.https://doi.org/10.1016/j.bmt.2012.04.012.

78. Erard V,Chien JW,Kim HW,et al.Airflow decline after myeloablative allgeneic hematopoietic cell trans-plantation: the role of community respiratory viruses.J Infect Dis.2006;193(12):1619-1625.https://doi.org/10.1086/504628.

79. Versluys AB, Rossen JW, van Ewijk B, Schuurman R,Bierings MB, Boels JJ. Strong association between respiratory viral infection early after hematopoietic stem cell transplantation and the development of life-threatening acute and chronic alloimmune lung syn-dromes. Biol Blood Marrow Transplant. 2010;16(6):782-791.https://doi.org/10.1016/j.bbmt.2009.12.534.

80. Versluys B, Bierings M, Murk JL, et al. Infection with a respiratory virus before hematopoietic cell trans-tation is associated with alloimmune-mediated lung syndromes. J Allergy Clin Immunol. 2018;141(2):697-703.e8.https://doi.org/10.1016/j.jaci.2017.03.055.

81. Sheshadri A, Chemaly RF, Alousi AM, et al. Pulmonary impairment after respiratory viral infections is associ-ated with high mortality in allogeneic hematopoietic cell transplant

636

M.V. Batista et al./ Transplantation and Cellular Therapy 31(2025) 624-638

Transplant. 2019;25(4):800-809. https://doi.org/10.1016/j.bbmt.2018.11.022.

82. Camargo JF, Kimble E, Rosa R, et al. Impact of cytomeg-alovirus viral load on probability of spontaneous clear-ance and response to preemptive therapy in allogeneic stem cell transplantation recipients. Biol Blood Marrow Transplant.2018;24(4):806-814.https://doi.org/10.1016/j.bbmt.2017.11.038.

83. Akhmedov M, Wais S, Vala E, et al. Respiratory syncy-tial virus and human metapneumovirus after alloge-neic hematopoietic stem cell transplantation: impact of the immunodeficiency scoring index, viral load, and ribavirin treatment on the outcomes. Transpl Infect Dis. 2020;22(4):e13276. https://doi.org/10.1111/tid.13276.

84. Graci JD, Cameron CE. Mechanisms of action of ribavi-rin against distinct viruses. Rev Med Virol. 2006;16(1):37-48.https://doi.org/10.1002/rmv.483.

85. Hamelin ME, Prince GA, Boivin G. Effect of ribavir and glucocorticoid treatment in a mouse model of human metapunovirus infection. Antimicrob Agents Chemother.2006;50(2):774-777. https://doi.org/10.1128/aac.50.2.774-777.2006.

86. Leyssen P, Balzarini J, De Clercq E, Nyets J. The pre-dominant mechanism by which ribavirins exerts and para-antiviral activity in vitro against flaviruses and para-myoxurivies in vitro by against flaviruses and para-dydrogenase. J Virol. 2005;79(3):1943-1947. https://doi.org/10.1128/jvi.79.3.1943-1947.2005.

87. Shahda S, Carlos WG, Kiel PJ, Khan B, Hage CA. The human metapneumovirus: a case series and review of the literature. Transpl Infect Dis. 2011;13(3):324-328.https://doi.org/10.1111/j.1399-3062.2010.00575.x.

88.Wyde PR, Chetty SN J, Jewell AM, Boivin G, Piedra PA.Comparison of the inhibition of human metapneumemo-virus and respiratory syncytial virus by ribavirin and immune serum globulin in vitro. Antiviral Res. 2003;60(1):51-59.https://doi.org/10.1016/s0166-3542(03)00153-0.

89. Hoppe BP, de Jongh E, Griffioen-Keijzer A, Zijlstra-Baal-bergen JM, IJ EP, Baboe F. Human metapneumovirus in haematopoietic stem cell transplantation recipients: a case series and review of the diagnostic and therapeutic approach. Neth J Med.2016;74(8):336-341.

