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 Infectious Diseases

Volumn 3, Issue 2, 2016, Pages

  Navarro, David ^a,b   Amat, Paula ^a   de la Cámara, Rafael ^c   López, Javier ^d   Vázquez, Lourdes ^e   Serrano, David ^f,g   Nieto, José ^g   Rovira, Monserrat ^h   Piñana, José Luis ^a   Giménez, Estela ^a   Solano, Carloson ^a,b  

^a HOSPITAL CLÍNICO UNIVERSITARIO   (Spain)

^b UNIVERSITY OF VALENCIA   (Spain)

^c HOSPITAL UNIVERSITARIO DE LA PRINCESA   (Spain)

^d HOSPITAL RAMÓN Y CAJAL   (Spain)

^e HOSPITAL UNIVERSITARIO DE SALAMANCA   (Spain)

^f HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑÓN   (Spain)

^g HOSPITAL MORALES MESEGUER   (Spain)

^h HOSPITAL CLÍNIC   (Spain)

Author keywords

Allogeneic stem cell transplantation; Cytomegalovirus; IFN CD8+ T cells; Immunological monitoring; Preemptive antiviral therapy

Indexed keywords

CD69 ANTIGEN; CYTOMEGALOVIRUS ANTIGEN PP65; FOSCARNET; GAMMA1B INTERFERON; GANCICLOVIR; PHOSPHOPROTEIN; VALGANCICLOVIR;

ADULT; ALLOGENEIC STEM CELL TRANSPLANTATION; ANTIVIRAL THERAPY; ARTICLE; CD3+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; COMPARATIVE STUDY; CONTROLLED STUDY; CYTOMEGALOVIRUS INFECTION; FEMALE; FLOW CYTOMETRY; GRAFT RECIPIENT; HUMAN; HUMAN CELL; IMMUNOLOGICAL MONITORING; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; NEUTROPENIA; PHASE 3 CLINICAL TRIAL; PRIORITY JOURNAL; PROSPECTIVE STUDY; RANDOMIZED CONTROLLED TRIAL; REAL TIME POLYMERASE CHAIN REACTION; THROMBOCYTOPENIA; VIRUS LOAD;

EID: 84995676806     PISSN: None     EISSN: 23288957     Source Type: Journal    
DOI: 10.1093/ofid/ofw107     Document Type: Article

References (25)

