Antiviral prophylaxis in haematological patients: Systematic review and meta-analysis |
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| Authors: | Dafna Yahav Anat Gafter-Gvili Eli Muchtar Keren Skalsky Galia Kariv Moshe Yeshurun Leonard Leibovici Mical Paul |
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| Affiliation: | 1. Department of Medicine E, Rabin Medical Center, Beilinson Hospital, Sackler Faculty of Medicine, Tel-Aviv University, Israel;2. Department of Haemato-oncology and Bone Marrow Transplantation, Rabin Medical Center, Beilinson Hospital, Sackler Faculty of Medicine, Tel-Aviv University, Israel;3. Unit of Infectious Diseases, Rabin Medical Center, Beilinson Hospital, Sackler Faculty of Medicine, Tel-Aviv University, Israel;1. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA;2. Department of Medicine, University of Washington, Seattle, WA, USA;3. Department of Biostatistics, University of Washington, Seattle, WA, USA;4. Department of Laboratory Medicine, University of Washington, Seattle, WA, USA;5. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA;6. Department of Pharmacoepidemiology, Merck and Co Inc, Kenilworth, NJ, USA;1. Department of Internal Medicine, University of Kentucky, Lexington, KY, United States;2. Division of Hematology and Medical Oncology, Mayo Clinic, Phoenix, AZ, United States;3. Division of Hematology and Blood and Marrow Transplant, University of Kentucky Markey Cancer Center, Lexington, KY, United States;4. Biostatistics Shared Resource Facility, University of Kentucky Markey Cancer Center, Lexington, KY, United States;5. Division of Hematology, University of Cincinnati Cancer Center, Cincinnati, OH, United States;1. Haematology Department, Henri Mondor Hospital, Assistance Publique-Hopitaux de Paris, Créteil, France;2. University Paris-Est Créteil, Créteil, France;3. Section of Hematology, Department of Medicine, Sahlgrenska University Hospital, Sahlgrenska Academy, Göteborg, Sweden;4. Pediatric Hematology Oncology Unit, Department of Mother and Child, Azienda Ospedaliera Universitaria Integrata, Verona, Italy;5. University of Genoa (DISSAL) and IRCCS Ospedale Policlinico San Martino, Genova, Italy;6. Department of Hematology Oncology, University of Munich, Germering, Germany;7. Department of Haematological Medicine, King''s College Hospital NHS Foundation Trust, London, UK;8. Paediatric Haematology and Oncology Department, Hospital for Children and Adolescents, University of Frankfurt, Frankfurt, Germany;9. Department of Pediatrics, Hadassah-Hebrew University Medical Center, Ein-Kerem Jerusalem, Israel;10. Department of Cellular Therapy and Allogeneneic Stem Cell Transplantation, Karolinska University Hospital, Stockholm, Sweden;11. Karolinska Institutet, Stockholm, Sweden;1. GSK, Rockville, MD, USA;2. Department of Hematology, Ankara University Medicine Faculty, Ankara, Turkey;3. Department of Hemato-Oncology, Internal Medicine, Inje University Busan Paik Hospital, Busan, South Korea;4. Department of Haematology, University of Opole, Provincial Hospital, Opole, Poland;5. Department of Internal Medicine, Chonbuk National University Medical School and Hospital, Jeonju, South Korea;6. Department of Haematological Medicine, King''s College Hospital, London, UK;7. Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea;8. Department of Hematology, Gregorio Marañon University Hospital, Madrid, Spain;9. Division of Transfusion Medicine, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan;10. Complejo Hospitalario Metropolitano Dr Arnulfo Arias Madrid, Panama City, Panama;11. Infectious Diseases Department, Institut Jules Bordet, Brussels, Belgium;12. Department of Hematology, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain;13. Hematology Department, Hospital Universitario 12 de Octubre, Madrid, Spain;14. Department of Haematology, The Kinghorn Cancer Centre, St Vincents Hospital, Darlinghurst, NSW, Australia;15. Department of Haematology, University Hospital Monklands, NHS Lanarkshire, Airdrie, Scotland, UK;p. Canadian Center for Vaccinology, IWK Health Centre and Nova Scotia Health Authority, Dalhousie University, Halifax, NS, Canada;q. GSK, Rixensart, Belgium;r. GSK, Wavre, Belgium;s. Halozyme Therapeutics, San Diego, CA, USA;t. CureVac, Tübingen, Germany;1. Department of Virology I, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo, 162-8640, Japan;2. Department of Pediatrics, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan;3. Department of Hematology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan;4. Virus Research Center, Sendai Medical Center, 2-8-8 Miyagino, Miyagino-ku, Sendai-shi, Miyagi, 983-8520, Japan;5. Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo, Japan |
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| Abstract: | PurposeAntiviral prophylaxis is commonly prescribed to haematological cancer patients. We conducted a systematic review and meta-analysis to quantify its overall benefit in specific clinical scenarios.MethodsRandomised controlled trials assessing antiviral prophylaxis versus placebo, no treatment, pre-emptive treatment or another antiviral drug were included. Patients undergoing haematopoietic stem cell transplantation (HSCT) or intensive chemotherapy for acute leukaemia or high-grade lymphoma were included. No restrictions on language, year or publication status were applied. Overall mortality, herpes simplex virus (HSV) and cytomegalovirus (CMV) diseases were assessed as primary outcomes. Pooled relative risks (RRs) and numbers needed to treat (NNT) with 95% confidence intervals (CI) are reported.ResultsHSCT was the condition assessed in 22 trials and intensive chemotherapy in 5 trials. In the pre-engraftment setting of autologous or allogeneic HSCT, antiviral prophylaxis (mainly acyclovir for HSV seropositive recipients) significantly reduced HSV (NNT 2, 2–2, control event rate (CER) 61.9%) and CMV disease, with no effect on overall mortality. In the allogeneic post-engraftment setting (mainly CMV-seropositive recipients/donors), antiviral prophylaxis resulted in a significant reduction in overall mortality, RR 0.79 (0.65–0.95), NNT 12 (7–50, CER 39.4%) and all viral-related outcomes. In this setting, acyclovir significantly reduced overall mortality (RR 0.71, 0.53–0.96, 4 trials) and ganciclovir/maribavir significantly reduced CMV disease (RR 0.26, 0.14–0.48, 5 trials). During chemotherapy, acyclovir significantly decreased HSV disease (NNT 3, 2–4, CER 37.4%) and infection rates, with no effect on mortality.ConclusionsAntiviral prophylaxis reduced mortality with a small NNT in the post-engraftment setting of allogeneic HSCT. In the pre-engraftment phase and during chemotherapy only viral-related morbidity was reduced. |
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