UPDATE ON CYTOMEGALOVIRUS INFECTION MANAGEMENT IN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANT RECIPIENTS A Consensus Document of the Spanish Group for Hematopoietic Transplantation and Cell Therapy (GETH-TC)

Main Article Content

José Luis Piñana
Estela Giménez
Lourdes Vázquez
María Ángeles Marcos
Manuel Guerreiro
Rafael Duarte
Ariadna Pérez
Carlos de Miguel
Ildefonso Espigado
Marta González-Vicent
María Suarez-Lledó
Irene García-Cadenas
Rodrigo Martino
Angel Cedillo
Monserrat Rovira
Rafael de la Cámara
David Navarro
Carlos Solano https://orcid.org/0000-0003-3702-0817

Keywords

Cytomegalovirus, CMV monitoring, antiviral prophylaxis, preemptive antiviral therapy, CMV DNA doubling time, CMV-specific T-cell immunity, clinically significant CMV infection

Abstract

Background: Cytomegalovirus (CMV) infection is a common complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and in patients receiving novel hematological therapies. Its impact on morbidity and mortality necessitates effective management strategies. Despite recent advances in diagnostics and treatment, unresolved questions persist regarding monitoring and treatment, prompting the need for updated recommendations.


Methods: A consensus was reached among a panel of experts selected for their expertise in CMV research and clinical practice. Key clinical areas and questions were identified based on previous surveys and literature reviews. Recommendations were formulated through consensus and graded using established guidelines.


Results: Recommendations were provided for virological monitoring, including the timing and frequency of CMV DNAemia surveillance, especially during letermovir (LMV) prophylaxis. We evaluated the role of CMV DNA load quantification in diagnosing CMV disease, particularly pneumonia and gastrointestinal involvement, along with the utility of specific CMV immune monitoring in identifying at-risk patients. Strategies for tailoring LMV prophylaxis, managing breakthrough DNAemia, and implementing secondary prophylaxis in refractory cases were outlined. Additionally, criteria for initiating early antiviral treatment based on viral load dynamics were discussed.


Conclusion: The consensus provides updated recommendations for managing CMV infection in hematological patients, focusing on unresolved issues in monitoring, prophylaxis, treatment, and resistance. These recommendations aim to guide clinical practice and improve outcomes in this high-risk population. Further research is warranted to validate these recommendations and address ongoing challenges in CMV management with emerging antiviral combinations, particularly in pediatric populations.

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References

1. Schmidt-Hieber M, Labopin M, Beelen D, et al. CMV serostatus still has an important prognostic impact in de novo acute leukemia patients after allogeneic stem cell transplantation: A report from the Acute Leukemia Working Party of EBMT. Blood. 2013;122(19):3359-3364. doi:10.1182/blood-2013-05-499830
2. Solano de la Asuncion C, Giménez E, Hernández-Boluda JC, et al. Immunobiology of cytomegalovirus infection in patients with haematological malignancies undergoing treatment with small molecule inhibitors. Br J Haematol. 2023;200(6):e58-e61. doi:10.1111/bjh.18655
3. Márquez-Algaba E, Iacoboni G, Pernas B, et al. Impact of Cytomegalovirus Replication in Patients with Aggressive B Cell Lymphoma Treated with Chimeric Antigen Receptor T Cell Therapy. Transplant Cell Ther. 2022;28(12):851.e1-851.e8. doi:10.1016/j.jtct.2022.09.007
4. Chen G, Herr M, Nowak J, et al. Cytomegalovirus reactivation after CD19 CAR T-cell therapy is clinically significant. Haematologica. 2023;108(2):615-620. doi:10.3324/haematol.2022.281719
5. Green ML, Leisenring W, Xie H, et al. Cytomegalovirus viral load and mortality after haemopoietic stem cell transplantation in the era of pre-emptive therapy : a retrospective cohort study. Lancet Haematol. 2016;3026(15):1-9. doi:10.1016/S2352-3026(15)00289-6
