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Published in: BMC Infectious Diseases 1/2017

Open Access 01-12-2017 | Research article

Economic burden of preemptive treatment of CMV infection after allogeneic stem cell transplantation: a retrospective study of 208 consecutive patients

Authors: Christine Robin, François Hémery, Christel Dindorf, Julien Thillard, Ludovic Cabanne, Rabah Redjoul, Florence Beckerich, Christophe Rodriguez, Cécile Pautas, Andrea Toma, Sébastien Maury, Isabelle Durand-Zaleski, Catherine Cordonnier

Published in: BMC Infectious Diseases | Issue 1/2017

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Abstract

Background

Cytomegalovirus (CMV) infection and disease (CMV episodes) are global concerns after allogeneic hematopoietic stem cell transplantation (HSCT). They affect survival, both by direct and indirect effects. Due to safety issues of current anti-CMV antivirals, long-term CMV prophylaxis is poorly tolerated and the most common strategy to decrease the incidence of CMV disease is preemptive. New, less toxic, molecules are currently being assessed for CMV prophylaxis which should replace or considerably decrease the preemptive approach. The aim of this study was to assess the economic burden of CMV episodes after HSCT with a preemptive approach.

Methods

We analyzed data from 208 consecutive adults transplanted in our institution, between 2008 and 2013. Hospital resource utilization was retrieved via the linked hospital admissions and Diagnostic Related Groups for the period of conditioning to 12 months after transplant.

Results

CMV episodes occurred in 70 patients (34%) over the first 12 months following HSCT, after a mean of 75 days (median: 46 (7–334)). The mean total length of stay was significantly associated with the occurrence of a CMV episode (113.9 vs. 87.5 days, p = 0.0002) but was associated neither with the pre-transplant CMV serology of donors/recipients nor with survival. The mean cost of transplant was €104,016 (SD = €37,281) after 12 months. Bivariate and multivariate analyses indicated that the occurrence of >1 CMV episode increased the costs of allogeneic HSCT by 25–30% (p < 0.0001).

