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      Guidelines from the 2017 European Conference on Infections in Leukaemia for management of HHV-6 infection in patients with hematologic malignancies and after hematopoietic stem cell transplantation

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          Abstract

          Of the two human herpesvirus 6 (HHV-6) species, human herpesvirus 6B (HHV-6B) encephalitis is an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplant. Guidelines for the management of HHV-6 infections in patients with hematologic malignancies or post-transplant were prepared a decade ago but there have been no other guidelines since then despite significant advances in the understanding of HHV-6 encephalitis, its therapy, and other aspects of HHV-6 disease in this patient population. Revised guidelines prepared at the 2017 European Conference on Infections in Leukaemia covering diagnosis, preventative strategies and management of HHV-6 disease are now presented.

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          Chromosomally integrated human herpesvirus 6: questions and answers

          Philip E Pellett, Dharam V Ablashi, Peter Ambros … (2011)
          SUMMARY Chromosomally integrated human herpesvirus 6 (ciHHV-6) is a condition in which the complete HHV-6 genome is integrated into the host germ line genome and is vertically transmitted in a Mendelian manner. The condition is found in less than 1% of controls in the USA and UK, but has been found at a somewhat higher prevalence in transplant recipients and other patient populations in several small studies. HHV-6 levels in whole blood that exceed 5.5 log10 copies/ml are strongly suggestive of ciHHV-6. Monitoring DNA load in plasma and serum is unreliable, both for identifying and for monitoring subjects with ciHHV-6 due to cell lysis and release of cellular DNA. High HHV-6 DNA loads associated with ciHHV-6 can lead to erroneous diagnosis of active infection. Transplant recipients with ciHHV-6 may be at increased risk for bacterial infection and graft rejection. ciHHV-6 can be induced to a state of active viral replication in vitro. It is not known whether ciHHV-6 individuals are put at clinical risk by the use of drugs that have been associated with HHV-6 reactivation in vivo or in vitro. Nonetheless, we urge careful observation when use of such drugs is indicated in individuals known to have ciHHV-6. Little is known about whether individuals with ciHHV-6 develop immune tolerance for viral proteins. Further research is needed to determine the role of ciHHV-6 in disease. Copyright © 2011 John Wiley & Sons, Ltd.
          Article 0 comments Cited 100 times – based on 0 reviews     Review now
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            Management of CMV, HHV-6, HHV-7 and Kaposi-sarcoma herpesvirus (HHV-8) infections in patients with hematological malignancies and after SCT.

            P Reusser, H. Einsele, Ricardo Jacó de Oliveira … (2008)
            These recommendations were prepared by the European Conference on Infections in Leukaemia following a predefined methodology. Literature searches were made to identify studies pertinent to management of CMV, HHV-6, -7 and -8 infections. For CMV, 76 studies were reviewed: 72 published and 4 presented as abstracts. Twenty-nine of these studies were prospective randomized trials. For the other herpesviruses, HHV-6, -7 and -8, no randomized controlled trial has been performed, although data from some studies with other primary endpoints have been used to assess the management of HHV-6 infection. Works presented only as abstracts were used to a very limited extent. The quality of evidence and level of recommendation were graded according to the Center for Disease Control (CDC) criteria.
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              Idiopathic pneumonia syndrome after hematopoietic cell transplantation: evidence of occult infectious etiologies

              C. Renaud, S. Seo, J M Kuypers … (2015)
              Newer diagnostic methods may link more idiopathic pneumonia syndrome (IPS) cases to an infectious agent. Bronchoalveolar lavage (BAL) samples from 69 hematopoietic cell transplant (HCT) recipients with IPS diagnosed between 1992 and 2006 were tested for 28 pathogens (3 bacteria and 25 viruses) by quantitative polymerase chain reaction and for Aspergillus by galactomannan assay. Research BALs from 21 asymptomatic HCT patients served as controls. Among 69 HCT patients with IPS, 39 (56.5%) had a pathogen detected. The most frequent pathogens were human herpesvirus-6 (HHV-6) (N = 20 [29%]) followed by human rhinovirus (HRV), cytomegalovirus (CMV), and Aspergillus (N = 8 [12%] in each). HHV-6 and HRV were rarely detected in controls, whereas CMV and Aspergillus were occasionally detected with low pathogen load. Patients with pathogens had worse day-100 survival than those without (hazard ratio, 1.88; P = .03). Mortality in patients with only pathogens of "uncertain" significance in lung was similar to that in patients with pathogens of "established" significance. Metagenomic next-generation sequencing did not reveal additional significant pathogens. Our study demonstrated that approximately half of patients with IPS had pathogens detected in BAL, and pathogen detection was associated with increased mortality. Thus, an expanded infection detection panel can significantly increase the diagnostic precision for idiopathic pneumonia.
              Article 0 comments Cited 68 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Per Ljungman: On behalf of : for the 2017 European Conference on Infections in Leukaemia (ECIL)
                Journal
                Journal ID (nlm-ta): Haematologica
                Journal ID (iso-abbrev): Haematologica
                Journal ID (hwp): haematol
                Journal ID (publisher-id): Haematologica
                Title: Haematologica
                Publisher: Ferrata Storti Foundation
                ISSN (Print): 0390-6078
                ISSN (Electronic): 1592-8721
                Publication date (Print): November 2019
                Publication date (Electronic preprint): 29 August 2019
                Volume: 104
                Issue: 11
                Pages: 2155-2163
                Affiliations
                [1 ]Division of Infection and Immunity, University College London, London, UK
                [2 ]Fred Hutchinson Cancer Research Center, Seattle, WA, USA
                [3 ]Department of Medical Microbiology and Department of Paediatric Haematology and Oncology 2 nd Medical Faculty of Charles University and Motol University Hospital, Prague, Czech Republic
                [4 ]Department of Haematology, Hospital de la Princesa, Madrid, Spain
                [5 ]SIMT, ASST di Bergamo Ovest, Treviglio, Italy
                [6 ]Medizinische Klinik und Poliklinik II, Julius Maximilians Universität, Würzburg, Germany
                [7 ]Microbiology Service, Hospital Clínico Universitario, Instituto de Investigación INCLIVA and Department of Microbiology, School of Medicine, University of Valencia, Valencia, Spain
                [8 ]Department of Haematology, Henri Mondor Hospital, Assistance Publique-Hopitaux de Paris, Université Paris-Est Créteil, Créteil, France
                [9 ]Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Division of Haematology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
                Author notes
                Correspondence: KATHERINE N WARD k.n.ward@ 123456ucl.ac.uk
                Article
                Publisher ID: 1042155
                DOI: 10.3324/haematol.2019.223073
                PMC ID: 6821622
                PubMed ID: 31467131
                SO-VID: 3a54012e-e408-453d-8c3d-432288b417cb
                Copyright © Copyright© 2019 Ferrata Storti Foundation
                License:

                Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions:

                https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions:

                https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher.

                History
                Date received : 01 April 2019
                Date accepted : 27 August 2019
                Categories
                Subject: Guideline Article

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