title: Efficacy and Safety of a Preemptive Antiviral Therapy Strategy Based on Combined Virological and Immunological Monitoring for Active Cytomegalovirus Infection in Allogeneic Stem Cell Transplant Recipients.
abstract: Background.  Preemptive antiviral therapy for active cytomegalovirus (CMV) infection in allogeneic stem cell transplant recipients (Allo-SCT) results in overtreatment and a high rate of recurrences. Monitoring of CMV-specific T-cell immunity may help to individualize treatments and minimize these problems. Methods.  We conducted a prospective, multicenter, matched comparison-group study to evaluate the efficacy and safety of a novel strategy that consisted of interrupting anti-CMV therapy upon CMV DNAemia clearance and concurrent detection of phosphoprotein 65/immediate-early-1-specific interferon-γ-producing CD8(+) T cells at levels of >1 cell/µL (within 30 days after the initiation of therapy). Immunological monitoring was performed on days +7, +14, +21, and +28 after treatment initiation. The primary endpoint was the cumulative incidence of recurrent DNAemia within 2 months after treatment cessation. Secondary endpoints were the length of antiviral treatment courses and the incidence of hematological toxicity. Results.  Sixty-one patients were enrolled in the study group. Fifty-six patients were included in the matched-control group. Eleven patients (18%) fulfilled the criteria for antiviral treatment interruption. The cumulative incidence of recurrent CMV DNAemia was significantly lower (P = .02) in these patients than in patients in the comparative groups. Likewise, the length of antiviral treatment courses was significantly shorter in these patients than that in patients in the matched-control group (P = .003). No significant differences in the incidence of hematological toxicity was observed between the comparative groups. Conclusions.  Our data support the clinical utility of combining immunological and virological monitoring for the management of CMV infection in a subset of Allo-SCT recipients.
authors.affiliation: Microbiology Service; Departments of Microbiology.
authors.forename: David
authors.initials: D
authors.lastname: Navarro
authors.affiliation: Hematology and Medical Oncology Service, Hospital Clínico Universitario , Instituto de Investigación INCLIVA , Valencia.
authors.forename: Paula
authors.initials: P
authors.lastname: Amat
authors.affiliation: Hematology Service , Hospital de la Princesa , Madrid.
authors.forename: Rafael
authors.initials: R
authors.lastname: de la Cámara
authors.affiliation: Hematology Service , Hospital Ramón y Cajal , Madrid.
authors.forename: Javier
authors.initials: J
authors.lastname: López
authors.affiliation: Hematoogy Service , Hospital General Universitario , Salamanca.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Vázquez
authors.affiliation: Hematology Unit , Hospital Morales Meseguer , Murcia.
authors.forename: David
authors.initials: D
authors.lastname: Serrano
authors.affiliation: Hematology Unit , Hospital Morales Meseguer , Murcia.
authors.forename: José
authors.initials: J
authors.lastname: Nieto
authors.affiliation: Hematology Unit , Hospital Clinic , Barcelona , Spain.
authors.forename: Monserrat
authors.initials: M
authors.lastname: Rovira
authors.affiliation: Hematology and Medical Oncology Service, Hospital Clínico Universitario , Instituto de Investigación INCLIVA , Valencia.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Piñana
authors.affiliation: Microbiology Service.
authors.forename: Estela
authors.initials: E
authors.lastname: Giménez
authors.affiliation: Hematology and Medical Oncology Service, Hospital Clínico Universitario, Instituto de Investigación INCLIVA, Valencia; Medicine, School of Medicine, University of Valencia.
authors.forename: Carlos
authors.initials: C
authors.lastname: Solano
keywords: IFN-γ CD8+ T cells; allogeneic stem cell transplantation; cytomegalovirus; immunological monitoring; preemptive antiviral therapy