Цитомегаловирусная инфекция при трансплантации аллогенных гемопоэтических стволовых клеток: основное клиническое значение и определения

Цитомегаловирусная инфекция является лидирующей причиной смертности у пациентов после трансплантации аллогенных гемопоэтических стволовых клеток, особенно в ранние сроки.

Одними из наиболее значимых факторов риска развития цитомегаловирусной инфекции у реципиентов аллогенных гемопоэтических стволовых клеток являются цитомегаловирусная серопозитивность донора и (или) реципиента, а также недостаточная и (или) отсроченная реконституция цитомегаловирусных специфических CD4+ и CD8+ Т-лимфоцитов после трансплантации аллогенных гемопоэтических стволовых клеток.

Спектр клинических проявлений разнообразен: как от бессимптомного течения, так и до развития цитомегаловирусной болезни с вовлечением органов-мишеней, что случается в 10–40% случаев. На сегодняшний день доступны публикации, подтверждающие как неблагоприятное, так и «положительное» влияние цитомегаловируса на отдаленные результаты у пациентов после трансплантации аллогенных гемопоэтических стволовых клеток. Острая и хроническая реакция «трансплантат против хозяина» могут также являться факторами риска развития цитомегаловирусной инфекции. В некоторых работах описано влияние цитомегаловирусной инфекции на развитие несостоятельности трансплантата. Однако известен и «противолейкемический эффект» цитомегаловирусной инфекции, когда эпизод цитомегаловирусной инфекции снижает вероятность развития рецидива у пациентов с острым миелоидным лейкозом, хроническим миелолейкозом.

Несмотря на внедрение стратегий профилактической, превентивной и таргетной терапии цитомегаловирусной инфекции, она до сих пор ухудшает посттрансплантационные показатели.

Целью этого обзора стала систематизация современных понятий, применяемых при оценке и лечении цитомегаловирусной инфекции у пациентов после трансплантации аллогенных гемопоэтических стволовых клеток.

1. 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(12):1958-1967. PMID: 25139217 https://doi.org/10.1016/j.bbmt.2014.08.010

2. Teira P, Battiwalla M, Ramana than M, Barrett AJ, Ahn KW, Chen 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. PMID: 26884374 https://doi.org/10.1182/blood-2015-11-679639

3. Sun R-J, Wei Z-J, Liu D-Y, Cao X-Y, Zhang J-P, Xiong M, et al. Efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for 67 pediatric patients with high risk T-cell acute lymphoblastic leukemia (T-ALL). Biol Blood Marrow Trans plant. 2019;25(3):S111–S112. https://doi.org/10.1016/J.BBMT.2018.12.387

4. Zuhair M, Smit G, Wallis G, Jab bar F, Smith C, Devleesschauwer B, et al. Estimation of the worldwide seroprevalence of cytomegalovirus: а systematic review and meta-analysis. Rev Med Virol. 2019;29(3):e2034. PMID: 30706584 https://doi.org/10.1002/RMV.2034

5. Seo S, Cho Y, Park J. Serologic screening of pregnant Korean women for primary human cytomegalovirus infection using IgG avidity test. Korean J Lab Med. 2009;29(6):557–562. PMID: 20046088 https://doi.org/10.3343/KJLM.2009.29.6.557

6. Boeckh M, Geballe AP. Cytomegalovirus: pathogen, paradigm, and puzzle. J Clin Invest. 2011;121(5):1673–1680. PMID: 21659716 https://doi.org/10.1172/JCI45449

7. Walter EA, Greenberg PD, Gilbert MJ, Finch RJ, Watanabe KS, Thomas ED, et al. Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by trans fer of T-cell clones from the donor. N Engl J Med. 1995;333(16):1038–1044. PMID: 7675046 https://doi.org/10.1056/NEJM199510193331603

8. Boeckh M, Leisenring W, Riddell SR, Bowden RA, Huang M-L, Myerson D, et al. Late cytomegalovirus disease and mortality in recipients of allogeneic hematopoietic stem cell transplants: importance of viral load and T-cell immunity. Blood. 2003;101(2):407–414. PMID: 12393659 https://doi.org/10.1182/BLOOD-2002-03-0993

