Cytomegalovirus infection and rehospitalization rates after allogeneic hematopoietic stem cell and solid organ transplantation: a retrospective cohort study using German claims data.
Allogeneic hematopoietic stem cell transplantation
Claims data
Cytomegalovirus
Solid organ transplantation
Journal
Infection
ISSN: 1439-0973
Titre abrégé: Infection
Pays: Germany
ID NLM: 0365307
Informations de publication
Date de publication:
Dec 2022
Dec 2022
Historique:
received:
24
01
2022
accepted:
03
05
2022
pubmed:
29
5
2022
medline:
1
12
2022
entrez:
28
5
2022
Statut:
ppublish
Résumé
This study aimed to describe the cytomegalovirus (CMV) infection rate, rehospitalizations, and comorbidities following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and solid organ transplantation (SOT). Patients who received allo-HSCT or SOT in 01/07/2015-30/06/2018 were identified using anonymized German claims data. The transplantation-related hospital admission date was defined as the index date, and patients were followed for up to 12 months (or death, first event relevant). The frequency of CMV infections (confirmed outpatient/inpatient diagnoses, ICD-10-GM codes: B25.-/B27.1) and the rate, number, and duration of all-cause rehospitalizations in the follow-up period were evaluated. A total of 226 allo-HSCT and 250 SOT patients were identified (mean age 52.8 years, 38.9% female). During the 12 months after transplantation, 29.2% of allo-HSCT patients and 16.8% of SOT patients received a CMV diagnosis. The majority of these diagnoses were given during the initial hospitalization or within the following 3 months. Across transplantation types, CMV patients had more hospital readmission days per patient-year (allo-HSCT 93.3 vs. 49.4, p = 0.001; SOT 42.0 vs. 20.7, p = 0.005), with a longer mean duration of readmissions (allo-HSCT 22.4 vs. 15.4 days, p < 0.001; SOT 11.6 vs. 7.5 days, p = 0.003). Comorbidity burden in transplantation patients was substantial, with several diagnoses being significantly more common among patients with CMV vs. non-CMV. One-year mortality did not differ significantly between patients with/without CMV. Burden of transplant recipients with CMV in terms of rehospitalizations and comorbidities is substantial, highlighting the need for improved CMV prevention and treatment.
Identifiants
pubmed: 35633464
doi: 10.1007/s15010-022-01847-2
pii: 10.1007/s15010-022-01847-2
pmc: PMC9705421
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1543-1555Informations de copyright
© 2022. The Author(s).
Références
Lachmann R, Loenenbach A, Waterboer T, Brenner N, Pawlita M, Michel A, et al. Cytomegalovirus (CMV) seroprevalence in the adult population of Germany. PLoS One. 2018;13: e0200267. https://doi.org/10.1371/journal.pone.0200267 .
doi: 10.1371/journal.pone.0200267
pubmed: 30044826
pmcid: 6059406
Staras SAS, Dollard SC, Radford KW, Flanders WD, Pass RF, Cannon MJ. Seroprevalence of cytomegalovirus infection in the United States, 1988–1994. Clin Infect Dis. 2006;43:1143–51. https://doi.org/10.1086/508173 .
doi: 10.1086/508173
pubmed: 17029132
Zuhair M, Smit GSA, Wallis G, Jabbar F, Smith C, Devleesschauwer B, et al. Estimation of the worldwide seroprevalence of cytomegalovirus: a systematic review and meta-analysis. Rev Med Virol. 2019;29:e2034. https://doi.org/10.1002/rmv.2034 .
doi: 10.1002/rmv.2034
pubmed: 30706584
Gandhi MK, Khanna R. Human cytomegalovirus: clinical aspects, immune regulation, and emerging treatments. Lancet Infect Dis. 2004;4:725–38. https://doi.org/10.1016/s1473-3099(04)01202-2 .
