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The New England Journal of Medicine Jun 2023In patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT), a calcineurin inhibitor plus methotrexate has been a standard prophylaxis against... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
In patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT), a calcineurin inhibitor plus methotrexate has been a standard prophylaxis against graft-versus-host disease (GVHD). A phase 2 study indicated the potential superiority of a post-transplantation regimen of cyclophosphamide, tacrolimus, and mycophenolate mofetil.
METHODS
In a phase 3 trial, we randomly assigned adults with hematologic cancers in a 1:1 ratio to receive cyclophosphamide-tacrolimus-mycophenolate mofetil (experimental prophylaxis) or tacrolimus-methotrexate (standard prophylaxis). The patients underwent HSCT from an HLA-matched related donor or a matched or 7/8 mismatched (i.e., mismatched at only one of the , , , and loci) unrelated donor, after reduced-intensity conditioning. The primary end point was GVHD-free, relapse-free survival at 1 year, assessed in a time-to-event analysis, with events defined as grade III or IV acute GVHD, chronic GVHD warranting systemic immunosuppression, disease relapse or progression, and death from any cause.
RESULTS
In a multivariate Cox regression analysis, GVHD-free, relapse-free survival was significantly more common among the 214 patients in the experimental-prophylaxis group than among the 217 patients in the standard-prophylaxis group (hazard ratio for grade III or IV acute GVHD, chronic GVHD, disease relapse or progression, or death, 0.64; 95% confidence interval [CI], 0.49 to 0.83; P = 0.001). At 1 year, the adjusted GVHD-free, relapse-free survival was 52.7% (95% CI, 45.8 to 59.2) with experimental prophylaxis and 34.9% (95% CI, 28.6 to 41.3) with standard prophylaxis. Patients in the experimental-prophylaxis group appeared to have less severe acute or chronic GVHD and a higher incidence of immunosuppression-free survival at 1 year. Overall and disease-free survival, relapse, transplantation-related death, and engraftment did not differ substantially between the groups.
CONCLUSIONS
Among patients undergoing allogeneic HLA-matched HSCT with reduced-intensity conditioning, GVHD-free, relapse-free survival at 1 year was significantly more common among those who received cyclophosphamide-tacrolimus-mycophenolate mofetil than among those who received tacrolimus-methotrexate. (Funded by the National Heart, Lung, and Blood Institute and others; BMT CTN 1703 ClinicalTrials.gov number, NCT03959241.).
Topics: Adult; Humans; Bronchiolitis Obliterans Syndrome; Cyclophosphamide; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Methotrexate; Mycophenolic Acid; Neoplasm Recurrence, Local; Tacrolimus; Unrelated Donors; Hematologic Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37342922
DOI: 10.1056/NEJMoa2215943 -
Journal of Pediatric Intensive Care Jun 2023Acute viral bronchiolitis (AVB) is the leading cause of hospital admissions among infants in developed and developing countries and associated with increased morbidity... (Review)
Review
Acute viral bronchiolitis (AVB) is the leading cause of hospital admissions among infants in developed and developing countries and associated with increased morbidity and cost of treatment. This review was performed to guide the clinicians managing AVB in light of evidence accumulated in the last decade. We searched published English literature in last decade regarding etiology, diagnosis, treatment, and prevention of AVB using PubMed and Cochrane Database of Systematic Reviews. Respiratory syncytial virus is the most common causative agent. The diagnosis is mainly clinical with limited role of diagnostic investigations and chest radiographs are not routinely indicated. The management of AVB remains a challenge, as the role of various interventions is not clear. Supportive care in form of provision of heated and humidified oxygen and maintaining hydration are main interventions. The use of pulse oximetry helps to guide the administration of oxygen. Trials and systematic reviews evaluated various interventions like nebulized adrenaline, bronchodilators and hypertonic saline, corticosteroids, different modes of noninvasive ventilation (high-flow nasal cannula [HFNC], continuous positive airway pressure [CPAP], and noninvasive positive pressure ventilation [NPPV]), surfactant, heliox, chest physiotherapy, and antiviral drugs. The interventions which showed some benefits in infants and children with AVB are adrenaline and hypertonic saline nebulization, HFNC, CPAP, NIV, and surfactant. The routine administration of antibiotics, bronchodilators, corticosteroids, steam inhalation, chest physiotherapy, heliox, and antiviral drugs are not recommended.
PubMed: 37082471
DOI: 10.1055/s-0040-1715852 -
Anales de Pediatria Oct 2023Nirsevimab, a monoclonal antibody for the prevention of disease caused by respiratory syncytial virus (RSV), has recently been approved for use in Europe and Spain. (Review)
Review
INTRODUCTION
Nirsevimab, a monoclonal antibody for the prevention of disease caused by respiratory syncytial virus (RSV), has recently been approved for use in Europe and Spain.
OBJECTIVES
To provide recommendations for the administration of nirsevimab for prevention of RSV disease.
METHODS
The approach chosen to develop these recommendations involved a critical review of the literature and the use of the Delphi and GRADE methods. An expert group was formed. The group engaged in three rounds to define the questions, express support or opposition, grade recommendations and establish the agreement or disagreement with the conclusions.
RESULTS
In the general neonatal population, routine administration of nirsevimab is recommended to reduce the frequency of illness and hospitalisation for bronchiolitis and RSV lower respiratory tract infection. Nirsevimab is recommended for all infants born in high-incidence RSV season and infants aged less than 6 months at the season onset. In infants born preterm between 29 and 35 weeks of gestation, with haemodynamically significant heart disease or with chronic lung disease, routine administration of nirsevimab is recommended to reduce the incidence of disease and hospitalisation due to bronchiolitis and RSV lower respiratory tract infection. In patients in whom palivizumab is currently indicated, its substitution by nirsevimab is recommended to reduce the burden of bronchiolitis.
CONCLUSIONS
Routine administration of nirsevimab to all infants aged less than 6 months born during the RSV season or aged less than 6 months at the start of the winter season is recommended to reduce the burden of disease and the frequency of hospitalization due to bronchiolitis.
Topics: Infant, Newborn; Infant; Humans; Child; Antiviral Agents; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Communicable Diseases; Respiratory Tract Infections; Bronchiolitis
PubMed: 37743207
DOI: 10.1016/j.anpede.2023.09.006