9. Bhat V, Joshi A, Sarode R, Chavan P. Cytomegalovirus infection in the bone marrow transplant patient. World J Transplant. 2015;5(4):287–291. PMID: 26722656 https://doi.org/10.5500/WJT.V5.I4.287

10. Ljungman P. CMV infections after hematopoietic stem cell transplantation. Bone Marrow Transplant. 2008;42 Suppl 1:S70–72. PMID: 18724309 https://doi.org/10.1038/bmt.2008.120

11. Cho S-Y, Lee D-G, Kim H-J. Cytomegalovirus infections after hematopoietic stem cell transplantation: current status and future immunotherapy. Int J Mol Sci. 2019;20(11):2666. PMID: 31151230 https://doi.org/10.3390/IJMS20112666

12. Mattsson J, Ringd én O, Storb R. Graft failure after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2008;14(1Suppl 1):165–170. PMID: 18162238 https://doi.org/10.1016/J.BBMT.2007.10.025

13. Einsele H, Ljungman P, Boeckh M. How I treat CMV reactivation after allogeneic hematopoietic stem cell transplantation. Blood. 2020;135(19):1619-1629. PMID: 32202631 https://doi.org/10.1182/BLOOD.2019000956

14. Cantoni N, Hirsch HH, Khanna N, Gerull S, Buser A, Bucher C, et al. Evidence for a bidirectional relationship between cytomegalovirus rep lication and acute graft-versus-host disease. Biol Blood Marrow Trans plant. 2010;16(9):1309–1314. PMID: 20353832 https://doi.org/10.1016/J.BBMT.2010.03.020

15. Suessmuth Y, Betz K, Yu A, Bratrude B, Watkins B, Qayed M, et al. Potent interaction between CMV reactiva tion and GVHD: immunologic evidence for blunting of CMV-driven immune reconstitution in the setting of Gvhd. Blood. 2020;136(Suppl 1):50. https://doi.org/10.1182/BLOOD-2020-141856

16. Green ML, Leisenring WM, Xie H, Walter RB, Mielcarek M, Sandmaier BM, et al. CMV reactivation after allogeneic HCT and relapse risk: evidence for early protection in acute myeloid leukemia. Blood. 2013;122(7):1316–1324. PMID: 23744585 https://doi.org/10.1182/BLOOD-2013-02-487074

17. Elmaagacli AH, Steckel N, Koldehoff M, Hegerfeldt Y, Trenschel R, Ditschkowski 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. PMID: 21540462 https://doi.org/10.1182/BLOOD-2010-08-304121

18. 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(1):87–91. PMID: 27682069 https://doi.org/10.1093/cid/ciw668

19. Razonable RR, Inoue N, Pinninti SG, Boppana SB, Lazzarotto T, Gabrielli L, et al. Clinical diagnostic testing for human cytomegalovirus infections. The J Infect Dis. 2020;221(Suppl 1):S74–85. PMID: 32134488 https://doi.org/10.1093/INFDIS/JIZ601

20. Evans P, Soin A, Wreghitt T, Alexander G. Qualitative and semiquantitative polymerase chain reaction testing for cytomegalovirus DNA in serum allows prediction of CMV related disease in liver transplant recipients. J Clin Pathol. 1998;51(12):914–921. PMID: 10070333 https://doi.org/10.1136/JCP.51.12.914

21. Einsele H, Ehninger G, Steidle M, Vallbracht A, Müller F, Schmidt H, et al. Polymerase chain reaction to evaluate antiviral therapy for cytomegalovirus disease. Lancet. 1991;338(8776):1170-1172. PMID: 1682592 https://doi.org/10.1016/0140-6736(91)92032-W

22. Teng CLJ, Wang PN, Chen YC, Ko BS. Cytomegalovirus management after allogeneic hematopoietic stem cell transplantation: а mini-review. J Microbiol Immunol Infect. 2021;54(3):341–348. PMID: 33514495 https://doi.org/10.1016/J.JMII.2021.01.001