6. Einsele H, Ljungman P, Boeckh M. How I treat CMV reactivation after allogeneic hematopoietic stem cell transplantation. Blood. 2020;135(19):1619-1629. doi:10.1182/blood.2019000956
7. Ljungman P, Tridello G, Piñana JL, et al. Improved outcomes over time and higher mortality in CMV seropositive allogeneic stem cell transplantation patients with COVID-19; An infectious disease working party study from the European Society for Blood and Marrow Transplantation registry. Front Immunol. 2023;14(March):1-11. doi:10.3389/fimmu.2023.1125824
8. Boeckh M, Nichols WG. The impact of cytomegalovirus serostatus of donor and recipient before hematopoietic stem cell transplantation in the era of antiviral prophylaxis and preemptive therapy. Blood. 2004;103(6):2003-2008. doi:10.1182/blood-2003-10-3616
9. Cesaro S, Ljungman P, Tridello G, et al. New trends in the management of cytomegalovirus infection after allogeneic hematopoietic cell transplantation: a survey of the Infectiois Diseases Working Pary of EBMT. Bone Marrow Transplant. 2022;(July). doi:10.1038/s41409-022-01863-8
10. Dadwal SS. Update on prevention of cytomegalovirus in hematopoietic cell transplantation. Curr Opin Infect Dis. 2019;32(1):63-68. doi:10.1097/QCO.0000000000000517
11. Ljungman P, de la Camara R, Robin C, et al. Guidelines for the management of cytomegalovirus infection in patients with haematological malignancies and after stem cell transplantation from the 2017 European Conference on Infections in Leukaemia (ECIL 7). Lancet Infect Dis. 2019;19(8):e260-e272. doi:10.1016/S1473-3099(19)30107-0
12. Girmenia C, Lazzarotto T, Bonifazi F, et al. Assessment and prevention of cytomegalovirus infection in allogeneic hematopoietic stem cell transplant and in solid organ transplant: A multidisciplinary consensus conference by the Italian GITMO, SITO, and AMCLI societies. Clin Transplant. 2019;33(10):e13666. doi:10.1111/ctr.13666
13. Hakki M, Aitken SL, Danziger-Isakov L, et al. American Society for Transplantation and Cellular Therapy Series: #3—Prevention of Cytomegalovirus Infection and Disease After Hematopoietic Cell Transplantation. Transplant Cell Ther. 2021;27(9):707-719. doi:10.1016/j.jtct.2021.05.001
14. Yong MK, Shigle TL, Kim YJ, Carpenter PA, Chemaly RF, Papanicolaou GA. American Society for Transplantation and Cellular Therapy Series: #4 - Cytomegalovirus treatment and management of resistant or refractory infections after hematopoietic cell transplantation: ASTCT Guidelines on CMV treatment. Transplant Cell Ther. 2021;27(12):957-967. doi:10.1016/j.jtct.2021.09.010
15. Solano C, de la Camara R, Vazquez L, Lopez J, Gimenez E, Navarro D. Cytomegalovirus Infection Management in Allogeneic Stem Cell Transplant Recipients: a National Survey in Spain. J Clin Microbiol. 2015;53(8):2741-2744. doi:10.1128/JCM.01057-15
16. Solano C, Vazquez L, Gimenez E, et al. Cytomegalvirus DNAemia and risk of mortality in allogeneic hematopoietic stem cell transplantation: Analysis from the Spanish Hematopoietic Transplantation and Cell Therapy Group. Am J Transplant. 2020;Online ahe. doi:10.1111/ajt.16147
17. Ullmann AJ, Cornely OA, Donnelly JP, et al. ESCMID guideline for the diagnosis and management of Candida diseases 2012: Developing European guidelines in clinical microbiology and infectious diseases. Clin Microbiol Infect. 2012;18(SUPPL.7):1-8. doi:10.1111/1469-0691.12037
18. Solano de la Asunción C, Hernani R, Albert E, et al. Cytomegalovirus DNAemia in haematological patients undergoing CD19-directed chimeric antigen receptor T-cell therapy: should it be systematically monitored? Clin Microbiol Infect. 2023;29(8):1093-1095. doi:10.1016/j.cmi.2023.05.010
19. Kampouri E, Little JS, Rejeski K, Manuel O, Hammond SP, Hill JA. Infections after chimeric antigen receptor (CAR)-T-cell therapy for hematologic malignancies. Transpl Infect Dis. 2023;25(S1):1-17. doi:10.1111/tid.14157
20. Rejeski K, Wang Y, Albanyan O, et al. The CAR-HEMATOTOX score identifies patients at high risk for hematological toxicity, infectious complications, and poor treatment outcomes following brexucabtagene autoleucel for relapsed or refractory MCL. Am J Hematol. 2023;98(11):1699-1710. doi:10.1002/ajh.27056
