Cytomegalovirus reactivation after hematopoietic stem cell transplant with CMV-IG prophylaxis: A monocentric retrospective analysis.
Adolescent
Adult
Antibodies, Viral
/ administration & dosage
Antiviral Agents
/ administration & dosage
Cytomegalovirus
/ genetics
Cytomegalovirus Infections
/ immunology
Female
Hematopoietic Stem Cell Transplantation
/ adverse effects
Humans
Immunoglobulin G
/ administration & dosage
Male
Middle Aged
Pre-Exposure Prophylaxis
Recurrence
Retrospective Studies
Virus Activation
Young Adult
CMV
CMV prophylaxis
CMV-specific immunoglobulins
hematopoietic stem cell transplantation
Journal
Journal of medical virology
ISSN: 1096-9071
Titre abrégé: J Med Virol
Pays: United States
ID NLM: 7705876
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
13
10
2020
accepted:
03
02
2021
pubmed:
14
2
2021
medline:
30
12
2021
entrez:
13
2
2021
Statut:
ppublish
Résumé
Human cytomegalovirus (CMV) represents the most common viral infection after hematopoietic stem cell transplant (HSCT), mainly occurring as reactivation from latency in seropositive patients, with a different prevalence based on the extent and timing of seroconversion in a specific population. Here, we retrospectively analyzed a cohort of patients who underwent HSCT at our Institution between 2013 and 2018, all of whom were prophylactically treated with CMV-IG (Megalotect Biotest®), to define the incidence and clinical outcomes of CMV reactivation and clinically significant infection. CMV infection occurred in 69% of our patient series, mainly resulting from reactivation, and CMV clinically significant infection (CS-CMVi) occurred in 48% of prophylactically treated patients. CMV infection and CS-CMVi impacted neither on relapse incidence nor on overall survival nor on relapse-free survival. Moreover, a very low incidence of CMV end-organ disease was documented. CMV-IG used alone as prophylactic therapy after HSCT does not effectively prevent CMV reactivation.
Substances chimiques
Antibodies, Viral
0
Antiviral Agents
0
Immunoglobulin G
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6292-6300Informations de copyright
© 2021 Wiley Periodicals LLC.
Références
Griffiths P , Baraniak I , Reeves M . The pathogenesis of human cytomegalovirus. J Pathol. 2015;235(2):288-297.
de la Camara R . CMV in hematopoietic stem cell transplantation. Mediterr J Hematol Infect Dis. 2016;8(1):e2016031.
Locatelli F , Bertaina A , Bertaina V , Merli P . Cytomegalovirus in hematopoietic stem cell transplant recipients - management of infection. Expert Rev Hematol. 2016;9(11):1093-1105.
Maffini E , Giaccone L , Festuccia M , Brunello L , Busca A , Bruno B . Treatment of CMV infection after allogeneic hematopoietic stem cell transplantation. Expert Rev Hematol. 2016;9(6):585-596.
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.
Melendez-Munoz R , Marchalik R , Jerussi T , et al. Cytomegalovirus infection incidence and risk factors across diverse hematopoietic cell transplantation platforms using a standardized monitoring and treatment approach: a comprehensive evaluation from a single institution. Biol Blood Marrow Transplant. 2018;25(3):577-586.
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.
Stern L , Withers B , Avdic S , et al. Human cytomegalovirus latency and reactivation in allogeneic hematopoietic stem cell transplant recipients. Front Microbiol. 2019;10:1186.
Hill JA , Mayer BT , Xie H , et al. The cumulative burden of double-stranded DNA virus detection after allogeneic HCT is associated with increased mortality. Blood. 2017;129(16):2316-2325.
Reddehase MJ , Lemmermann NAW . Cellular reservoirs of latent cytomegaloviruses. Med Microbiol Immunol. 2019;208(3-4):391-403.
Erard V , Guthrie KA , Seo S , et al. Reduced mortality of cytomegalovirus pneumonia after hematopoietic cell transplantation due to antiviral therapy and changes in transplantation practices. Clin Infect Dis. 2015;61(1):31-39.
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;3(3):e119-e127.
Teira P , Battiwalla M , Ramanathan M , et al. Early cytomegalovirus reactivation remains associated with increased transplant-related mortality in the current era: a CIBMTR analysis. Blood. 2016;127(20):2427-2438.
Hill JA , Mayer BT , Xie H , et al. Kinetics of double-stranded DNA viremia after allogeneic hematopoietic cell transplantation. Clin Infect Dis. 2018;66(3):368-375.
Webb BJ , Harrington R , Schwartz J , et al. The clinical and economic impact of cytomegalovirus infection in recipients of hematopoietic stem cell transplantation. Transpl Infect Dis. 2018;20(5):e12961.
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.
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.
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.
Messori A , Rampazzo R , Scroccaro G , Martini N . Efficacy of hyperimmune anti-cytomegalovirus immunoglobulins for the prevention of cytomegalovirus infection in recipients of allogeneic bone marrow transplantation: a meta-analysis. Bone Marrow Transplant. 1994;13(2):163-167.
King SM . Immune globulin versus antivirals versus combination for prevention of cytomegalovirus disease in transplant recipients. Antiviral Res. 1999;40(3):115-137.