23. Breda G, Almeida B, Carstensen S, Bonfim CM, Nogueira MB, Vidal LR, et al. Human cytomegalovirus detection by real-time PCR and pp65-antigen test in hematopoietic stem cell transplant recipients: a challenge in low and middle-income countries. Pathog Glob Health. 2013;107(6):312–319. PMID: 24188241 PMID: 21827433 https://doi.org/10.1179/2047773213Y.0000000114

24. Ross S, Novak Z, Pati S, Boppana S. Overview of the diagnosis of cytomegalovirus infection. Infect Disord Drug Targets. 2011;11(5):466–474. https://doi.org/10.2174/187152611797636703

25. Paya C, Holley K, Wiesner R, Balasubramaniam K, Smith T, Espy M, et al. Early diagnosis of cytomegalovirus hepatitis in liver transplant recipients: role of immunostaining, DNA hybridization and culture of hepatic tissue. Hepatology. 1990;12(1):119–126. PMID: 2165031 https://doi.org/10.1002/HEP.1840120119

26. Chemaly RF, Chou S, Einsele H, Griffiths P, Avery R, Razonable RR, et al. Definitions of resistant and refractory cytomegalovirus infection and disease in transplant recipients for use in clinical trials. Clin Infect Dis. 2019;68(8):1420-1426. PMID: 30137245 https://doi.org/10.1093/CID/CIY696

27. Griffiths P. New vaccines and antiviral drugs for cytomegalovirus. J Clin Virol. 2019;116:58–61. PMID: 31132546 https://doi.org/10.1016/J.JCV.2019.04.007

28. Forte E, Zhang Z, Thorp EB, Hummel M. Cytomegalovirus latency and reactivation: an intricate interplay with the host immune response. Front Cell Infect Microbiol. 2020;10:130. PMID: 32296651 https://doi.org/10.3389/FCIMB.2020.00130

29. 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(4):473–481. https://doi.org/10.1093/CID/CIU364

30. Styczynski J. Who is the patient at risk of CMV recurrence: a review of the current scientific evidence with a focus on hematopoietic cell transplantation. Infect Dis Ther. 2018;7(1):1–16. PMID: 29204910 https://doi.org/10.1007/S40121-017-0180-Z

31. Boeckh M, Ljungman P. How we treat cytomegalovirus in hematopoi etic cell transplant recipients. Blood. 2009;113(23):5711–5719. PMID: 19299333 https://doi.org/10.1182/BLOOD-200810-143560

32. Asano-Mori Y, Kanda Y, Oshima K, Kako S, Shinohara A, Nakasone H, et al. Clinical features of late cytomega lovirus infection after hematopoietic stem cell transplantation. Int J Hematol. 2008;87(3):310–318. PMID: 18320138 https://doi.org/10.1007/S12185-008-0051-1

33. Han SH, Yoo SG, Han K Do, La Y, Kwon DE, Lee KH. The incidence and effect of cytomegalovirus disease on mortality in transplant recipients and general population: real-world nationwide cohort data. Int J Med Sci. 2021;18(14):3333–3341. PMID: 34400903 https://doi.org/10.7150/IJMS.62621

34. Ljungman P, Griffiths P, Paya C. Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis. 2002;34(8):1094–1097. PMID: 11914998 https://doi.org/10.1086/339329

35. Razonable R. Management strategies for cytomegalovirus infection and disease in solid organ transplant recipients. Infect Dis Clin North Am. 2013;27(2):317–342. PMID: 23714343 https://doi.org/10.1016/J.IDC.2013.02.005

36. Dioverti M, Razonable R. Clinical utility of cytomegalovirus viral load in solid organ transplant recipients. Curr Opin Infect Diss. 2015;28(4):317–322. PMID: 26098497 https://doi.org/10.1097/QCO.0000000000000173

37. Bentley S. Bone marrow connective tissue and the haemopoietic microenvironment. Br J Haematol. 1982;50(1):1–6. PMID: 7034766 https://doi.org/10.1111/J.1365-2141.1982.TB01884.X

38. 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(8):e260–e272. PMID: 31153807 https://doi.org/10.1016/S1473-3099(19)30107-0