90. Spahr Y, Tschudin-Sutter S, Baettig V, et al. Community-acquired respiratory paramxyxovirus infection after allo-geneic hematopoietic cell transplantation: a single-cen-ter experience. Open Forum Infect Dis.2018;5(5):ofy077.https://doi.org/10.1093/ofid/ofy077.

91. Campbell AP, Chien JW, Kuypers J, et al. Respiratory virus pneumonia after hematopoietic cell transplanta-tion (HCT): associations between viral load in bron-choalveolar lavage samples, viral RNA detection in serum samples, and clinical outcomes of HCT. J Infect Dis.2010;201(9):1404-1413. https://doi.org/10.1086/651662.

92. Doan T, Arzika AM, Ray KJ, et al. Gut microbial diver-sity in antibiotic-naive children after systemic antibi-otic exposure: a randomized controlled trial. Clin Infect Dis. 2017;64(9):1147-1153. https://doi.org/10.1093/cid/cix141.

93. Whangbo J, Ritz J, Bhatt A. Antibiotic-mediated modi-fication of the intestinal microbiome in allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant.2017;52(2):183-190.https://doi.org/10.1038/bmt.2016.206.

94. Ogimi C, Krantz EM, Golob JL, et al. Exposure to antibi-otics with anaerobic activity before respiratory viral

infection is associated with respiratory disease pro-gression after hematopoietic cell transplant. Bone Mar-row Transplant. 2022;57(12):1765-1773. https://doi.org/10.1038/s41409-022-01790-8.

95. Ong DS, Faber ThE, Klein Klouwenberg PM, et al. Respira torsy crystal virus in critically ill adult patients with community-acquired respiratory failure: a prospective observational study. Clin Microbiol Infect. 2014;20(8):O505-0507.https://doi.org/10.1111/1469-0691.12503.

96. Elizaga J, Olavarria E, Apperley J, Goldman J, Ward K.Parainfluenza virus 3 infection after stem cell trans-plant: relevance to outcome of rapid diagnosis and ribavirin treatment. Clin Infect Dis. 2001;32(3):413-418.https://doi.org/10.1086/318498.

97. Hall CB. Nosocomial respiratory syncytial virus infec-tions: the "Cold War" has not ended. Clin Infect Dis.2000;31(2):590-596.https://doi.org/10.1086/313960.

98. Leclair JM, Freeman J, Sullivan BF, Crowley CM, Gold-mann DA. Prevention of nosocomial respiratory syncy-tial virus infections through compliance with glove and grown soilation precautions. N Engl J Med.1987;317(6):329-334. https://doi.org/10.1056/nejm198708063170601.

99. Madge P, Paton JY, McColl JH, Mackie PL. Prospective controlled study of four infection-control procedures to prevent nosocomial infection with respiratory syn-cytial virus. Lancet. 1992;340(8827):1079-1083.https://doi.org/10.1016/0140-6736(92)93088-5.

100. Mejias A, Chavez-Bueno S, Ramilo O. Human metapneu-virus: a not so new virus. Pediatr Infect Dis J. 2004;23(1):1-7.https://doi.org/10.1097/01.inf.0000105103.60288.0e. quiz 8-10.

101. Adams RH. Preemptive treatment of pediatric bone marrow transplant patients with asymptomatic respi-ratory syncytial virus infection with aerosolized riba-virin. Biol Blood Marrow Transplant. 2001;7(suppl):16s-18s.https://doi.org/10.1053/bbmt.2001.v7.pm1177709.

102.Tabatabai J, Schnitzler P, Prifert C, et al. Parainfluenza virus infections in patients with hematological malig-nancies or stem cell transplantation: analysis of clini-cal characteristics, nosocomial transmission and viral shedding. PLoS One.2022;17(7):e0271756.https://doi.org/10.1371/journal.pone.0271756.

103. Debiaggi M, Canducci F, Sampaolo M, et al. Persistent symptomless human metapenumovirus infection in hematopoietic stem cell transplant recipients. J Infect Dis. 2006;194(4):474-478. https://doi.org/10.1086/505881.

104. Boechk M. The challenge of respiratory virus infec-tions in hematopoietic cell transplant recipients. Br J Haematol.2008;143(4):455-467. https://doi.org/10.1111/j.1365-2141.2008.07295.x.

