key: cord-1042373-6yr14yk3 authors: Mowrer, Clayton; Lee, Brian R.; Goyal, Rakesh; Selvarangan, Rangaraj; Schuster, Jennifer E. title: Outcome of children with rhinovirus detection prior to allogeneic hematopoietic cell transplant date: 2018-10-19 journal: Pediatr Transplant DOI: 10.1111/petr.13301 sha: e3d93c90c43d684da2d95aca23544157bbeca05d doc_id: 1042373 cord_uid: 6yr14yk3 Rhinoviruses are commonly detected in symptomatic and asymptomatic children prior to HCT. Unlike pre‐HCT detection of other respiratory viruses, it is not known whether RV detection, with or without clinical symptoms, is associated with worse outcomes in children post‐HCT. In a retrospective study of children undergoing allogeneic HCT from January 2009 to February 2015, 91 children underwent allogeneic HCT, and 62 children had RPP testing within 30 days pre‐HCT. Fifty‐six (90%) children had either no pathogen (n = 34, 55%) or single RV detection (n = 22, 35%), which was the most common pathogen identified. Compared with virus negative children, children with pre‐HCT RV detection were not more likely to require ventilated support and did not have longer length of stay, higher mortality, or less days alive and out of the hospital within the first 100 days post‐HCT. In a secondary analysis of all 56 patients with RPP testing and no pathogen or RV alone detected, the seven children with LRTI had less days alive and out of the hospital within the first 100 days post‐HCT compared with the 49 children who were either asymptomatic or had URTI (10 vs 60 days, P = 0.002). In a bootstrapped regression model, presence of LRTI, not RV detection, was significantly associated with decreased days alive and out of the hospital within the first 100 days post‐HCT. Thus, pre‐HCT detection of RV, without associated LRTI, does not always warrant HCT delay. are lacking, despite the frequency of RV detection. 8 Existing data, predominantly based on adult studies, are conflicting as to whether RV detection in the pre-HCT period results in worse outcomes. 3, 9 Pathogen detection often leads to HCT delay due to risk of URTI progressing to LRTI, respiratory failure, and death. 10, 11 The optimal length of HCT delay is unknown, and continued detection of RV by PCR may represent prolonged viral shedding. 13 Thus, pre-HCT RV detection may lead to unnecessary delay of HCT, which can result in worse outcomes or oncologic relapse. A RPP, a multiplex PCR assay, became available at Children's Mercy Kansas City in December 2008, and the test was offered as part of the pre-HCT evaluation. We aim to determine the prevalence of RV identified pre-allogeneic HCT in children and compare outcomes of children with RV detection to children without viral detection and determine the association of clinical symptoms, or lack thereof, with patient outcomes. We conducted a retrospective study of subjects undergoing allogeneic HCT from January 1, 2009 to February 15, 2015 at Children's Mercy Kansas City who had RPP testing within 30 days prior to HCT. Mid-turbinate or nasal aspirate specimens were obtained at the discretion of the HCT physician, for either diagnostic evaluation in symptomatic patients or for pre-HCT surveillance in asymptomatic patients, and tested for clinical purposes. Specimens obtained from January 1, was also offered by the laboratory during this time; however, these specimens were excluded from the study due to poor sensitivity for rhinovirus. Pre-HCT, repeat testing prior to HCT was obtained at the discretion of the treating physician to determine whether viral detection was ongoing. Post-HCT, repeat testing was obtained at the discretion of the treating physician due to the presence of clinical symptoms. No formal policy, other than hospital-wide isolation precautions, exists regarding the management of patients with a positive test result. Demographics, clinical symptoms, virologic testing, laboratory values, imaging, and outcomes were manually abstracted from the electronic medical record and entered into a REDCap database. 14 Subjects were defined as asymptomatic (ie, no provider documentation of signs or symptoms of respiratory illness in the history or physical examination) or symptomatic (ie, provider documentation of historical symptoms or physical examination signs consistent with respiratory illness). Symptomatic subjects included those with URTI (ie, provider documentation or parental report of respiratory symptoms with no or negative pulmonary imaging, including chest radiograph or chest computed tomography) or LRTI (ie, provider documentation or parental report of respiratory symptoms with abnormal pulmonary imaging). All patients had a scheduled HCT date at the time the specimen was obtained, and HCT delay was determined by whether