39. Mainou M, Alahdab F, Tobian AAR, Asi N, Mohammed K, Murad MH, et al. Reducing the risk of transfusion-transmitted cytomegalovirus infection: a systematic review and meta-analysis. Transfusion. 2016;56(6 Pt2):1569–1580. PMID: 26826015 https://doi.org/10.1111/TRF.13478

40. Nichols WG, Price TH, Gooley T, Corey L, Boeckh M. Transfusion-transmitted cytomegalovirus infection after receipt of leukoreduced blood products. Blood. 2003;101(10):4195–4200. PMID: 12531791 https://doi.org/10.1182/BLOOD-2002-10-3143

41. Ljungman P, de la Camara R, Cordonnier C, Einsele H, Engelhard D, Reusser P, 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):227–240. PMID: 18587440 https://doi.org/10.1038/bmt.2008.162

42. Jakharia N, Howard D, Riedel DJ. CMV Infection in hematopoietic stem cell transplantation: prevention and treatment strategies. Curr Treat Options Infect Dis. 2021;13(3):123–140. PMID: 34305463 https://doi.org/10.1007/S40506-021-00253-W

43. Solano C, Gim énez E, Pi ñana JL, Hernández-Boluda JC, Amat P, Vinuesa V, et al. When should preemp tive antiviral therapy for active CMV infection be withdrawn from allogeneic stem cell transplant recipients? Bone Marrow Transplant. 2017;52(10):1448-1451. PMID: 28581458 https://doi.org/10.1038/bmt.2017.109

44. Martín-Gandul C, Pérez-Romero P, Sánchez M, Bernal G, Suárez G, Sobrino M, et al. Determination, validation and standardization of a CMV DNA cut-off value in plasma for preemptive treatment of CMV infection in solid organ transplant recipients at lower risk for CMV infection. J Clin Virol. 2013;56(1):13–18. PMID: 23131346 https://doi.org/10.1016/J.JCV.2012.09.017

45. Green ML, Leisenring W, Stachel D, Pergam SA, Sandmaier BM, Wald A, et al. Efficacy of a viral load-based, riskadapted, preemptive treatment stra tegy for prevention of cytomegalovirus disease after hematopoietic cell transplantation. Biol Blood Marrow Trans plant. 2012;18(11):1687–1699. PMID: 22683614 https://doi.org/10.1016/J.BBMT.2012.05.015

46. Демин М.В., Тихомиров Д.С., Бидерман Б.В., Глинщикова О.А., Дроков М.Ю., Судариков А.Б. и др. Мутации в гене UL97 цитомегаловируса, ассоциированные с устойчивостью к ганцикловиру, у реципиентов аллогенных гемопоэтических стволовых клеток. Клиническая микробиология и антимикробная химиотерапия. 2019;21(4):352–357. https://doi.org/10.36488/CMAC.2019.4.352-357

47. Демин М.В., Тихомиров Д.С., Бидерман Б.В., Глинщикова О.А., Судариков А.Б., Туполева Т.А. и др. Мутации в гене фосфотрансферазы цитомегаловируса, вызывающие устойчивость к ганцикловиру, у пациентов с иммунодефицитом. Вестник гематологии. 2020;16(3):40–41.

48. Papanicolaou GA, Silveira FP, Langston AA, Pereira MR, Avery RK, Uknis M, et al. Maribavir for refractory or resistant cytomegalovirus infections in hematopoietic-cell or solid-organ transplant recipients: a randomized, dose-ranging, double-blind, phase 2 study. Clin Infect Dis. 2019;68(8):1255–1264. PMID: 30329038 https://doi.org/10.1093/CID/CIY706

49. Liu J, Kong J, Chang YJ, Chen H, Chen YH, Han W, et al. Patients with refractory cytomegalovirus (CMV) infection following allogeneic haematopoietic stem cell transplantation are at high risk for CMV disease and nonrelapse mortality. Clin Microbiol Infect. 2015;21(12):1121.e9–1121.e15. PMID: 26093077 https://doi.org/10.1016/J.CMI.2015.06.009