105. Pinana JL, Gómez MD, Pérez A, et al. Community-acquired respiratory virus lower respiratory tract dis-ease in allogenetic stem cell transplantation recipient:risk factors and mortality from pulmonary virus-bac-terial mixed infections. Transpl Infect Dis. 2018;20(4):e12926.https://doi.org/10.1111/tid.12926.

106. Hill JA, Li D, Hay KA, et al. Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy. Blood. 2018;131(1):121-130.https://doi.org/10.1182/blood-2017-07-793760.

107.Wudhikarn K, Palomba ML, Pennisi M, et al. Infection during the first year in patients treated with CD19 CAR T cells for diffuse large B cell lymphoma. Blood Cancer J. 2020;10(8):79. https://doi.org/10.1038/s41408-020-00346-7.

M.V. Batista et al./ Transplantation and Cellular Therapy 31(2025) 624-638

637

108. Kambhampati S, Sheng Y, Huang CY, et al. Infectious complications in patients with relapsed refractory multiple myeloma after BCMA CAR T-cell therapy.Blood Adv.2022;6(7):2045-2054.https://doi.org/10.1182/bloodadvances.2020004079.

109. Park JH, Romero FA, Taur Y, et al. Cytokine release syn-drome grade as a predictive marker for infections in patients with relapsed or refractory B-cell acute lym-phoblastic leukemia treated with chimeric antigen receptor T cells. Clin Infect Dis. 2018;67(4):533-540.https://doi.org/10.1093/cid/ciy152.

110. Wu X, Cao Z, Chen Z, et al. Infectious complications in pediatric patients undergoing CD19+CD22+ chi-meric antigen receptor T-cell therapy for relapsed/refractory B-lymphoblastic leukemia. Clin Exp Med.2024;24(1):87. https://doi.org/10.1007/s10238-024-01339-7.

111. Jossyula S, Pont MJ, Dasgupta S, et al. Pathogen-specific humoral immunity and infections in B cell maturation antigen-directed chimeric antigen receptor T cell ther-apy recipients with multiple myeloma. Transplant Cell Ther.2022;28(6):304:e1.304.e9.https://doi.org/10.1016/j.jtct.2022.03.005.

112. Vora SB, Waghmare A, England JA, Qu P, Gardner RA,Hill JA. Infectious complications following CD19 chi-meric antigen receptor T-cell therapy for children,adolescents, and young adults. Open Forum Infect Dis.2020;7(5):ofaa121.https://doi.org/10.1093/ofid/ofa121.

113. Britton A, Roper LE, Kotton CN, et al. Use of respiratory syncytial virus vaccines in adults aged ≥60 years:updated recommendations of the advisory committee on immunization practices - United States, 2024.MMMR Morb Mortal Wkly Rep. 2024:73(32):696-702.https://doi.org/10.15585/mmwr.mm7332e1.

114. Wilson E, Goswami J, Baqui AH, et al. Efficacy and safety of an mRNA-based RSV PreF vaccine in older adults. N Engl J Med. 2023;389(24):2233-2244.https://doi.org/10.1056/NEJMoA2307079.

115. Walsh EE, Pérez Marc G, Zareba AM, et al. Efficacy and safety of a bivalent RSV prefusion f vaccine in older adults. N Engl J Med. 2023;388(16):1465-1477.https://doi.org/10.1056/NEJMo2213836.

116. Papi, Ison MG, Langley JM, et al. Respiratory syncy tial virus prefusion f protein vaccine in older adults. N Engl J Med. 2023;388(7):595-608. https://doi.org/10.1056/NEJMoa2209604.

117. Falsey AR, Williams K, Gymopoulou E, et al. Efficacy and safety of an Ad26.RSV-pref-RSV pre protein vacine in older adults. N Engl J Med. 2023;388(7):609-620. https://doi.org/10.1056/NEJm2207566.

