Effect of Recombinant Zoster Vaccine on Incidence of Herpes Zoster After Autologous Stem Cell Transplantation: A Randomized Clinical Trial.

Importance: Herpes zoster, a frequent complication following autologous hematopoietic stem cell transplantation (HSCT), is associated with significant morbidity. A nonlive adjuvanted recombinant zoster vaccine has been developed to prevent posttransplantation zoster. Objective: To assess the efficacy and adverse event profile of the recombinant zoster vaccine in immunocompromised autologous HSCT recipients. Design, Setting, and Participants: Phase 3, randomized, observer-blinded study conducted in 167 centers in 28 countries between July 13, 2012, and February 1, 2017, among 1846 patients aged 18 years or older who had undergone recent autologous HSCT. Interventions: Participants were randomized to receive 2 doses of either recombinant zoster vaccine (n = 922) or placebo (n = 924) administered into the deltoid muscle; the first dose was given 50 to 70 days after transplantation and the second dose 1 to 2 months thereafter. Main Outcomes and Measures: The primary end point was occurrence of confirmed herpes zoster cases. Results: Among 1846 autologous HSCT recipients (mean age, 55 years; 688 [37%] women) who received 1 vaccine or placebo dose, 1735 (94%) received a second dose and 1366 (74%) completed the study. During the 21-month median follow-up, at least 1 herpes zoster episode was confirmed in 49 vaccine and 135 placebo recipients (incidence, 30 and 94 per 1000 person-years, respectively), an incidence rate ratio (IRR) of 0.32 (95% CI, 0.22-0.44; P < .001), equivalent to 68.2% vaccine efficacy. Of 8 secondary end points, 3 showed significant reductions in incidence of postherpetic neuralgia (vaccine, n=1; placebo, n=9; IRR, 0.1; 95% CI, 0.00-0.78; P = .02) and of other prespecified herpes zoster-related complications (vaccine, n=3; placebo, n=13; IRR, 0.22; 95% CI, 0.04-0.81; P = .02) and in duration of severe worst herpes zoster-associated pain (vaccine, 892.0 days; placebo, 6275.0 days; hazard ratio, 0.62; 95% CI, 0.42-0.89; P = .01). Five secondary objectives were descriptive. Injection site reactions were recorded in 86% of vaccine and 10% of placebo recipients, of which pain was the most common, occurring in 84% of vaccine recipients (grade 3: 11%). Unsolicited and serious adverse events, potentially immune-mediated diseases, and underlying disease relapses were similar between groups at all time points. Conclusions and Relevance: Among adults who had undergone autologous HSCT, a 2-dose course of recombinant zoster vaccine compared with placebo significantly reduced the incidence of herpes zoster over a median follow-up of 21 months. Trial Registration: ClinicalTrials.gov Identifier: NCT01610414.

[Bacteraemia and infection of the vascular catheter in the haematology patient: positioning and management based on the Delphi method]. / Bacteriemia e infección del catéter vascular en el ámbito hematológico: posicionamiento y actitudes de manejo basados en el método Delphi.

OBJECTIVE: Infectious complications are an important cause of morbidity and mortality in haematological patients with febrile neutropenia. The aim of this study was to develop a consensus document of recommendations to optimize the management of febrile neutropenic patients with haematological or vascular catheter infections in areas where there is no solid scientific evidence. METHODS: After reviewing the scientific evidence, a scientific committee composed of experts in haematology and infectious diseases developed a survey with 55 statements. A two- round modified Delphi method was used to achieve consensus. RESULTS: The online survey was answered by 52 experts in the field of haematology and infectious diseases. After two rounds of evaluation, a consensus was possible in 43 of the 55 statements (78.2%): 40 in agreement and 3 in disagreement. Recommendations are given related to empirical antibiotic treatment of patients with febrile neutropenia, mechanisms of action, toxicity and synergism of antibiotics in this context, modifications of antibiotic treatment in the course of febrile neutropenia, and the management of central vascular catheter infections in the haematological setting. CONCLUSIONS: There is a high degree of agreement among experts on some controversial issues concerning the management of febrile neutropenia and catheter infection in hematologic patients. This agreement has resulted in recommendations that may be useful in clinical practice.

Bacteriemia e infección del catéter vascular en el ámbito hematológico: posicionamiento y actitudes de manejo basados en el método Delphi / Bacteraemia and infection of the vascular catheter in the haematology patient: positioning and management based on the Delphi method

Introducción. Las complicaciones infecciosas son una causa importante de morbi-mortalidad en los pacientes hematológicos con neutropenia febril. El objetivo del presente trabajo fue desarrollar un documento de recomendaciones consensuado para optimizar el manejo del paciente hematológico con neutropenia febril o infecciones por catéteres vasculares en áreas en las que no se dispone de una sólida evidencia científica. Material y métodos. Tras la revisión de las evidencias científico-médicas, un comité científico formado por especialistas expertos en hematología y enfermedades infecciosas elaboró una encuesta con 55 aseveraciones. Para el consenso se utilizó un método Delphi modificado con dos rondas de evaluación. Resultados. La encuesta fue respondida online por 52 especialistas en hematología y en enfermedades infecciosas. Tras las dos rondas de evaluación fue posible el consenso en 43 de los 55 ítems planteados (un 78,2%): 40 en el acuerdo y 3 en el desacuerdo. Con ello, se proporcionan una serie de recomendaciones relativas al tratamiento antibiótico empírico del paciente con neutropenia febril, a cuestiones relacionadas con mecanismos de acción, toxicidad y sinergia de los antibióticos en este contexto, a las modificaciones del tratamiento antibiótico en el curso de la neutropenia febril y al manejo de las infecciones de catéter vascular central en el ámbito hematológico. Conclusiones. Existe un alto grado de acuerdo entre los expertos consultados sobre algunos aspectos controvertidos relativos al manejo de la neutropenia febril y la infección por catéter en pacientes hematológicos. Este acuerdo se ha traducido en unas recomendaciones que pueden ser de utilidad en la práctica clínica (AU)

Introduction. Infectious complications are an important cause of morbidity and mortality in haematological patients with febrile neutropenia. The aim of this study was to develop a consensus document of recommendations to optimize the management of febrile neutropenic patients with haematological or vascular catheter infections in areas where there is no solid scientific evidence. Materials and Methods. After reviewing the scientific evidence, a scientific committee composed of experts in haematology and infectious diseases developed a survey with 55 statements. A two- round modified Delphi method was used to achieve consensus. Results. The online survey was answered by 52 experts in the field of haematology and infectious diseases. After two rounds of evaluation, a consensus was possible in 43 of the 55 statements (78.2%): 40 in agreement and 3 in disagreement. Recommendations are given related to empirical antibiotic treatment of patients with febrile neutropenia, mechanisms of action, toxicity and synergism of antibiotics in this context, modifications of antibiotic treatment in the course of febrile neutropenia, and the management of central vascular catheter infections in the haematological setting. Conclusions. There is a high degree of agreement among experts on some controversial issues concerning the management of febrile neutropenia and catheter infection in hematologic patients. This agreement has resulted in recommendations that may be useful in clinical practice (AU)