50. Grefte A, Giessen M van der, Son W van, The TH. Circulating cytomegalovirus (CMV)-infected endothelial cells in patients with an active CMV infection. J Infect Dis. 1993;167(2):270–277. PMID: 8380609 https://doi.org/10.1093/INFDIS/167.2.270

51. Cantoni N, Hirsch HH, Khanna N, Gerull S, Buser A, Bucher C, et al. Evidence for a bidirectional relationship between cytomegalovirus rep lication and acute graft-versus-host disease. Biol Blood Marrow Trans plant. 2010;16(9):1309–1314. PMID: 20353832 https://doi.org/10.1016/J.BBMT.2010.03.020

52. Löunnqvist B, Ringdegn O, Ljungman P, Wahren B, Gahrton G. Reduced risk of recurrent leukaemia in bone marrow transplant recipi ents after cytomegalovirus infec tion. Br J Haematol. 1986;63(4):671–679. PMID: 3015193 https://doi.org/10.1111/J.1365-2141.1986.TB07551.X

53. Behrendt C, Rosenthal J, Bolotin E, Nakamura R, Zaia J, Forman S. Donor and recipient CMV serostatus and outcome of pediatric allogeneic HSCT for acute leukemia in the era of CMV-preemptive therapy. Biol Blood Marrow Transplant. 2009;15(1):54–60. PMID: 19135943 https://doi.org/10.1016/J.BBMT.2008.10.023

54. Elmaagacli AH, Steckel N, Koldehoff M, Hegerfeldt Y, Trenschel R, Ditschkowski 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. PMID: 21540462 https://doi.org/10.1182/BLOOD-2010-08-304121

55. Green M, Leisenring W, Xie H, Walter R, Mielcarek M, Sandmaier B, et al. CMV reactivation after allogeneic HCT and relapse risk: evidence for early protection in acute myeloid leukemia. Blood. 2013;122(7):1316–1324. PMID: 23744585 https://doi.org/10.1182/BLOOD-2013-02-487074

56. Ito S, Pophali P, CO W, Koklanaris E, Superata J, Fahle G, et al. CMV reactivation is associated with a lower incidence of relapse after allo-SCT for CML. Bone Marrow Transplant. 2013;48(10):1313-1316. PMID: 23562969 https://doi.org/10.1038/BMT.2013.49

57. Yoon J-H, Lee S, Kim H-J, Jeon Y-W, Lee S-E, Cho B-S, et al. Impact of cytomegalovirus reactivation on relapse and survival in patients with acute leukemia who received allogeneic hematopoietic stem cell transplantation in first remission. Oncotarget. 2016;7(13):17230-17241. PMID: 26883100 https://doi.org/10.18632/ONCOTARGET.7347

58. Elmaagacli AH, Koldehoff M. Cytomegalovirus replication redu ces the relapse incidence in patients with acute myeloid leukemia. Blood. 2016;128(3):456–459. PMID: 27216219 https://doi.org/10.1182/BLOOD-2016-04-713644

59. Cooley S, Weisdorf D, Guethlein L, Klein J, Wang T, Le C, et al. Donor selection for natural killer cell receptor genes leads to superior survival after unrelated transplantation for acute myelogenous leukemia. Blood. 2010;116(14):2411-2419. PMID: 20581313 https://doi.org/10.1182/BLOOD-2010-05-283051

60. Scheper W, van Dorp S, Kersting S, Pietersma F, Lindemans C, Hol S, et al. γδT cells elicited by CMV reactivation after allo-SCT cross-recognize CMV and leukemia. Leukemia. 2013;27(6):1328-1338. PMID: 23277330 https://doi.org/10.1038/LEU.2012.374

61. Zhang Y-L, Zhu Y, Xiao Q, Wang L, Liu L, Luo X-H. Cytomegalovirus infection is associated with AML relapse after allo-HSCT: a meta-analysis of observational studies. Anт Hematol. 2019;98(4):1009–1020. PMID: 30666434 https://doi.org/10.1007/S00277-018-3585-1

62. Solano C, Vázquez L, Giménez E, de la Cámara R, Albert E, Rovira M, et al. Clinical outcomes of allogeneic hematopoietic stem cell transplant recipients developing Cytomegalovirus DNAemia prior to engraftment. Bone Marrow Transplantat. 2021;56(6):1281–1290. PMID: 33319853 https://doi.org/10.1038/s41409-020-01157-x