Ahn H , Tay J , Shea B , et al. Effectiveness of immunoglobulin prophylaxis in reducing clinical complications of hematopoietic stem cell transplantation: a systematic review and meta-analysis. Transfusion. 2018;58(10):2437-2452.
Carbone J . The immunology of posttransplant CMV infection: potential effect of CMV immunoglobulins on distinct components of the immune response to CMV. Transplantation. 2016;100(suppl 3):S11-S18.
Fryer JFHA , Heath AB , Anderson R , Minor PD . Collaborative Study to Evaluate the Proposed 1st WHO International Standard for Human Cytomegalovirus (HCMV) for Nucleic Acid Amplification (NAT)-Based Assays. Geneva, Switzerland: World Health Organization; 2010. WHO/BS/10/2138.
Fryer JF , Heath AB , Minor PD , Collaborative Study Group. A collaborative study to establish the 1st WHO International Standard for human cytomegalovirus for nucleic acid amplification technology. Biologicals. 2016;44(4):242-251.
Harris AC , Young R , Devine S , et al. International, multicenter standardization of acute graft-versus-host disease clinical data collection: a report from the Mount Sinai Acute GVHD International consortium. Biol Blood Marrow Transplant. 2016;22(1):4-10.
Jagasia MH , Greinix HT , Arora M , et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015;21(3):389-401.
De Pauw B , Walsh TJ , Donnelly JP , et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46(12):1813-1821.
Bacigalupo A , Ballen K , Rizzo D , et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009;15(12):1628-1633.
Girmenia C , Barosi G , Piciocchi A , et al. Primary prophylaxis of invasive fungal diseases in allogeneic stem cell transplantation: revised recommendations from a consensus process by Gruppo Italiano Trapianto Midollo Osseo (GITMO). Biol Blood Marrow Transplant. 2014;20(8):1080-1088.
Malagola M , Greco R , Santarone S , et al. CMV management with specific immunoglobulins: a multicentric retrospective analysis on 92 allotransplanted patients. Mediterr J Hematol Infect Dis. 2019;11(1):e2019048.
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):e13866.
Lazzarotto T , Chiereghin A , Piralla A , et al. Cytomegalovirus and Epstein-Barr virus DNA kinetics in whole blood and plasma of allogeneic hematopoietic stem cell transplantation recipients. Biol Blood Marrow Transplant. 2018;24(8):1699-1706.
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:e13666.
Melendez-Munoz R , Marchalik R , Jerussi T , et al. Cytomegalovirus infection incidence and risk factors across diverse hematopoietic cell transplantation platforms using a standardized monitoring and treatment approach: a comprehensive evaluation from a single institution. Biol Blood Marrow Transplant. 2019;25(3):577-586.
Ljungman P , Brand R , Hoek J , et al. Donor cytomegalovirus status influences the outcome of allogeneic stem cell transplant: a study by the European group for blood and marrow transplantation. Clin Infect Dis. 2014;59(4):473-481.
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.
Elmaagacli AH , Steckel NK , Koldehoff M , et al. Early human cytomegalovirus replication after transplantation is associated with a decreased relapse risk: evidence for a putative virus-versus-leukemia effect in acute myeloid leukemia patients. Blood. 2011;118(5):1402-1412.
Green ML , Leisenring WM , Xie H , et al. CMV reactivation after allogeneic HCT and relapse risk: evidence for early protection in acute myeloid leukemia. Blood. 2013;122(7):1316-1324.
Takenaka K , Nishida T , Asano-Mori Y , et al. Cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation is associated with a reduced risk of relapse in patients with acute myeloid leukemia who survived to day 100 after transplantation: the Japan Society for Hematopoietic Cell Transplantation Transplantation-related Complication Working Group. Biol Blood Marrow Transplant. 2015;21(11):2008-2016.
Peric Z , Wilson J , Durakovic N , et al. Early human cytomegalovirus reactivation is associated with lower incidence of relapse of myeloproliferative disorders after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2018;53(11):1450-1456.
Yong MK , Slavin MA , Kontoyiannis DP . Invasive fungal disease and cytomegalovirus infection: is there an association? Curr Opin Infect Dis. 2018;31(6):481-489.
Janeczko M , Mielcarek M , Rybka B , Ryczan-Krawczyk R , Noworolska-Sauren D , Kalwak K . Immune recovery and the risk of CMV/EBV reactivation in children post allogeneic haematopoietic stem cell transplantation. Cent Eur J Immunol. 2016;41(3):287-296.
Hall CE , Koparde VN , Jameson-Lee M , et al. Sequence homology between HLA-bound cytomegalovirus and human peptides: a potential trigger for alloreactivity. PLOS One. 2017;12(8):e0178763.
Grefte A , van der Giessen M , van Son W , The TH . Circulating cytomegalovirus (CMV)-infected endothelial cells in patients with an active CMV infection. J Infect Dis. 1993;167(2):270-277.
Piñana JL , Perez-Pitarch A , Guglieri-Lopez B , et al. Sirolimus exposure and the occurrence of cytomegalovirus DNAemia after allogeneic hematopoietic stem cell transplantation. Am J Transplant. 2018;18(12):2885-2894.