Conclusion

Our study, which is the largest, single-institution cost study of allogeneic HSCT in Europe, shows that two or more CMV episodes significantly increased the transplant cost. New prophylactic strategies to prevent CMV infection and disease should decrease transplant costs.
Literature
1.
go back to reference Boeckh M, Murphy WJ, Peggs KS. Recent advances in cytomegalovirus: an update on pharmacologic and cellular therapies. Biol Blood Marrow Transplant. 2015;21(2 Suppl):S19–24.CrossRefPubMed Boeckh M, Murphy WJ, Peggs KS. Recent advances in cytomegalovirus: an update on pharmacologic and cellular therapies. Biol Blood Marrow Transplant. 2015;21(2 Suppl):S19–24.CrossRefPubMed
2.
go back to reference 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):2003–8.CrossRefPubMed 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):2003–8.CrossRefPubMed
3.
go back to reference 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):2427–38.CrossRefPubMedPubMedCentral 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):2427–38.CrossRefPubMedPubMedCentral
4.
go back to reference Pollack M, Heugel J, Xie H, et al. An international comparison of current strategies to prevent herpesvirus and fungal infections in hematopoietic cell transplant recipients. Biol Blood Marrow Transplant. 2011;17(5):664–73.CrossRefPubMed Pollack M, Heugel J, Xie H, et al. An international comparison of current strategies to prevent herpesvirus and fungal infections in hematopoietic cell transplant recipients. Biol Blood Marrow Transplant. 2011;17(5):664–73.CrossRefPubMed
5.
go back to reference Boeckh M, Gooley TA, Myerson D, Cunningham T, Schoch G, Bowden RA. Cytomegalovirus pp65 antigenemia-guided early treatment with ganciclovir versus ganciclovir at engraftment after allogeneic marrow transplantation: a randomized double-blind study. Blood. 1996;88(10):4063–71.PubMed Boeckh M, Gooley TA, Myerson D, Cunningham T, Schoch G, Bowden RA. Cytomegalovirus pp65 antigenemia-guided early treatment with ganciclovir versus ganciclovir at engraftment after allogeneic marrow transplantation: a randomized double-blind study. Blood. 1996;88(10):4063–71.PubMed
6.
go back to reference Goodrich JM, Bowden RA, Fisher L, Keller C, Schoch G, Meyers JD. Ganciclovir prophylaxis to prevent cytomegalovirus disease after allogeneic marrow transplant. Ann Intern Med. 1993;118(3):173–8.CrossRefPubMed Goodrich JM, Bowden RA, Fisher L, Keller C, Schoch G, Meyers JD. Ganciclovir prophylaxis to prevent cytomegalovirus disease after allogeneic marrow transplant. Ann Intern Med. 1993;118(3):173–8.CrossRefPubMed
7.
go back to reference Winston DJ, Ho WG, Bartoni K, et al. Ganciclovir prophylaxis of cytomegalovirus infection and disease in allogeneic bone marrow transplant recipients. Results of a placebo-controlled, double-blind trial. Ann Intern Med. 1993;118(3):179–84.CrossRefPubMed Winston DJ, Ho WG, Bartoni K, et al. Ganciclovir prophylaxis of cytomegalovirus infection and disease in allogeneic bone marrow transplant recipients. Results of a placebo-controlled, double-blind trial. Ann Intern Med. 1993;118(3):179–84.CrossRefPubMed
8.
go back to reference Reusser P, Gambertoglio JG, Lilleby K, Meyers JD. Phase I-II trial of foscarnet for prevention of cytomegalovirus infection in autologous and allogeneic marrow transplant recipients. J Infect Dis. 1992;166(3):473–9.CrossRefPubMed Reusser P, Gambertoglio JG, Lilleby K, Meyers JD. Phase I-II trial of foscarnet for prevention of cytomegalovirus infection in autologous and allogeneic marrow transplant recipients. J Infect Dis. 1992;166(3):473–9.CrossRefPubMed
9.
go back to reference 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):284–92.CrossRefPubMed 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):284–92.CrossRefPubMed
10.
go back to reference Marty FM, Winston DJ, Rowley SD, et al. CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. N Engl J Med. 2013;369(13):1227–36.CrossRefPubMed Marty FM, Winston DJ, Rowley SD, et al. CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. N Engl J Med. 2013;369(13):1227–36.CrossRefPubMed
11.
go back to reference Chemaly RF, Ullmann AJ, Stoelben S, et al. Letermovir for cytomegalovirus prophylaxis in hematopoietic-cell transplantation. N Engl J Med. 2014;370(19):1781–9.CrossRefPubMed Chemaly RF, Ullmann AJ, Stoelben S, et al. Letermovir for cytomegalovirus prophylaxis in hematopoietic-cell transplantation. N Engl J Med. 2014;370(19):1781–9.CrossRefPubMed
12.
go back to reference Kharfan-Dabaja MA, Boeckh M, Wilck MB, et al. A novel therapeutic cytomegalovirus DNA vaccine in allogeneic haemopoietic stem-cell transplantation: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Infect Dis. 2012;12(4):290–9.CrossRefPubMed Kharfan-Dabaja MA, Boeckh M, Wilck MB, et al. A novel therapeutic cytomegalovirus DNA vaccine in allogeneic haemopoietic stem-cell transplantation: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Infect Dis. 2012;12(4):290–9.CrossRefPubMed