21. Solano de la Asunción C, Terol MJ, Saus A, et al. Cytomegalovirus-specific T-cell immunity and DNAemia in patients with chronic lymphocytic leukaemia undergoing treatment with ibrutinib. Br J Haematol. 2021;195(4):637-641. doi:10.1111/bjh.17732
22. de la Asunción CS, Giménez E, Hernández-Boluda JC, et al. Assessment of the potential value of plasma Torque Teno virus DNA load monitoring to predict cytomegalovirus DNAemia in patients with hematological malignancies treated with small molecule inhibitors: A proof-of-concept study. J Med Virol. 2023;95(7):e28933. doi:10.1002/jmv.28933
23. Cassaniti I, Colombo AA, Bernasconi P, et al. Positive HCMV DNAemia in stem cell recipients undergoing letermovir prophylaxis is expression of abortive infection. Am J Transplant. 2021;21(4):1622-1628. doi:10.1111/ajt.16450
24. Weinberger S, Steininger C. Reliable quantification of Cytomegalovirus DNAemia in Letermovir treated patients. Antiviral Res. 2022;201(January):105299. doi:10.1016/j.antiviral.2022.105299
25. Giménez E, Guerreiro M, Torres I, et al. Features of cytomegalovirus DNAemia and virus‐specific T‐cell responses in allogeneic hematopoietic stem‐cell transplant recipients during prophylaxis with letermovir. Transpl Infect Dis. Published online February 7, 2023. doi:10.1111/tid.14021
26. Solano C, Giménez E, Albert E, Piñana JL, Navarro D. Immunovirology of cytomegalovirus infection in allogeneic stem cell transplant recipients undergoing prophylaxis with letermovir: A narrative review. J Med Virol. 2023;95(8):e29005. doi:10.1002/jmv.29005
27. Boeckh M, Ljungman P. How we treat cytomegalovirus in hematopoietic cell transplant recipients. Blood. 2009;113(23):5711-5719. doi:10.1182/blood-2008-10-143560
28. Sadowska-Klasa A, Leisenring WM, Limaye AP, Boeckh M. Cytomegalovirus Viral Load Threshold to Guide Preemptive Therapy in Hematopoietic Cell Transplant Recipients: Correlation With Cytomegalovirus Disease. J Infect Dis. 2024;229(5):1435-1439. doi:10.1093/infdis/jiad386
29. Giménez E, Torres I, Albert E, et al. Cytomegalovirus ( CMV ) infection and risk of mortality in allogeneic hematopoietic stem cell transplantation (Allo ‐ HSCT ): A systematic review, meta‐analysis, and meta‐regression analysis. Am J Transpl. 2019;19(March):2479-2494. doi:10.1111/ajt.15515
30. Gimenez E, Munoz-Cobo B, Solano C, Amat P, Navarro D. Early kinetics of plasma cytomegalovirus DNA load in allogeneic stem cell transplant recipients in the era of highly sensitive real-time PCR assays: does it have any clinical value? J Clin Microbiol. 2014;52(2):654-656. doi:10.1128/JCM.02571-13
31. Solano C, Gimenez E, Pinana JL, et al. Preemptive antiviral therapy for CMV infection in allogeneic stem cell transplant recipients guided by the viral doubling time in the blood. Bone Marrow Transplant. 2016;51(5):718-721. doi:10.1038/bmt.2015.303
32. Vinuesa V, Gimenez E, Solano C, Gimeno C, Navarro D. Would Kinetic Analyses of Plasma Cytomegalovirus DNA Load Help to Reach Consensus Criteria for Triggering the Initiation of Preemptive Antiviral Therapy in Transplant Recipients? Clin Infect Dis. 2016;63(11):1533-1535. doi:10.1093/cid/ciw608
33. Ljungman P, Boeckh M, Hirsch HH, et al. Definitions of Cytomegalovirus Infection and Disease in Transplant Patients for Use in Clinical Trials. Clin Infect Dis. 2017;64(1):87-91. doi:10.1093/cid/ciw668
34. Boeckh M, Stevens-Ayers T, Travi G, et al. Cytomegalovirus (CMV) DNA Quantitation in Bronchoalveolar Lavage Fluid From Hematopoietic Stem Cell Transplant Recipients With CMV Pneumonia. J Infect Dis. 2017;215(10):1514-1522. doi:10.1093/infdis/jix048
35. Pinana JL, Gimenez E, Gomez MD, et al. Pulmonary cytomegalovirus (CMV) DNA shedding in allogeneic hematopoietic stem cell transplant recipients: Implications for the diagnosis of CMV pneumonia. J Infect. 2019;78(5):393-401. doi:10.1016/j.jinf.2019.02.009
36. Suárez-Lledó M, Marcos MÁ, Cuatrecasas M, et al. Quantitative PCR Is Faster, More Objective, and More Reliable Than Immunohistochemistry for the Diagnosis of Cytomegalovirus Gastrointestinal Disease in Allogeneic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2019;25(11):2281-2286. doi:10.1016/j.bbmt.2019.07.016
