Management of Cytomegalovirus Infection in Allogeneic Hematopoietic Stem Cell Transplant Recipients
DOI:
https://doi.org/10.20344/amp.21441Keywords:
Antiviral Agents/therapeutic use, Cytomegalovirus Infections/drug therapy, Cytomegalovirus Infections/etiology, Cytomegalovirus Infections/ prevention & control, Hematopoietic Stem Cell Transplantation/ adverse effectsAbstract
Cytomegalovirus (CMV) is a type of double-stranded deoxyribonucleic acid virus belonging to the herpesviridae family. Following a primary infection, the virus becomes latent in various types of white blood cells. Cytomegalovirus infection can remain latent or become active, especially in immunocompromised individuals, such as those undergoing hematopoietic stem cell transplantation (HSCT), where CMV reactivation can occur. In this context, CMV infection is common and associated with high rates of morbidity and mortality. Pneumonia is one of the most serious complications, with mortality rates exceeding 50%. Additionally, even in the absence of organ-specific disease, CMV infection is related to increased mortality unrelated to hematologic neoplasm recurrence. Given the frequency and severity of this infection in HSCT patients, it is crucial to implement effective strategies for monitoring, prevention, and treatment. This guideline was developed to identify patient groups that benefit from a systematic approach to CMV infection and to define the most appropriate strategy for each group. Monitoring CMV viral load in peripheral blood is crucial, especially in patients at moderate to high risk of active infection. Primary prophylaxis with letermovir (an antiviral drug) is recommended to reduce the incidence of active infection, especially in high-risk patients. Secondary prophylaxis with valganciclovir (antiviral drug) is recommended after an episode of active infection, while preemptive and disease treatment is based on monitoring viral load and clinical response. The aim of this guideline is to improve the approach to CMV infection in HSCT patients, ensuring an effective and safe preventive and therapeutic approach.
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Crough T, Khanna R. Immunobiology of human cytomegalovirus: from bench to bedside. Clin Microbiol Rev. 2009;22:76-98. DOI: https://doi.org/10.1128/CMR.00034-08
Gilioli A, Messerotti A, Bresciani P, Cuoghi A, Pioli V, Colasante C, et al. Cytomegalovirus reactivation after hematopoietic stem cell transplant with CMVIG prophylaxis: a monocentric retrospective analysis. J Med Virol. 2021;93:6292-300. DOI: https://doi.org/10.1002/jmv.26861
Meyers JD, Flournoy N, Thomas ED. Risk factors for cytomegalovirus infection after human marrow transplantation. J Infect Dis. 1986;153:478-88. DOI: https://doi.org/10.1093/infdis/153.3.478
Einsele H, Ljungman P, Boeckh M. How I treat CMV reactivation after allogeneic hematopoietic stem cell transplantation. Blood. 2020;135:1619-29. DOI: https://doi.org/10.1182/blood.2019000956
Ljungman P, Hakki M, Boeckh M. Cytomegalovirus in hematopoietic stem cell transplant recipients. Hematol Oncol Clin North Am. 2011;25:151-69. DOI: https://doi.org/10.1016/j.hoc.2010.11.011
Teira P, Battiwalla M, Ramanathan M, Barrett AJ, Ahn KW, Chen M, et al. Early cytomegalovirus reactivation remains associated with increased transplantrelated mortality in the current era: a CIBMTR analysis. Blood. 2016;127:2427-38. DOI: https://doi.org/10.1182/blood-2015-11-679639
George B, Pati N, Gilroy N, Ratnamohan M, Huang G, Kerridge I, et al. Pre-transplant cytomegalovirus (CMV) serostatus remains the most important determinant of CMV reactivation after allogeneic hematopoietic stem cell transplantation in the era of surveillance and preemptive therapy. Transpl Infect Dis. 2010;12:322-9. DOI: https://doi.org/10.1111/j.1399-3062.2010.00504.x
Boeckh M, Nichols WG, Papanicolaou G, Rubin R, Wingard JR, Zaia J. Cytomegalovirus in hematopoietic stem cell transplant recipients: current status, known challenges, and future strategies. Biol Blood Marrow Transplant. 2003;9:543-58. DOI: https://doi.org/10.1016/S1083-8791(03)00287-8