13.
go back to reference Nakamura R, La Rosa C, Longmate J, et al. Viraemia, immunogenicity, and survival outcomes of cytomegalovirus chimeric epitope vaccine supplemented with PF03512676 (CMVPepVax) in allogeneic haemopoietic stem-cell transplantation: randomised phase 1b trial. Lancet Haematol. 2016;3(2):e87–98.CrossRefPubMed Nakamura R, La Rosa C, Longmate J, et al. Viraemia, immunogenicity, and survival outcomes of cytomegalovirus chimeric epitope vaccine supplemented with PF03512676 (CMVPepVax) in allogeneic haemopoietic stem-cell transplantation: randomised phase 1b trial. Lancet Haematol. 2016;3(2):e87–98.CrossRefPubMed
14.
go back to reference Ljungman PT, Chemaly RF, Maertens JA, et al.: A Phase III Randomized, Double-Blind, Placebo-Controlled Trial of Letermovir (LET) for Prevention of Cytomegalovirus (CMV) Infection in Adult CMV-Seropositive Recipients of Allogeneic Hematopoietic Cell Transplantation (HCT). 43rd Annual Meeting of the European Blood and Marrow Transplantation Group, Marseille, March 25–28, 2017, 2017. Ljungman PT, Chemaly RF, Maertens JA, et al.: A Phase III Randomized, Double-Blind, Placebo-Controlled Trial of Letermovir (LET) for Prevention of Cytomegalovirus (CMV) Infection in Adult CMV-Seropositive Recipients of Allogeneic Hematopoietic Cell Transplantation (HCT). 43rd Annual Meeting of the European Blood and Marrow Transplantation Group, Marseille, March 25–28, 2017, 2017.
15.
go back to reference Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11(12):945–56.CrossRefPubMed Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11(12):945–56.CrossRefPubMed
16.
go back to reference Glucksberg H, Storb R, Fefer A, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HLA-matched sibling donors. Transplantation. 1974;18(4):295–304.CrossRefPubMed Glucksberg H, Storb R, Fefer A, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HLA-matched sibling donors. Transplantation. 1974;18(4):295–304.CrossRefPubMed
17.
go back to reference Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15(6):825–8.PubMed Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15(6):825–8.PubMed
18.
go back to reference Transplantation ESfBaM: MED-AB FORMS MANUAL: A guide to the completion of the EBMT HSCT Med-AB forms. vol 2015, 2010. Transplantation ESfBaM: MED-AB FORMS MANUAL: A guide to the completion of the EBMT HSCT Med-AB forms. vol 2015, 2010.
19.
go back to reference Ljungman P, Griffiths P, Paya C. Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis. 2002;34(8):1094–7.CrossRefPubMed Ljungman P, Griffiths P, Paya C. Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis. 2002;34(8):1094–7.CrossRefPubMed
20.
go back to reference 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(4):227–40.CrossRefPubMed 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(4):227–40.CrossRefPubMed
21.
go back to reference Zaia J, Baden L, Boeckh M, et al. Viral disease prevention after hematopoietic cell transplantation. Bone Marrow Transplant. 2009;44:471–82.CrossRefPubMed Zaia J, Baden L, Boeckh M, et al. Viral disease prevention after hematopoietic cell transplantation. Bone Marrow Transplant. 2009;44:471–82.CrossRefPubMed
22.
go back to reference Khera N, Emmert A, Storer B, Sandmaier B, Alyea E, Lee S. Costs of allogeneic hematopoietic cell transplantation using reduced intensity conditioning regimens. Oncologist. 2014;19:639–44.CrossRefPubMedPubMedCentral Khera N, Emmert A, Storer B, Sandmaier B, Alyea E, Lee S. Costs of allogeneic hematopoietic cell transplantation using reduced intensity conditioning regimens. Oncologist. 2014;19:639–44.CrossRefPubMedPubMedCentral
23.
go back to reference Lee SJ, Klar N, Weeks JC, Antin JH. Predicting costs of stem-cell transplantation. J Clin Oncol. 2000;18(1):64–71.CrossRefPubMed Lee SJ, Klar N, Weeks JC, Antin JH. Predicting costs of stem-cell transplantation. J Clin Oncol. 2000;18(1):64–71.CrossRefPubMed
24.
go back to reference Saito AM, Cutler C, Zahrieh D, et al. Costs of allogeneic hematopoietic cell transplantation with high-dose regimens. Biol Blood Marrow Transplant. 2008;14(2):197–207.CrossRefPubMedPubMedCentral Saito AM, Cutler C, Zahrieh D, et al. Costs of allogeneic hematopoietic cell transplantation with high-dose regimens. Biol Blood Marrow Transplant. 2008;14(2):197–207.CrossRefPubMedPubMedCentral
25.
go back to reference Saito AM, Zahrieh D, Cutler C, et al. Lower costs associated with hematopoietic cell transplantation using reduced intensity vs high-dose regimens for hematological malignancy. Bone Marrow Transplant. 2007;40(3):209–17.CrossRefPubMed Saito AM, Zahrieh D, Cutler C, et al. Lower costs associated with hematopoietic cell transplantation using reduced intensity vs high-dose regimens for hematological malignancy. Bone Marrow Transplant. 2007;40(3):209–17.CrossRefPubMed