37. Romero PP, Blanco P, Giménez E, Solano C, Navarro D. An update on the management and prevention of cytomegalovirus infection following allogeneic hematopoietic stem cell transplantation. Future Virol. 2015;10(2). doi:10.2217/fvl.14.102
38. Meesing A, Razonable RR. Pharmacologic and immunologic management of cytomegalovirus infection after solid organ and hematopoietic stem cell transplantation. Expert Rev Clin Pharmacol. 2018;11(8):773-788. doi:10.1080/17512433.2018.1501557
39. Khanna R. Immune Monitoring of Infectious Complications in Transplant Patients: an Important Step towards Improved Clinical Management. J Clin Microbiol. 2018;56(4). doi:10.1128/JCM.02009-17
40. Navarro D, Amat P, de la Camara R, et al. 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. Open forum Infect Dis. 2016;3(2):ofw107. doi:10.1093/ofid/ofw107
41. Avetisyan G, Aschan J, Hagglund H, Ringden O, Ljungman P. Evaluation of intervention strategy based on CMV-specific immune responses after allogeneic SCT. Bone Marrow Transplant. 2007;40(9):865-869. doi:10.1038/sj.bmt.1705825
42. Chen K, Cheng MP, Hammond SP, Einsele H, Marty FM. Antiviral prophylaxis for cytomegalovirus infection in allogeneic hematopoietic cell transplantation. Blood Adv. 2018;2(16):2159-2175. doi:10.1182/bloodadvances.2018016493
43. Bacigalupo A, Tedone E, Van Lint MT, et al. CMV prophylaxis with foscarnet in allogeneic bone marrow transplant recipients at high risk of developing CMV infections. Bone Marrow Transplant. 1994;13(6):783-788.
44. Bregante S, Bertilson S, Tedone E, et al. Foscarnet prophylaxis of cytomegalovirus infections in patients undergoing allogeneic bone marrow transplantation (BMT): a dose-finding study. Bone Marrow Transplant. 2000;26(1):23-29. doi:10.1038/sj.bmt.1702450
45. Marty FM, Ljungman P, Papanicolaou GA, et al. Maribavir prophylaxis for prevention of cytomegalovirus disease in recipients of allogeneic stem-cell transplants: a phase 3, double-blind, placebo-controlled, randomised trial. Lancet Infect Dis. 2011;11(4):284-292. doi:10.1016/S1473-3099(11)70024-X
46. Marty FM, Winston DJ, Chemaly RF, et al. A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial of Oral Brincidofovir for Cytomegalovirus Prophylaxis in Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2019;25(2):369-381. doi:10.1016/j.bbmt.2018.09.038
47. Marty FM, Ljungman P, Chemaly RF, et al. Letermovir Prophylaxis for Cytomegalovirus in Hematopoietic-Cell Transplantation. N Engl J Med. 2017;377(25):2433-2444. doi:10.1056/NEJMoa1706640
48. Gagelmann N, Ljungman P, Styczynski J, Kroger N. Comparative Efficacy and Safety of Different Antiviral Agents for Cytomegalovirus Prophylaxis in Allogeneic Hematopoietic Cell Transplantation: A Systematic Review and Meta-Analysis. Biol Blood Marrow Transplant. 2018;24(10):2101-2109. doi:10.1016/j.bbmt.2018.05.017
49. Goldsmith SR, Slade M, DiPersio JF, et al. Cytomegalovirus viremia, disease, and impact on relapse in T-cell replete peripheral blood haploidentical hematopoietic cell transplantation with post-transplant cyclophosphamide. Haematologica. 2016;101(11):e465-e468. doi:10.3324/haematol.2016.149880
50. Huntley D, Giménez E, Pascual MJ, et al. Incidence, features, and outcomes of cytomegalovirus DNAemia in unmanipulated haploidentical allogeneic hematopoietic stem cell transplantation with post-transplantation cyclophosphamide. Transpl Infect Dis. 2020;22(1):1-9. doi:10.1111/tid.13206
51. Goldsmith SR, Abid MB, Auletta JJ, et al. Posttransplant cyclophosphamide is associated with increased cytomegalovirus infection: a CIBMTR analysis. Blood. 2021;137(23):3291-3305. doi:10.1182/blood.2020009362
52. Russo D, Schmitt M, Pilorge S, et al. Efficacy and safety of extended duration letermovir prophylaxis in recipients of haematopoietic stem-cell transplantation at risk of cytomegalovirus infection: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Haematol. 2024;11(2):e127-e135. doi:10.1016/S2352-3026(23)00344-7.