Sousa H, Boutolleau D, Ribeiro J, Teixeira AL, Pinho Vaz C, Campilho F, et al. Cytomegalovirus infection in patients who underwent allogeneic hematopoietic stem cell transplantation in Portugal: a five-year retrospective review. Biol Blood Marrow Transplant. 2014;20:1958-67. DOI: https://doi.org/10.1016/j.bbmt.2014.08.010
Goldsmith SR, Abid MB, Auletta JJ, Bashey A, Beitinjaneh A, Castillo P, et al. Posttransplant cyclophosphamide is associated with increased cytomegalovirus infection: a CIBMTR analysis. Blood. 2021;137:3291-305. DOI: https://doi.org/10.1182/blood.2020009362
Hakki M, Aitken SL, Danziger-Isakov L, Michaels MG, Carpenter PA, Chemaly RF, 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;27:707-19. DOI: https://doi.org/10.1016/j.jtct.2021.05.001
Marty FM, Ljungman P, Chemaly RF, Maertens J, Dadwal SS, Duarte RF, et al. Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation. N Engl J Med. 2017;377:2433-44. DOI: https://doi.org/10.1056/NEJMoa1706640
Schmidt-Hieber M, Schwarck S, Stroux A, Ganepola S, Reinke P, Thiel E, et al. Immune reconstitution and cytomegalovirus infection after allogeneic stem cell transplantation: the important impact of in vivo T cell depletion. Int J Hematol. 2010;91:877-85. DOI: https://doi.org/10.1007/s12185-010-0597-6
Ljungman P, Griffiths P, Paya C. Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis. 2002;34:1094-7. DOI: https://doi.org/10.1086/339329
Ljungman P, de la Camara R, Robin C, Crocchiolo R, Einsele H, Hill JA, 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:e260-72. DOI: https://doi.org/10.1016/S1473-3099(19)30107-0
European Medicines Agency. Letermovir. [consultado 2024 fev 28]. Disponível em: https://www.ema.europa.eu/en/medicines/human/EPAR/prevymis.
Food and Drug Adminisration. Prevymis full prescribing information. [consultado 2024 fev 28]. Disponível em: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209939Orig1s000,209940Orig1s000lbl.pdf.
World Health Organization. Training manual for Enzyme linked immunosorbent assay for the quantitation of Streptococcus pneumoniae serotype specific IgG. [consultado 2014 jun 28]. Disponível em: https://ww3.icb.usp.br/wp-content/uploads/2020/10/PROTOCOLO-ELISA.pdf.
Malagola M, Greco R, El Cheikh J. Editorial: 50 years of BMT: conditioning regimens and early complications after transplantation. Front Oncol. 2024;14:1369573. DOI: https://doi.org/10.3389/fonc.2024.1369573
Robin C, Thiebaut A, Alain S, Sicre de Fontbrune F, Berceanu A, D'Aveni M, 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;26:978-84. DOI: https://doi.org/10.1016/j.bbmt.2020.01.027
Green ML, Leisenring W, Stachel D, Pergam SA, Sandmaier BM, Wald A, et al. Efficacy of a viral load-based, risk-adapted, preemptive treatment strategy for prevention of cytomegalovirus disease after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2012;18:1687-99. DOI: https://doi.org/10.1016/j.bbmt.2012.05.015
Marty FM, Ljungman PT, Chemaly RF, Wan H, Teal VL, Butterton JR, et al. Outcomes of patients with detectable CMV DNA at randomization in the phase III trial of letermovir for the prevention of CMV infection in allogeneic hematopoietic cell transplantation. Am J Transplant. 2020;20:1703-11. DOI: https://doi.org/10.1111/ajt.15764
Reusser P, Einsele H, Lee J, Volin L, Rovira M, Engelhard D, et al. Randomized multicenter trial of foscarnet versus ganciclovir for preemptive therapy of cytomegalovirus infection after allogeneic stem cell transplantation. Blood. 2002;99:1159-64. DOI: https://doi.org/10.1182/blood.V99.4.1159
Avery RK, Alain S, Alexander BD, Blumberg EA, Chemaly RF, Cordonnier C, 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;75:690-701. DOI: https://doi.org/10.1093/cid/ciab988
Razonable RR. Oral antiviral drugs for treatment of cytomegalovirus in transplant recipients. Clin Microbiol Infect. 2023;29:1144-9. DOI: https://doi.org/10.1016/j.cmi.2023.03.020
European Medicines Agency. Maribavir. [consultado 2024 fev 28]. Disponível em: https://www.ema.europa.eu/en/medicines/human/EPAR/livtencity.
European Medicines Agency. Ganciclovir. [consultado 2024 fev 28]. Disponível em: https://www.ema.europa.eu/en/medicines/human/referrals/cymevene.
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