doi: 10.1016/s1473-3099(04)01202-2
pubmed: 15567122
Haidar G, Boeckh M, Singh N. Cytomegalovirus infection in solid organ and hematopoietic cell transplantation: state of the evidence. J Infect Dis. 2020;221:S23–31. https://doi.org/10.1093/infdis/jiz454 .
doi: 10.1093/infdis/jiz454
pubmed: 32134486
pmcid: 7057778
Ljungman P, Boeckh M, Hirsch HH, Josephson F, Lundgren J, Nichols G, et al. Definitions of cytomegalovirus infection and disease in transplant patients for use in clinical trials. Clin Infect Dis. 2017;64:87–91. https://doi.org/10.1093/cid/ciw668 .
doi: 10.1093/cid/ciw668
pubmed: 27682069
Gesellschaft für Virologie (GfV e.V.) & Deutsche Vereinigung zur Bekämpfung der Viruskrankheiten (DVV e.V.). Virusinfektionen bei organ- und allogen stammzell-transplantierten: Diagnostik, prävention und therapie - S2k-Leitlinie AWMF registernummer 093–002. AWMF online; 2019. https://www.awmf.org/uploads/tx_szleitlinien/093-002l_S2k_Virusinfektionen-Organtransplantierte-alloge-Stammzell-Transplantierten-Diagnostik-Praevention-Therapie__2019-06.pdf
Avery RK, Silveira FP, Benedict K, Cleveland AA, Kauffman CA, Schuster MG, et al. Cytomegalovirus infections in lung and hematopoietic cell transplant recipients in the organ transplant infection prevention and detection study: a multi-year, multicenter prospective cohort study. Transpl Infect Dis. 2018;20: e12877. https://doi.org/10.1111/tid.12877 .
doi: 10.1111/tid.12877
pubmed: 29512935
pmcid: 5989001
Robin C, Hémery F, Dindorf C, Thillard J, Cabanne L, Redjoul R, et al. Economic burden of preemptive treatment of CMV infection after allogeneic stem cell transplantation: a retrospective study of 208 consecutive patients. BMC Infect Dis. 2017;17:747. https://doi.org/10.1186/s12879-017-2854-2 .
doi: 10.1186/s12879-017-2854-2
pubmed: 29207952
pmcid: 5717816
Schelfhout J, Bonafede M, Cappell K, Cole AL, Manjelievskaia J, Raval AD. Impact of cytomegalovirus complications on resource utilization and costs following hematopoietic stem cell transplant. Curr Med Res Opin. 2020;36:33–41. https://doi.org/10.1080/03007995.2019.1664826 .
doi: 10.1080/03007995.2019.1664826
pubmed: 31490093
Ramanan P, Razonable RR. Cytomegalovirus infections in solid organ transplantation: a review. Infect Chemother. 2013;45:260–71.
doi: 10.3947/ic.2013.45.3.260
pubmed: 24396627
pmcid: 3848521
Harvala H, Stewart C, Muller K, Burns S, Marson L, MacGilchrist A, et al. High risk of cytomegalovirus infection following solid organ transplantation despite prophylactic therapy. J Med Virol. 2013;85:893–8. https://doi.org/10.1002/jmv.23539 .
doi: 10.1002/jmv.23539
pubmed: 23508914
Manuel O, Kralidis G, Mueller NJ, Hirsch HH, Garzoni C, van Delden C, et al. Impact of antiviral preventive strategies on the incidence and outcomes of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant. 2013;13:2402–10. https://doi.org/10.1111/ajt.12388 .
doi: 10.1111/ajt.12388
pubmed: 23914796
Cervera C, Pineda M, Linares L, Marcos MA, Esteva C, Antón A, et al. Impact of valganciclovir prophylaxis on the development of severe late-cytomegalovirus disease in high-risk solid organ transplant recipients. Transplant Proc. 2007;39:2228–30. https://doi.org/10.1016/j.transproceed.2007.07.039 .