this date was changed and whether this was due to specimen results. Only patients with sole RV detection and virus negative specimens (n = 56) were included in the analysis since the aim was to evaluate outcomes of children with RV. RV-positive and virus negative children were not significantly different in terms of age, gender, or insurance status, but RV-positive children were significantly less likely to be white ( Table 1 ). The majority of children with an immunodeficiency had RV detection, but the difference in underlying disease was not significant overall. Other HCT-related variables, specimen type, and testing platform were not different between the groups. Specimens were obtained a median of 22.0 days (virus negative) and 19.5 days (RV-positive) prior to HCT. Antimicrobial and GVHD prophylactic regimens were not significantly different between the two groups and were not altered based on detection of RV. Of the 56 specimens included in the final analysis, 41 (73%) specimens were obtained from asymptomatic children ( Table 2 ). The majority of both virus negative (n = 28, 82.4%) and RV-positive (n = 13, 59.1%) patients were asymptomatic. Of the 15 symptomatic patients, 12 (80.0%) had pulmonary imaging, which was used for differentiation between upper and LRTI. One (3%) virus negative and seven (32%) RV-positive patients had URTI, and five (15%) virus negative and two (9%) RV-positive patients had LRTI. No significant difference in type of symptoms was noted between virus negative and RV-positive patients ( Figure 1A ). Only one patient, a child with RV LRTI, underwent HCT delay, for 7 days. The virus negative and RV-positive groups had similar rates of ventilated support and length of stay during the initial hospitalization. Within the first 100 days post-HCT, no difference was noted in days alive and out of the hospital, readmission rates, GVHD, relapse rates, or mortality (Table 3) Overall Of A minority of children undergoing HCT had viral cultures, and they were excluded due to poor sensitivity for RV. This is a single site study, so findings may not be generalizable to children at other hospitals with different underlying conditions and chemotherapy protocols. Viruses were not sequenced, so subsequent detection could represent acquisition of a new strain rather than continued shedding. However, the high rates of RV detection in subsequent specimens highlight that waiting until RV is no longer detected may not be a feasible option for children who urgently need HCT. Additionally, RV are indistinguishable from enteroviruses on these commercial assays; however, previous data suggest that >95% are RV. 16 We present data related to the outcome of children with RV Further larger studies are needed to determine the optimal management of these patients. None. The authors deny any conflict of interest. Respiratory virus infections in pediatric hematopoietic stem cell transplantation Respiratory viral infections after bone marrow/peripheral stem-cell transplantation: the Christie hospital experience Clinical outcomes associated with respiratory virus detection before allogeneic hematopoietic stem cell transplant Human rhinovirus species associated with hospitalizations for acute respiratory illness in young US children Impact of human rhinovirus types and viral load on the severity of illness in hospitalized children with lower respiratory tract infections Viral load and sequence analysis reveal the symptom severity, diversity and transmission clusters of rhinovirus infections Human rhinovirus detection in the lower respiratory tract of hematopoietic cell transplant recipients: association with mortality Management of respiratory viral infections in hematopoietic cell transplant recipients and patients with hematologic malignancies Outcomes of hematopoietic SCT recipients with rhinovirus infection: a matched, case-control study Viral disease prevention after hematopoietic cell transplantation Mortality rates of human metapneumovirus and respiratory syncytial virus lower respiratory tract infections in hematopoietic cell transplantation recipients Respiratory virus infections after stem cell transplantation: a prospective study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation Persistent human rhinovirus type C infection of the lower respiratory tract in a pediatric cord blood transplant recipient Research electronic data capture (REDCap) -a metadata-driven methodology and workflow process for providing translational research informatics support Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective Molecular epidemiology of human rhinovirus infections in the pediatric emergency department Outcome of children with rhinovirus detection prior to allogeneic hematopoietic cell transplant