1. Boeckh M, Ljungman P. How we treat cytomegalovirus in hematopoietic cell transplant recipients. Blood 2009; 113:5711-9.
2. Ljungman P, de la Camara R, Cordonnier C, et al. Management of CMV, HHV-6, HHV-7 and Kaposi-sarcoma herpesvirus (HHV-8) infections in patients with hematological malignancies and after SCT. Bone Marrow Transplant 2008; 42:227-40.
3. Tomblyn M, Chiller T, Einsele H, et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant 2009; 15:1143-238.
4. Pérez Romero P, Blanco P, Giménez E, et al. An update on the management and prevention of cytomegalovirus infection following allogeneic hematopoietic stem cell transplantation. Future Virol 2015; 10:113-34.
5. Solano C, de la Cámara R, Vázquez L, et al. Cytomegalovirus infection management in allogeneic stem cell transplant recipients: a National Survey in Spain. J Clin Microbiol 2015; 53:2741-4.
6. Solano C, Muñoz-Cobo B, Giménez E, et al. Pre-emptive antiviral therapy for active CMV infection in adult allo-SCT patients guided by plasma CMV DNAemia quantitation using a real-time PCR assay: Clinical experience at a single center. Bone Marrow Transplant 2013; 48:1010-2.
7. Boeckh M, Nichols WG, Chemaly RF, et al. Valganciclovir for the prevention of complications of late cytomegalovirus infection after allogeneic hematopoietic cell transplantation: a randomized trial. Ann Intern Med 2015; 162:1-10.
8. Quinnan GV, Kirmani N, Rook AH, et al. Cytotoxic T cells in cytomegalovirus infection: HLA-restricted T-lymphocyte and non T-lymphocyte cytotoxic responses correlate with recovery from cytomegalovirus infection in bonemarrow-transplant recipients. N Engl J Med 1982; 307:7-13.
9. Reusser P, Riddell SR, Meyers JD, Greenberg PD. Cytotoxic T-lymphocyte response to cytomegalovirus after human allogeneic bone marrow transplantation: pattern of recovery and correlation with cytomegalovirus infection and disease. Blood 1991; 78:1373-80.
10. Riddell SR, Watanabe KS, Goodrich JM, et al. Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones. Science 1992; 257:238-41.
11. Li CR, Greenberg PD, Gilbert MJ, et al. Recovery of HLA-restricted cytomegalovirus (CMV)-specific T-cell responses after allogeneic bone marrow transplant: correlation with CMV disease and effect of ganciclovir prophylaxis. Blood 1994; 83:1971-9.
12. Einsele H, Roosnek E, Rufer N, et al. Infusion of cytomegalovirus (CMV)-specific T-cells for the treatment of CMV infection not responding to antiviral chemotherapy. Blood 2002; 99:3916-22.
13. Tormo N, Solano C, Benet I, et al. Lack of prompt expansion of cytomegalovirus pp65 and IE-1-specific IFNgamma CD8+ and CD4+ T cells is associated with rising levels of pp65 antigenemia and DNAemia during pre-emptive therapy in allogeneic hematopoietic stem cell transplant recipients. Bone Marrow Transplant 2010; 45:543-9.
14. Tormo N, Solano C, Benet I, et al. Kinetics of cytomegalovirus (CMV) pp65 and IE-1-specific IFNgamma CD8+ and CD4+ T cells during episodes of viral DNAemia in allogeneic stem cell transplant recipients: potential implications for the management of active CMV infection. J Med Virol 2010; 82:1208-15.
15. Ljungman P. Would monitoring CMV immune responses allow improved control of CMV in stem cell transplant patients. J Clin Virol 2006; 35:493-5.
16. Avetisyan G, Aschan J, Hägglund H, et al. Evaluation of intervention strategy based on CMV-specific immune responses after allogeneic SCT. Bone Marrow Transplant 2007; 40:865-9.
17. Solano C, Benet I, Remigia MJ, et al. Immunological monitoring for guidance of preemptive antiviral therapy for active cytomegalovirus infection in allogeneic stem-cell transplant recipients: a pilot experience. Transplantation 2011; 92: e17-20.
18. Ljungman P, Griffiths P, Paya C. Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis 2002; 34:1094-7.
19. Solano C, Benet I, Clari MA, et al. Enumeration of cytomegalovirus-specific interferongamma CD8+ and CD4+ T cells early after allogeneic stem cell transplantation may identify patients at risk of active cytomegalovirus infection. Haematologica 2008; 93:1434-6.
20. San-Juan R, Navarro D, García-Reyne A, et al. Effect of long-term prophylaxis in the development of cytomegalovirus-specific T-cell immunity in D+/R-solid organ transplant recipients. Transpl Infect Dis 2015; 17:637-46.
21. Salzberger B, Bowden RA, Hackman RC, et al. Neutropenia in allogeneic marrow transplant recipients receiving ganciclovir for prevention of cytomegalovirus disease: risk factors and outcome. Blood 1997; 90:2502-8.
22. Venton G, Crocchiolo R, Fürst S, et al. Risk factors of ganciclovir-related neutropenia after allogeneic stem cell transplantation: a retrospective monocentre study on 547 patients. Clin Microbiol Infect 2014; 20:160-6.
23. Hakki M, Riddell SR, Storek J, et al. Immune reconstitution to cytomegalovirus after allogeneic hematopoietic stem cell transplantation: impact of host factors, drug therapy, and subclinical reactivation. Blood 2003; 102:3060-7.
24. Lilleri D, Fornara C, Chiesa A, et al. Human cytomegalovirus-specific CD4+ and CD8+ T-cell reconstitution in adult allogeneic hematopoietic stem cell transplant recipients and immune control of viral infection. Haematologica 2008; 93:248-53.
25. Tormo N, Solano C, Benet I, et al. Reconstitution of CMV pp65 and IE-1-specific IFN-γ CD8(+) and CD4(+) T-cell responses affording protection from CMV DNAemia following allogeneic hematopoietic SCT. Bone Marrow Transplant 2011; 46:1437-43.