doi: 10.1016/j.transproceed.2007.07.039
pubmed: 17889146
Linares L, Sanclemente G, Cervera C, Hoyo I, Cofán F, Ricart MJ, et al. Influence of cytomegalovirus disease in outcome of solid organ transplant patients. Transplant Proc. 2011;43:2145–8. https://doi.org/10.1016/j.transproceed.2011.05.007 .
doi: 10.1016/j.transproceed.2011.05.007
pubmed: 21839217
Helanterä I, Schachtner T, Hinrichs C, Salmela K, Kyllönen L, Koskinen P, et al. Current characteristics and outcome of cytomegalovirus infections after kidney transplantation. Transpl Infect Dis. 2014;16:568–77. https://doi.org/10.1111/tid.12247 .
doi: 10.1111/tid.12247
pubmed: 24966022
Nagai S, Mangus RS, Anderson E, Ekser B, Kubal CA, Fridell JA, et al. Cytomegalovirus infection after intestinal/multivisceral transplantation: a single-center experience with 210 cases. Transplantation. 2016;100:451–60. https://doi.org/10.1097/tp.0000000000000832 .
doi: 10.1097/tp.0000000000000832
pubmed: 26247555
Razonable RR, Humar A, The ASTIDCoP. Cytomegalovirus in solid organ transplantation. Am J Transplant. 2013;13:93–106. https://doi.org/10.1111/ajt.12103 .
doi: 10.1111/ajt.12103
pubmed: 23465003
Stern A, Papanicolaou GA. CMV prevention and treatment in transplantation: what’s new in 2019. Curr Infect Dis Rep. 2019;21:45. https://doi.org/10.1007/s11908-019-0699-0 .
doi: 10.1007/s11908-019-0699-0
pubmed: 31732823
pmcid: 8142836
Stern M, Hirsch H, Cusini A, van Delden C, Manuel O, Meylan P, et al. Cytomegalovirus serology and replication remain associated with solid organ graft rejection and graft loss in the era of prophylactic treatment. Transplantation. 2014;98:1013–8. https://doi.org/10.1097/tp.0000000000000160 .
doi: 10.1097/tp.0000000000000160
pubmed: 24837540
Kotton CN, Kumar D, Caliendo AM, Huprikar S, Chou S, Danziger-Isakov L, et al. The third international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation. Transplantation. 2018;102:900–31. https://doi.org/10.1097/tp.0000000000002191 .
doi: 10.1097/tp.0000000000002191
pubmed: 29596116
Ariza-Heredia EJ, Nesher L, Chemaly RF. Cytomegalovirus diseases after hematopoietic stem cell transplantation: a mini-review. Cancer Lett. 2014;342:1–8. https://doi.org/10.1016/j.canlet.2013.09.004 .
doi: 10.1016/j.canlet.2013.09.004
pubmed: 24041869
Cantoni N, Hirsch HH, Khanna N, Gerull S, Buser A, Bucher C, et al. Evidence for a bidirectional relationship between cytomegalovirus replication and acute graft-versus-host disease. Biol Blood Marrow Transplant. 2010;16:1309–14. https://doi.org/10.1016/j.bbmt.2010.03.020 .
doi: 10.1016/j.bbmt.2010.03.020
pubmed: 20353832
Bhutani D, Dyson G, Manasa R, Deol A, Ratanatharathorn V, Ayash L, et al. Incidence, risk factors, and outcome of cytomegalovirus viremia and gastroenteritis in patients with gastrointestinal graft-versus-host disease. Biol Blood Marrow Transplant. 2015;21:159–64. https://doi.org/10.1016/j.bbmt.2014.10.004 .