53. Perchetti GA, Biernacki MA, Xie H, et al. Cytomegalovirus breakthrough and resistance during letermovir prophylaxis. Bone Marrow Transplant. 2023;58(4):430-436. doi:10.1038/s41409-023-01920-w
54. Mizuno K, Sakurai M, Kato J, et al. Risk factor analysis for cytomegalovirus reactivation under prophylaxis with letermovir after allogeneic hematopoietic stem cell transplantation. Transpl Infect Dis. 2022;24(6):1-9. doi:10.1111/tid.13904
55. Huntley D, Talaya A, Giménez E, et al. Features of Cytomegalovirus DNAemia Blips in Allogeneic Hematopoietic Stem Cell Transplant Recipients: Implications for Optimization of Preemptive Antiviral Therapy Strategies. Biol Blood Marrow Transplant. 2020;26(5):972-977. doi:10.1016/j.bbmt.2020.01.015
56. Giménez E, Guerreiro M, Torres I, et al. Features of cytomegalovirus DNAemia and virus-specific T-cell responses in allogeneic hematopoietic stem-cell transplant recipients during prophylaxis with letermovir. Transpl Infect Dis. 2023;25(2):1-10. doi:10.1111/tid.14021
57. Chaer F El, Shah DP, Chemaly RF. How i treat resistant cytomegalovirus infection in hematopoietic cell transplantation recipients. Blood. 2016;128(23):2624-2636. doi:10.1182/blood-2016-06-688432
58. Lin A, Maloy M, Su Y, et al. Letermovir for primary and secondary cytomegalovirus prevention in allogeneic hematopoietic cell transplant recipients: Real-world experience. Transpl Infect Dis. 2019;21(6):e13187. doi:10.1111/tid.13187
59. Su Y, Stern A, Karantoni E, et al. Impact of Letermovir Primary Cytomegalovirus Prophylaxis on 1-Year Mortality After Allogeneic Hematopoietic Cell Transplantation: A Retrospective Cohort Study. Clin Infect Dis. 2022;(January 2013):1-10. doi:10.1093/cid/ciab1064
60. Anderson A, Raja M, Vazquez N, Morris M, Komanduri K, Camargo J. Clinical “real-world” experience with letermovir for prevention of cytomegalovirus infection in allogeneic hematopoietic cell transplant recipients. Clin Transplant. 2020;34(7):1-8. doi:10.1111/ctr.13866
61. Robin C, Thiebaut A, Alain S, et al. Letermovir for Secondary Prophylaxis of Cytomegalovirus Infection and Disease after Allogeneic Hematopoietic Cell Transplantation: Results from the French Compassionate Program. Biol Blood Marrow Transplant. 2020;26(5):978-984. doi:10.1016/j.bbmt.2020.01.027
62. Chemaly RF, Ullmann AJ, Stoelben S, et al. Letermovir for cytomegalovirus prophylaxis in hematopoietic-cell transplantation. N Engl J Med. 2014;370(19):1781-1789. doi:10.1056/NEJMoa1309533
63. El Helou G, Razonable RR. Letermovir for the prevention of cytomegalovirus infection and disease in transplant recipients: an evidence-based review. Infect Drug Resist. 2019;12:1481-1491. doi:10.2147/IDR.S180908
64. Restelli U, Croce D, Pacelli V, Ciceri F, Girmenia C. Cost-effectiveness analysis of the use of letermovir for the prophylaxis of cytomegalovirus in adult cytomegalovirus seropositive recipients undergoing allogenic hematopoietic stem cell transplantation in Italy. Infect Drug Resist. 2019;12:1127-1138. doi:10.2147/IDR.S196282
65. Reusser P, Einsele H, Lee J, et al. Randomized multicenter trial of foscarnet versus ganciclovir for preemptive therapy of cytomegalovirus infection after allogeneic stem cell transplantation. Blood. 2002;99(4):1159-1164. doi:10.1182/blood.V99.4.1159