118. Jones JM, Fleming-Dutta KE, Prill MM, et al. Use of mirn-seimab for the prevention of respiratory syncytial virus disease among infants and young children: rec-ommendations of the advisory committee on immuni-zation practices- United States, 2023. MMWR Morb Mortal Wkly Rep. 2023;72(34):920-925. https://doi.org/10.15585/mmwr.mm7234a4.

119. Schnyder Ghamloush S, Essink H, Bu H, et al. Safety and immunogenicity of an mRNA-based hMPV/PIV3 combination vaccine in seropositive children. Pedi-atrics 2024;153(6):e202364748. https://doi.org/10.1542/peds.2023-064748.

120. August A, Shaw CA, Lee H, et al. Safety and immunogeunicity of an mRNA-based human metapneumovirus and parainfluenza virus type 3 combined vaccine in healthy adults. Open Forum Infect Dis. 2022;9(7):ofac206.https://doi.org/10.1093/ofac206.

121. Yang CF,Wang CK, Malkin E, et al. Implication of respi-ratory syncytial virus (RSV) F transgene sequence het-erogeneity observed in phase 1 evaluation of MEDI-534, a live attenuated parainfluenza type 3 vectored RSV vaccine. Vaccine. 2013;31(26):2822-2827.https://doi.org/10.1016/j.vaccine.2013.04.006.

122. Gingerich A. Mahoney L, McCormick AL, Miller RJ,Mousa J. Human monoclonal antibodies protect against viral-mediated pneumococcal superinfection.Front Immunol. 2024;15:1364622. https://doi.org/10.3389/fimmu.2024.1364622.

123. Fausthe-Bovendo H, Hamelin ME, Carbonneau J, et al.A candidate therapeutic monoclonal antibody inhibits both HRSV and HMPV replication in mice. Biomedi-cines.2022;10(10):2516. https://doi.org/10.3390/bio-medicines10102516.

124. Schuster JE, Cox RG, Hastings AK, et al. A broadly neu-tralizing human monoclonal antibody exhibits in vivo efficacy against both human metapneumovirus and respiratory syncytial virus. J Infect Dis. 2015;211(2):216-225.https://doi.org/10.1093/infdis/jiu307.

125. Hamelin ME, Couture C, Sackett M, et al. The prophyl-lactic administration of a monoclonal antibody against human metapneumovirus attenuates viral disease and airways hyperresponsiveness in mice. Antivir Ther.2008;13(1):39-46.

126. Williams JV, Chen Z, Cseke G, et al. A recombinant human monoclonal antibody to human metapneumovi-rus fusion protein that neutralizes virus in vitro and is effective therapeutically in vivo. J Virol. 2007;81(15):8315-8324.https://doi.org/10.1128/jvi.00106-07.

127. Ulbrandt ND, Ji H, Patel NK, et al. Isolation and charac-terization of monoclonal antibodies which neutralize human metapneumovirus in vitro and in vivo. J Virol.2006;80(16):7799-7806.https://doi.org/10.1128/jvi.00318-06.

128.Xiao X, Wen Z, Chen Q, et al. Structural characteriza-tion of M8C10, a neutralizing antibody targeting a highly conserved prefusion-specific epitope on the metapneumovirus fusion trimerization interface. J Virol.2023;97(12):e0105223. https://doi.org/10.1128/jvi.01052-23.

129. Dhakal B, D'Souza A, Pasquini M, et al. DAS181 treat-ment of severe parainfluenza virus 3 pneumonia in allogeneic hematopoietic stem cell transplant recipi-ents requiring mechanical ventilation. Case Rep Med.2016;2016:8503275.https://doi.org/10.1155/2016/8503275.

130.Salvatore M., Satlin MJ, Jacobs SE, et al. DAS181 for treatment of parainfluenza virus infections in hemato-poietic stem cell transplant recipients at a single cen-ter. Biol Blood Marrow Transplant. 2016;22(5):965-970. https://doi.org/10.1016/j.bbmt.2016.02.011.

131. Waghmare A, Wagner T, Andrews R, et al. Successful treatment of parainfluenza virus respiratory tract infection with das181 for 4 immunocompromised chil-dren. J Pediatric Infect Dis Soc. 2015;4(2):114-118.https://doi.org/10.1093/jpids/piu039.