doi: 10.1016/j.bbmt.2014.10.004
pubmed: 25445637
Witzke O, Nitschke M, Bartels M, Wolters H, Wolf G, Reinke P, et al. Valganciclovir prophylaxis versus preemptive therapy in cytomegalovirus-positive renal allograft recipients: long-term results after 7 years of a randomized clinical trial. Transplantation. 2018;102:876–82. https://doi.org/10.1097/tp.0000000000002024 .
doi: 10.1097/tp.0000000000002024
pubmed: 29166336
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;12:1481–91. https://doi.org/10.2147/idr.S180908 .
doi: 10.2147/idr.S180908
pubmed: 31239725
pmcid: 6556539
Danziger-Isakov L, Mark BG. Hematologic complications of anti-CMV therapy in solid organ transplant recipients. Clin Transplant. 2009;23:295–304. https://doi.org/10.1111/j.1399-0012.2008.00942.x .
doi: 10.1111/j.1399-0012.2008.00942.x
pubmed: 19191800
Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47:1245–51. https://doi.org/10.1016/0895-4356(94)90129-5 .
doi: 10.1016/0895-4356(94)90129-5
pubmed: 7722560
Deutsche stiftung organtransplantation. Jahresbericht: Organspende und transplantation in Deutschland 2020. 2020. https://dso.de/SiteCollectionDocuments/DSO-Jahresbericht%202020.pdf
Schelfhout J, Brown H, House JA, Raval AD. Cytomegalovirus infection and associated hospitalization and costs among individuals undergoing allogeneic hematopoietic stem cell transplant. Curr Med Res Opin. 2020;36:43–50. https://doi.org/10.1080/03007995.2019.1664827 .
doi: 10.1080/03007995.2019.1664827
pubmed: 31490097
Hakimi Z, Aballéa S, Ferchichi S, Scharn M, Odeyemi IA, Toumi M, et al. Burden of cytomegalovirus disease in solid organ transplant recipients: a national matched cohort study in an inpatient setting. Transpl Infect Dis. 2017. https://doi.org/10.1111/tid.12732 .
doi: 10.1111/tid.12732
pubmed: 28599091
Chemaly RF, El Haddad L, Winston DJ, Rowley SD, Mulane KM, Chandrasekar P, et al. Cytomegalovirus (CMV) cell-mediated immunity and CMV infection after allogeneic hematopoietic cell transplantation: the REACT study. Clin Infect Dis. 2020;71:2365–74. https://doi.org/10.1093/cid/ciz1210 .
doi: 10.1093/cid/ciz1210
pubmed: 32076709
pmcid: 7713694
Wei L, Chen SJ, Huang SF, Chan YJ, Wang FD, Chen HP. Clinical significance of human cytomegalovirus viruria and the effect of antiviral therapy in hematopoietic stem cell transplant recipients. J Microbiol Immunol Infect. 2019;52:402–8. https://doi.org/10.1016/j.jmii.2017.08.019 .
doi: 10.1016/j.jmii.2017.08.019
Smedbråten YV, Sagedal S, Leivestad T, Mjøen G, Osnes K, Rollag H, et al. The impact of early cytomegalovirus infection after kidney transplantation on long-term graft and patient survival. Clin Transplant. 2014;28:120–6. https://doi.org/10.1111/ctr.12288 .
doi: 10.1111/ctr.12288
pubmed: 24351078
Sagedal S, Rollag H, Hartmann A. Cytomegalovirus infection in renal transplant recipients is associated with impaired survival irrespective of expected mortality risk. Clin Transplant. 2007;21:309–13. https://doi.org/10.1111/j.1399-0012.2006.00639.x .
doi: 10.1111/j.1399-0012.2006.00639.x
pubmed: 17488378
Falagas ME, Paya C, Ruthazer R, Badley A, Patel R, Wiesner R, et al. Significance of cytomegalovirus for long-term survival after orthotopic liver transplantation: a prospective derivation and validation cohort analysis. Transplantation. 1998;66:1020–8. https://doi.org/10.1097/00007890-199810270-00010 .
