Reporting of the epidemiology and outcomes including CMV infection and disease rates with current preventative strategies and delineation of the short and long-term indirect effects of CMV in pediatric transplant recipients is encouraged. Further, additional investigation into the diagnostic and predictive utility of immunogenetic biomarkers and adjunctive immunologic monitoring to guide preventative and treatment strategies should be explored. Investigation into optimal CMV prevention strategies should include appreciation for impact on different age groups and potential consequences of antiviral side effects in pediatric-aged patients. Finally, pediatric data should be obtained for emerging antiviral agents to expand the opportunities to prevent and treat CMV.
Numerous updates have been added to these guidelines. In the diagnostics field, the advent of an international standard for CMV viral load testing and reporting of values in IU/mL will eventually allow for harmonization of viral load tests with subsequent development of thresholds for preemptive and diagnostic protocols. QNAT is increasingly used and preferred for diagnosis, decisions regarding preemptive therapy, and monitoring response to therapy. There is substantially more evidence to support the use of immunodiagnostics as an adjunct tool to predict the risk of CMV disease. Vaccine development continues and holds increasing promise as a future prevention strategy. Updates in the prevention field include the effectiveness of prolonging prophylaxis in D+/R- kidney recipients from 100 to 200 days and from 3 to 12 months in lung transplant recipients. Trials with carefully executed preemptive therapy, using low viral load thresholds, demonstrate similar outcomes to universal prophylaxis including similar long-term graft survival. Some experts are using a hybrid approach (prophylaxis followed by preemptive therapy) with increased frequency. Valganciclovir is increasingly used as the preferred agent for treatment (except for life-threatening cases and situations with questionable drug bioavailability or noncompliance). Additional specific recommendations on the use of IVIG with CMV treatment are included. Differences between different algorithms for determining estimated glomerular filtration rate and the risk of overdosing have been highlighted. Diagnostic resistance mutations have been updated and the clinical management algorithm for ganciclovir-resistant CMV has been slightly modified to clarify decision-making criteria. Alternative therapy has been updated to reflect current experimental drugs. In the pediatrics section, valganciclovir is included in the prevention and treatment of CMV due to new data detailing the pharmacokinetics of valganciclovir in pediatrics. Prophylaxis, preemptive therapy, and hybrid regimens are all now recommended regimens for CMV prevention in children, as emerging data support each of these strategies, albeit without comparative efficacy studies.
The authors thank Frank Lindo Verissimo, Danielle Viau, and Catherin Parker of The Transplantation Society for their administrative support and Dr. Michael Boeckh for detailed review. These guidelines are dedicated in memory of Dr. Mark D. Pescovitz (1955–2010), a participant in the last set of guidelines and major contributor to the field of organ transplantation and specifically CMV. The authors miss him dearly.
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APPENDIX 1 Consensus Contributors (in alphabetical order)
Leaders: Camille N. Kotton (USA) and Atul Humar (Canada)
Diagnostics: Angela M. Caliendo (leader, USA), Irmeli Lautenschlager (Finland), Jutta Preiksaitis (Canada)
Immunology: Deepali Kumar (leader, Canada), Davide Abate (Italy), Vincent Emery (United Kingdom), Rajiv Khanna (Australia), Daniele Lilleri (Italy), Oriol Manuel (Switzerland), Martina Sester (Germany)
Prevention: Atul Humar (coleader, Canada) and Camille N. Kotton (coleader, USA), Emily Blumberg (USA), Luis F.A. Camargo (Brazil), Chad Gordon (USA), Shirish Huprikar (USA), Nassim Kamar (France), Roberta Lattes (Argentina), Pierre Merville (France), Nicolas Mueller (Switzerland), Graham Paget (South Africa), Tomas Reischig (Czech Republic), Nina Singh (USA), David R. Snydman (USA), Julian Torre-Cisneros (Spain), Glen Westall (Australia), Martin Zamora (USA)
Treatment: Anders Åsberg (leader, Norway), Jennifer Harrison (Canada), Michele Morris (USA), Patricia Munoz (Spain), William Rawlinson (Australia)
Resistance: Sunwen Chou (leader, USA), Sophie Alain (France), Fausto Baldanti (Italy), Ajit P. Limaye (USA), Nell Lurain (USA)
Pediatrics: Lara Danziger-Isakov (leader, USA), Upton Allen (Canada), Michael Green (USA), Betsy C. Herold (USA), Marian Michaels (USA)