To assess factors associated with outcome in children admitted to paediatric intensive care (PIC) with bronchiolitis. A retrospective study of children admitted to the PICU at St Mary’s Hospital, London with bronchiolitis over a 6-year period (2011–2016). All bronchiolitis admissions < 2 years were included. Data collected particularly noted risk factors for severity, demographics, microbiology and outcome. We compared respiratory syncytial virus (RSV) with non-RSV status. Multivariate analysis was performed. Two hundred seventy-four patients were identified. Median age was 60 days (IQR 28–150 days), 63% were male, 90% were invasively ventilated and 42% were previously healthy. Pre-existing co-morbidities were present in 38%. The most frequently isolated pathogens were RSV (60%) and rhinovirus (26%). Co-infection was present in 45%, most commonly with RSV, rhinovirus and bacterial pathogens. Median length of stay (LOS) was 6 days (IQR 4.75–10). Younger age, prematurity, RSV, co-infection and co-morbidity were identified as significant risk factors for prolonged LOS. Six children died. Five of these had documented co-morbidities.
Conclusion: RSV causes more severe bronchiolitis than other viruses. Nearly half of children admitted to PICU with RSV were previously healthy. Current guidelines for immunoprophylaxis of RSV bronchiolitis should be re-considered.
Donor availability and transplantation-related risks limit the broad use of allogeneic hematopoietic-cell transplantation in patients with transfusion-dependent β-thalassemia. After previously establishing that lentiviral transfer of a marked β-globin (βA-T87Q) gene could substitute for long-term red-cell transfusions in a patient with β-thalassemia, we wanted to evaluate the safety and efficacy of such gene therapy in patients with transfusion-dependent β-thalassemia.
In two phase 1–2 studies, we obtained mobilized autologous CD34+ cells from 22 patients (12 to 35 years of age) with transfusion-dependent β-thalassemia and transduced the cells ex vivo with LentiGlobin BB305 vector, which encodes adult hemoglobin (HbA) with a T87Q amino acid substitution (HbAT87Q). The cells were then reinfused after the patients had undergone myeloablative busulfan conditioning. We subsequently monitored adverse events, vector integration, and levels of replication-competent lentivirus. Efficacy assessments included levels of total hemoglobin and HbAT87Q, transfusion requirements, and average vector copy number.
At a median of 26 months (range, 15 to 42) after infusion of the gene-modified cells, all but 1 of the 13 patients who had a non–β0/β0 genotype had stopped receiving red-cell transfusions; the levels of HbAT87Q ranged from 3.4 to 10.0 g per deciliter, and the levels of total hemoglobin ranged from 8.2 to 13.7 g per deciliter. Correction of biologic markers of dyserythropoiesis was achieved in evaluated patients with hemoglobin levels near normal ranges. In 9 patients with a β0/β0 genotype or two copies of the IVS1-110 mutation, the median annualized transfusion volume was decreased by 73%, and red-cell transfusions were discontinued in 3 patients. Treatment-related adverse events were typical of those associated with autologous stem-cell transplantation. No clonal dominance related to vector integration was observed.
Gene therapy with autologous CD34+ cells transduced with the BB305 vector reduced or eliminated the need for long-term red-cell transfusions in 22 patients with severe β-thalassemia without serious adverse events related to the drug product. (Funded by Bluebird Bio and others; HGB-204 and HGB-205 ClinicalTrials.gov numbers, NCT01745120 and NCT02151526.)
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