doi: 10.1097/00007890-199810270-00010
pubmed: 9808486
Falagas ME, Snydman DR, Griffith J, Ruthazer R, Werner BG. Effect of cytomegalovirus infection status on first-year mortality rates among orthotopic liver transplant recipients. The Boston center for liver transplantation CMVIG study group. Ann Intern Med. 1997;126:275–9. https://doi.org/10.7326/0003-4819-126-4-199702150-00003 .
doi: 10.7326/0003-4819-126-4-199702150-00003
pubmed: 9036799
Au BK, Gooley TA, Armand P, Fang M, Madtes DK, Sorror ML, et al. Reevaluation of the pretransplant assessment of mortality score after allogeneic hematopoietic transplantation. Biol Blood Marrow Transplant. 2015;21:848–54. https://doi.org/10.1016/j.bbmt.2015.01.011 .
doi: 10.1016/j.bbmt.2015.01.011
pubmed: 25644959
pmcid: 4408250
Ljungman P, Brand R, Hoek J, de la Camara R, Cordonnier C, Einsele H, 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;59:473–81. https://doi.org/10.1093/cid/ciu364 .
doi: 10.1093/cid/ciu364
pubmed: 24850801
Desai R, Collett D, Watson CJ, Johnson PJ, Moss P, Neuberger J. Impact of cytomegalovirus on long-term mortality and cancer risk after organ transplantation. Transplantation. 2015;99:1989–94. https://doi.org/10.1097/tp.0000000000000641 .
doi: 10.1097/tp.0000000000000641
pubmed: 25706273
Suarez-Pierre A, Giuliano K, Lui C, Almaguer D, Etchill E, Choi CW, et al. Impact of cytomegalovirus serologic status on heart transplantation. J Card Surg. 2020;35:1431–8. https://doi.org/10.1111/jocs.14588 .
doi: 10.1111/jocs.14588
pubmed: 32362003
Mabilangan C, Preiksaitis J, Cervera C. Impact of donor and recipient cytomegalovirus serology on long-term survival of lung transplant recipients. Transpl Infect Dis. 2018;20: e12964. https://doi.org/10.1111/tid.12964 .
doi: 10.1111/tid.12964
pubmed: 29981174
Mabilangan C, Preiksaitis JK, Cervera C. Impact of donor and recipient cytomegalovirus serology on long-term survival of heart transplant recipients. Transpl Infect Dis. 2019;21: e13015. https://doi.org/10.1111/tid.13015 .
doi: 10.1111/tid.13015
pubmed: 30358023
Serrano-Alonso M, Guillen-Grima F, Martin-Moreno P, Rabago G, Manrique J, Garcia-Del-Barrio M, et al. Reduction in mortality associated with secondary cytomegalovirus prophylaxis after solid organ transplantation. Transpl Infect Dis. 2018;20: e12873. https://doi.org/10.1111/tid.12873 .
doi: 10.1111/tid.12873
pubmed: 29512280
Ljungman P, Schmitt M, Marty FM, Maertens J, Chemaly RF, Kartsonis NA, et al. A mortality analysis of letermovir prophylaxis for cytomegalovirus (CMV) in CMV-seropositive recipients of allogeneic hematopoietic cell transplantation. Clin Infect Dis. 2020;70:1525–33. https://doi.org/10.1093/cid/ciz490 .
doi: 10.1093/cid/ciz490
pubmed: 31179485
Mori Y, Jinnouchi F, Takenaka K, Aoki T, Kuriyama T, Kadowaki M, et al. Efficacy of prophylactic letermovir for cytomegalovirus reactivation in hematopoietic cell transplantation: a multicenter real-world data. Bone Marrow Transplant. 2021;56:853–62. https://doi.org/10.1038/s41409-020-01082-z .