66. Papanicolaou GA, Avery RK, Cordonnier C, et al. Treatment for First Cytomegalovirus Infection Post–Hematopoietic Cell Transplant in the AURORA Trial: A Multicenter, Double-Blind, Randomized, Phase 3 Trial Comparing Maribavir With Valganciclovir. Clin Infect Dis. 2024;78(3):562-572. doi:10.1093/cid/ciad709
67. Solano C, Giménez E, Piñana JL, et al. When should preemptive antiviral therapy for active CMV infection be withdrawn from allogeneic stem cell transplant recipients? Bone Marrow Transplant. 2017;52(10):1448-1451. doi:10.1038/bmt.2017.109
68. Chemaly RF, Chou S, Einsele H, et al. Definitions of Resistant and Refractory Cytomegalovirus Infection and Disease in Transplant Recipients for Use in Clinical Trials. Clin Infect Dis. 2019;68(8):1420-1426. doi:10.1093/cid/ciy696
69. Khawaja F, Batista M V., El Haddad L, Chemaly RF. Resistant or refractory cytomegalovirus infections after hematopoietic cell transplantation: Diagnosis and management. Curr Opin Infect Dis. Published online 2019:565-574. doi:10.1097/QCO.0000000000000607
70. Khawaja F, Spallone A, Kotton CN, Chemaly RF. Cytomegalovirus infection in transplant recipients: newly approved additions to our armamentarium. Clin Microbiol Infect. 2023;29(1):44-50. doi:10.1016/j.cmi.2022.07.001
71. Shmueli E, Or R, Shapira MY, et al. High rate of cytomegalovirus drug resistance among patients receiving preemptive antiviral treatment after haploidentical stem cell transplantation. J Infect Dis. 2014;209(4):557-561. doi:10.1093/infdis/jit475
72. Fischer L, Imrich E, Sampaio KL, et al. Identification of resistance-associated HCMV UL97- and UL54-mutations and a UL97-polymporphism with impact on phenotypic drug-resistance. Antiviral Res. 2016;131:1-8. doi:10.1016/j.antiviral.2016.04.002
73. Chou S. Approach to drug-resistant cytomegalovirus in transplant recipients. Curr Opin Infect Dis. 2015;28(4):293-299. doi:10.1097/QCO.0000000000000170
74. Chou S. Advances in the genotypic diagnosis of cytomegalovirus antiviral drug resistance. Antiviral Res. 2020;176:104711. doi:10.1016/j.antiviral.2020.104711
75. Lopez-Aladid R, Guiu A, Sanclemente G, et al. Detection of cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance. J Clin Virol. 2017;90:57-63. doi:10.1016/j.jcv.2017.03.014
76. Lopez-Aladid R, Guiu A, Mosquera MM, et al. Improvement in detecting cytomegalovirus drug resistance mutations in solid organ transplant recipients with suspected resistance using next generation sequencing. PLoS One. 2019;14(7):e0219701. doi:10.1371/journal.pone.0219701
77. Chou S, Ercolani RJ, Derakhchan K. Antiviral activity of maribavir in combination with other drugs active against human cytomegalovirus. Antiviral Res. 2018;157:128-133. doi:10.1016/j.antiviral.2018.07.013
78. Avery RK, Alain S, Alexander BD, et al. Maribavir for Refractory Cytomegalovirus Infections With or Without Resistance Post-Transplant: Results From a Phase 3 Randomized Clinical Trial. Clin Infect Dis. 2022;75(4):690-701. doi:10.1093/cid/ciab988
79. Quach DH, Lulla P, Rooney CM. Banking on virus-specific T cells to fulfill the need for off-the-shelf cell therapies. Blood. 2023;141(8):877-885. doi:10.1182/blood.2022016202