132. Chkias S, Mackenzie MR, Gay C,et al. DAS181 treat-ment of hematopoietic stem cell transplant patients with parainfluenza virus lung disease requiring mechanical ventilation. Transpl Infect Dis. 2014;16(1):141-144.https://doi.org/10.1111/tid.12177.

133. Guzman-Suarez BB, Buckley MW, Gilmore ET, et al.Clinical potential of DAS181 for treatment of parain-fluenza 3 infections in transplant recipients. Transpl Infect Dis.2012;114(4):427-433.https://doi.org/10.1111/j.1399-3062.2012.00718.x.

638

M.V. Batista et al./ Transplantation and Cellular Therapy 31(2025) 624-638

134. Chen YB, Driscoll JP, McAfee SL, et al. Treatment of par-ainfluenza 3 infection with DAS181 in a patient after allogeneic stem cell transplantation. Clin Infect Dis.2011;53(7):e77-e80. https://doi.org/10.1093/cid/cir501.

135. Vasileiou S, Turney AM, Kuvalekar M, et al. Rapid gen-eration of multivirus-specific T lymphocytes for the prevention and treatment of respiratory viral infec-tions. Haematologica. 2020;105(1):235-243. https://doi.org/10.3324/haematol.2018.206896.

136. Harris KM, Horn SE, Grant ML, et al. T-cell therapeutics targeting human parainfluenza virus 3 are broadly epi-tope specific and are cross reactive with human parain-fluenza virus 1. Front Immunol. 2020;11:575977. https://doi.org/10.3389/fimmu.2020.575977.

137. Tzannou I, Nicholas SK, Lulla P,et al. Immunologic profil-ing of human metapneumovinus for the development of targeted immunotherapy. J Infect Dis. 2017;216(6):678-687.https://doi.org/10.1093/infdis/jix358.

138. Aguayo-Hiraldo Pl, Arasaratnam RJ, Tzannou I, et al.Characterizing the cellular immune response to para-influenza virus 3. J Infect Dis. 2017;216(2):153-161.https://doi.org/10.1093/infdis/jix203.

139. McLaughlin LP, Lang H, Williams E, et al. Human parainfluen virus-3 can be targeted by rapidly ex vivo expanded T lymphocytes. Cytotherapy.2016;18(12):1515-1524. https://doi.org/10.1016/j.jcyt.2016.08.010.

140. Baugh KA, Tzannou I, Leen AM. Infusion of cytotoxic T lymphocytes for the treatment of viral infections in hematopoetic stem cell transplant patients. Curr Opin Infect Dis. 2018;31(4):292-300. https://doi.org/10.1097/qco.000000000000456.

141. Waghmare A, Englund JA, Boeckh M. Parainfluenza virus 3-specific T cells: opportunity for intervention? J Infect Dis. 2017;216(2):147-149. https://doi.org/10.1093/infdis/jix207.

142. Sassine J, Hirsch HH, Chemaly RF. Clinical trials for treatment of respiratory viral infections in recipients of haematopoietic cell transplantation and cellular therapies: are we on the right path to the finish line?Clin Microbiol Infect. 2024;30(3):270-275. https://doi.org/10.1016/j.cmi.2023.09.013.

143. Chemaly RF, Torres HA, Munsell MF, et al. An adaptive randomized trial of an intermittent dosing schedule of aerosolized ribavirin in patients with cancer and respira-tory syncytial virus infection. J Infect Dis. 2012;206(9):1367-1371.https://doi.org/10.1093/indfs/jis516.

144. Subbiah V. The next generation of evidence-based medicine. Nat Med. 2023;29(1):49-58. https://doi.org/10.1038/s41591-022-02160-z.

145. Waghmare A, Xie H, Kimball L, et al. Supplemental oxygen-free days in hematopoietic cell transplant recipients with respiratory respiratory syncytial virus. J Infect Dis.2017;216(10):1235-1244. https://doi.org/10.1093/indfs/jix390.

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