63. Jeljeli M, Gu érin-El Khourouj V, Porcher R, Fahd M, Leveillé S, Yakouben K, et al. Relationship between cytomegalovirus (CMV) reactivation, CMV-driven immunity, overall immune recovery and graft-versus-leukaemia effect in children. Br J Hhaematol. 2014;166(2):229–239. PMID: 24702221 https://doi.org/10.1111/BJH.12875

64. Jang J, Kim S, Cheong J, Hyun S, Kim Y, Kim Y, et al. Early CMV rep lication and subsequent chronic GVHD have a significant anti-leukemic effect after allogeneic HSCT in acute myeloid leukemia. Ann Hematol. 2015;94(2):275–282. PMID: 25135450 https://doi.org/10.1007/S00277-014-2190-1

65. Ozdemir Z, Civriz Bozdağ S. Graft failure after allogeneic hematopoietic stem cell transplantation. Transfusion and apheresis science. 2018;57(2):163–167. PMID: 29724627 https://doi.org/10.1016/J.TRANSCI.2018.04.014

66. Hutt D. Engraftment, graft failure, and rejection. In: The european blood and marrow transplantation textbook for nurses: under the auspices of EBMT. Cham: Springer; 2018. Ch. 13. https://doi.org/10.1007/978-3-319-50026-3_13

67. Locatelli F, Lucarelli B, Merli P. Current and future approaches to treat graft failure after allogeneic hematopoietic stem cell transplantation. Expert Opin Pharmacother. 2014;15(1):23–36. PMID: 24156789 https://doi.org/10.1517/14656566.2014.852537

68. Solano C, Gim é nez E, Albert E, Mateo E, Gómez M, Goterris R, et al. Preengraftment cytomegalovirus DNAemia in allogeneic hematopoietic stem cell transplant recipients: incidence, risk factors, and clinical outcomes. Bone Marrow Transplantat. 2019;5(1):90–98. PMID: 29899574 https://doi.org/10.1038/s41409-018-0251-0

69. Bunchorntavakul C, Reddy K. Epstein-Barr Virus and cytomegalovirus infections of the liver. Gastroenterology clinics of North America. 2020;49(2):331–346. PMID: 32389366 https://doi.org/10.1016/J.GTC.2020.01.008

70. O’Grady J, Alexander G, Sutherland S, Donaldson P, Harvey F, Port mann B, et al. Cytomegalovirus infection and donor/recipient HLA antigens: interdependent co-factors in patho genesis of vanishing bile-duct syn drome after liver transplantation. Lancet. 1988;2(8606):302–305. https://doi.org/10.1016/S0140-6736(88)92356-2

71. Romero FA, Razonable RR. Infections in liver transplant recipients. World J Hepatol. 2011;3(4):83–94. PMID: 21603030 https://doi.org/10.4254/WJH.V3.I4.83

72. Gatault P, Halimi J, Forconi C, Thibault G, Barbet C, Mérieau E, et al. CMV infection in the donor and increased kidney graft loss: impact of full HLA-I mismatch and posttransplantation CD8(+) cell reduction. Am J Transplant. 2013;13(8):2119–2129. PMID: 23731368 https://doi.org/10.1111/AJT.12298

73. Razonable R, Rivero A, Rodriguez A, Wilson J, Daniels J, Jenkins G, et al. Allograft rejection predicts the occurrence of late-onset cytomegalovirus (CMV) disease among CMV-mismatched solid organ transplant patients receiving prophylaxis with oral ganciclovir. J Infect Dis. 2001;184(11):1461–1464. PMID: 11709790 https://doi.org/10.1086/324516

74. van Ree RM, de Vries APJ, Zelle DM, de Vries LV, Oterdoom LH, Gans ROB, et al. Latent cytomegalovirus infection is an independent risk factor for late graft failure in renal transplant recipients. Med Sci Monit. 2011;17(11):CR609–617. PMID: 22037739 https://doi.org/10.12659/MSM.882045