80. Mahadeo KM, Baiocchi R, Beitinjaneh A, et al. Tabelecleucel for allogeneic haematopoietic stem-cell or solid organ transplant recipients with Epstein-Barr virus-positive post-transplant lymphoproliferative disease after failure of rituximab or rituximab and chemotherapy (ALLELE ). Lancet Oncol. 2024;25(3):376-387. doi:10.1016/S1470-2045(23)00649-6
81. Roex MCJ, van Balen P, Germeroth L, et al. Generation and infusion of multi-antigen-specific T cells to prevent complications early after T-cell depleted allogeneic stem cell transplantation—a phase I/II study. Leukemia. 2020;34(3):831-844. doi:10.1038/s41375-019-0600-z
82. Prockop SE, Hasan A, Doubrovina E, et al. Third-party cytomegalovirus-specific T cells improved survival in refractory cytomegalovirus viremia after hematopoietic transplant. J Clin Invest. 2023;133(10). doi:10.1172/JCI165476
83. Pfeiffer T, Tzannou I, Wu M, et al. Posoleucel, an Allogeneic, Off-the-Shelf Multivirus-Specific T-Cell Therapy, for the Treatment of Refractory Viral Infections in the Post-HCT Setting. Clin Cancer Res. 2023;29(2):3240330. doi:10.1158/1078-0432.CCR-22-2415
84. Pescovitz MD, Ettenger RB, Strife CF, et al. Pharmacokinetics of oral valganciclovir solution and intravenous ganciclovir in pediatric renal and liver transplant recipients. Transpl Infect Dis. 2010;12(3):195-203. doi:10.1111/j.1399-3062.2009.00478.x
85. Vaudry W, Ettenger R, Jara P, et al. Valganciclovir dosing according to body surface area and renal function in pediatric solid organ transplant recipients. Am J Transplant. 2009;9(3):636-643. doi:10.1111/j.1600-6143.2008.02528.x
86. Pescovitz MD, Jain A, Robson R, Mulgaonkar S, Freeman R, Bouw MR. Establishing pharmacokinetic bioequivalence of valganciclovir oral solution versus the tablet formulation. Transplant Proc. 2007;39(10):3111-3116. doi:10.1016/j.transproceed.2007.10.007
87. Martin M, Goyette N, Ives J, Boivin G. Incidence and characterization of cytomegalovirus resistance mutations among pediatric solid organ transplant patients who received valganciclovir prophylaxis. J Clin Virol. 2010;47(4):321-324. doi:10.1016/j.jcv.2010.01.009
88. Groll AH, Schulte JH, Antmen AB, et al. Pharmacokinetics, Safety, and Efficacy of Letermovir for Cytomegalovirus Prophylaxis in Adolescent Hematopoietic Cell Transplantation Recipients. Pediatr Infect Dis J. 2024;43(3):203-208. doi:10.1097/inf.0000000000004208
89. Feucht J, Opherk K, Lang P, et al. Adoptive T-cell therapy with hexon-specific Th1 cells as a treatment of refractory adenovirus infection after HSCT. Blood. 2015;125(12):1986-1994. doi:10.1182/blood-2014-06-573725
90. Scheinberg P, Melenhorst JJ, Brenchley JM, et al. The transfer of adaptive immunity to CMVduring hematopoietic stem cell transplantation is dependent on the specificity and phenotype of CMV-specific T cells in the donor. Blood. 2009;114(24):5071-5080. doi:10.1182/blood-2009-04-214684
91. Gottlieb D, Jiang W, Avdic S, et al. Administration of Third-Party Virus-Specific T-Cells (VST) at the Time of Initial Therapy for Infection after Haemopoietic Stem Cell Transplant Is Safe and Associated with Favourable Clinical Outcomes (the REACT-Quickly trial). Blood. 2019;134(Supplement_1):251. doi:10.1182/blood-2019-125166
92. Gottlieb DJ, Clancy LE, Withers B, et al. Prophylactic antigen-specific T-cells targeting seven viral and fungal pathogens after allogeneic haemopoietic stem cell transplant. Clin Transl Immunol. 2021;10(3):1-18. doi:10.1002/cti2.1249