doi: 10.1038/s41409-020-01082-z
pubmed: 33139867
Committee for medicinal products for human Use (CHMP). Clinical investigation of immunosuppressants for solid organ transplantation. European medicines agency; 2009. https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-clinical-investigation-immunosuppressants-solid-organ-transplantation_en.pdf
Berger SP, Sommerer C, Witzke O, Tedesco H, Chadban S, Mulgaonkar S, et al. Two-year outcomes in de novo renal transplant recipients receiving everolimus-facilitated calcineurin inhibitor reduction regimen from the TRANSFORM study. Am J Transplant. 2019;19:3018–34. https://doi.org/10.1111/ajt.15480 .
doi: 10.1111/ajt.15480
pubmed: 31152476
Masouridi-Levrat S, Simonetta F, Chalandon Y. Immunological basis of bone marrow failure after allogeneic hematopoietic stem cell transplantation. Front Immunol. 2016. https://doi.org/10.3389/fimmu.2016.00362 .
doi: 10.3389/fimmu.2016.00362
pubmed: 27695456
pmcid: 5025429
Wilkinson AH, Danovitch G, Mischel M. Fluid and electrolyte disorders associated with orthotopic liver transplantation. Springer; 1990. https://doi.org/10.1007/978-1-4613-1491-2_1
doi: 10.1007/978-1-4613-1491-2_1
Pochineni V, Rondon-Berrios H. Electrolyte and acid-base disorders in the renal transplant recipient. Front Med (Lausanne). 2018;5:261. https://doi.org/10.3389/fmed.2018.00261 .
doi: 10.3389/fmed.2018.00261
pubmed: 30333977
Rondón G, Saliba RM, Chen J, Ledesma C, Alousi AM, Oran B, et al. Impact of fluid overload as new toxicity category on hematopoietic stem cell transplantation outcomes. Biol Blood Marrow Transplant. 2017;23:2166–71. https://doi.org/10.1016/j.bbmt.2017.08.021 .
doi: 10.1016/j.bbmt.2017.08.021
pubmed: 28844946
pmcid: 5889108
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: e13866. https://doi.org/10.1111/ctr.13866 .
doi: 10.1111/ctr.13866
pubmed: 32242979
Derigs P, Radujkovic A, Schubert ML, Schnitzler P, Schöning T, Müller-Tidow C, et al. Letermovir prophylaxis is effective in preventing cytomegalovirus reactivation after allogeneic hematopoietic cell transplantation: single-center real-world data. Ann Hematol. 2021;100:2087–93. https://doi.org/10.1007/s00277-020-04362-2 .
doi: 10.1007/s00277-020-04362-2
pubmed: 33270162
Imlay HN, Kaul DR. Letermovir and maribavir for the treatment and prevention of cytomegalovirus infection in solid organ and stem cell transplant recipients. Clin Infect Dis. 2021;73:156–60. https://doi.org/10.1093/cid/ciaa1713 .
doi: 10.1093/cid/ciaa1713
pubmed: 33197929
Maertens J, Cordonnier C, Jaksch P, Poiré X, Uknis M, Wu J, et al. Maribavir for preemptive treatment of cytomegalovirus reactivation. N Engl J Med. 2019;381:1136–47. https://doi.org/10.1056/NEJMoa1714656 .
doi: 10.1056/NEJMoa1714656
pubmed: 31532960
Wang LH, Peck RW, Yin Y, Allanson J, Wiggs R, Wire MB. Phase I safety and pharmacokinetic trials of 1263W94, a novel oral anti-human cytomegalovirus agent, in healthy and human immunodeficiency virus-infected subjects. Antimicrob Agents Chemother. 2003;47:1334–42. https://doi.org/10.1128/aac.47.4.1334-1342.2003 .
doi: 10.1128/aac.47.4.1334-1342.2003
pubmed: 12654667
pmcid: 152490
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. Clinical Infect Dis. 2021. https://doi.org/10.1093/cid/ciab988 .
doi: 10.1093/cid/ciab988