26.
go back to reference van Agthoven M, Groot MT, Verdonck LF, et al. Cost analysis of HLA-identical sibling and voluntary unrelated allogeneic bone marrow and peripheral blood stem cell transplantation in adults with acute myelocytic leukaemia or acute lymphoblastic leukaemia. Bone Marrow Transplant. 2002;30(4):243–51.CrossRefPubMed van Agthoven M, Groot MT, Verdonck LF, et al. Cost analysis of HLA-identical sibling and voluntary unrelated allogeneic bone marrow and peripheral blood stem cell transplantation in adults with acute myelocytic leukaemia or acute lymphoblastic leukaemia. Bone Marrow Transplant. 2002;30(4):243–51.CrossRefPubMed
27.
go back to reference Esperou H, Brunot A, Roudot-Thoraval F, et al. Predicting the costs of allogeneic sibling stem-cell transplantation: results from a prospective multicenter. French study Transplantation. 2004;77(12):1854–8.PubMed Esperou H, Brunot A, Roudot-Thoraval F, et al. Predicting the costs of allogeneic sibling stem-cell transplantation: results from a prospective multicenter. French study Transplantation. 2004;77(12):1854–8.PubMed
28.
go back to reference Griffiths RI, Bass EB, Powe NR, Anderson GF, Goodman S, Wingard JR. Factors influencing third party payer costs for allogeneic BMT. Bone Marrow Transplant. 1993;12(1):43–8.PubMed Griffiths RI, Bass EB, Powe NR, Anderson GF, Goodman S, Wingard JR. Factors influencing third party payer costs for allogeneic BMT. Bone Marrow Transplant. 1993;12(1):43–8.PubMed
29.
go back to reference Jain NA, Lu K, Ito S, et al. The clinical and financial burden of pre-emptive management of cytomegalovirus disease after allogeneic stem cell transplantation-implications for preventative treatment approaches. Cytotherapy. 2014;16(7):927–33.CrossRefPubMedPubMedCentral Jain NA, Lu K, Ito S, et al. The clinical and financial burden of pre-emptive management of cytomegalovirus disease after allogeneic stem cell transplantation-implications for preventative treatment approaches. Cytotherapy. 2014;16(7):927–33.CrossRefPubMedPubMedCentral
30.
go back to reference Broers AE, van Der Holt R, van Esser JW, et al. Increased transplant-related morbidity and mortality in CMV-seropositive patients despite highly effective prevention of CMV disease after allogeneic T-cell-depleted stem cell transplantation. Blood. 2000;95(7):2240–5.PubMed Broers AE, van Der Holt R, van Esser JW, et al. Increased transplant-related morbidity and mortality in CMV-seropositive patients despite highly effective prevention of CMV disease after allogeneic T-cell-depleted stem cell transplantation. Blood. 2000;95(7):2240–5.PubMed
31.
go back to reference Bontant T, Sedlacek P, Balduzzi A, et al. Survey of CMV management in pediatric allogeneic HSCT programs, on behalf of the inborn errors, infectious diseases and pediatric diseases working parties of EBMT. Bone Marrow Transplant. 2014;49(2):276–9.CrossRefPubMed Bontant T, Sedlacek P, Balduzzi A, et al. Survey of CMV management in pediatric allogeneic HSCT programs, on behalf of the inborn errors, infectious diseases and pediatric diseases working parties of EBMT. Bone Marrow Transplant. 2014;49(2):276–9.CrossRefPubMed
32.
go back to reference Schelfhout J, Brown H, House J. Cost of hematopoietic stem cell transplant and cytomegalovirus-related complications in a large inpatient claims database. California: Infectious Diseases Week San Diego; 2017, October. p. 4–8. Schelfhout J, Brown H, House J. Cost of hematopoietic stem cell transplant and cytomegalovirus-related complications in a large inpatient claims database. California: Infectious Diseases Week San Diego; 2017, October. p. 4–8.
33.
go back to reference 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):1–10.CrossRefPubMedPubMedCentral 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):1–10.CrossRefPubMedPubMedCentral
34.
go back to reference Saret CJ, Winn AN, Shah G, et al. Value of innovation in hematologic malignancies: a systematic review of published cost-effectiveness analyses. Blood. 2015;125(12):1866–9.CrossRefPubMedPubMedCentral Saret CJ, Winn AN, Shah G, et al. Value of innovation in hematologic malignancies: a systematic review of published cost-effectiveness analyses. Blood. 2015;125(12):1866–9.CrossRefPubMedPubMedCentral
Metadata
Title
Economic burden of preemptive treatment of CMV infection after allogeneic stem cell transplantation: a retrospective study of 208 consecutive patients
Authors
Christine Robin
François Hémery
Christel Dindorf
Julien Thillard
Ludovic Cabanne
Rabah Redjoul
Florence Beckerich
Christophe Rodriguez
Cécile Pautas
Andrea Toma
Sébastien Maury
Isabelle Durand-Zaleski
Catherine Cordonnier
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2017
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-017-2854-2

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