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Review

Cytomegalovirus in hematopoietic stem cell transplant recipients - management of infection

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Pages 1093-1105 | Received 15 Jun 2016, Accepted 26 Sep 2016, Published online: 11 Oct 2016

References

  • Staras SA, Dollard SC, Radford KW, et al. Seroprevalence of cytomegalovirus infection in the United States, 1988-1994. Clin Infect Dis. 2006;43(9):1143–1151.
  • Gandhi MK, Khanna R. Human cytomegalovirus: clinical aspects, immune regulation, and emerging treatments. Lancet Infect Dis. 2004;4(12):725–738.
  • Ljungman P, Griffiths P, Paya C. Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis. 2002;34(8):1094–1097.
  • George B, Pati N, Gilroy N, et al. Pre-transplant cytomegalovirus (CMV) serostatus remains the most important determinant of CMV reactivation after allogeneic hematopoietic stem cell transplantation in the era of surveillance and preemptive therapy. Transpl Infect Dis. 2010;12(4):322–329.
  • Rowe RG, Guo D, Lee M, et al. Cytomegalovirus infection in pediatric hematopoietic stem cell transplantation: risk factors for primary infection and cases of recurrent and late infection at a single center. Biol Blood Marrow Transplant. 2016;22(7):1275–1283.
  • Boeckh M, Nichols WG, Papanicolaou G, et al. Cytomegalovirus in hematopoietic stem cell transplant recipients: current status, known challenges, and future strategies. Biol Blood Marrow Transplant. 2003;9(9):543–558.
  • Boeckh M, Gooley TA, Myerson D, et al. 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):4063–4071.
  • Einsele H, Ehninger G, Hebart H, et al. Polymerase chain reaction monitoring reduces the incidence of cytomegalovirus disease and the duration and side effects of antiviral therapy after bone marrow transplantation. Blood. 1995;86(7):2815–2820.
  • Albano MS, Taylor P, Pass RF, et al. Umbilical cord blood transplantation and cytomegalovirus: posttransplantation infection and donor screening. Blood. 2006;108(13):4275–4282.
  • Bregante S, Bertilson S, Tedone E, et al. Foscarnet prophylaxis of cytomegalovirus infections in patients undergoing allogeneic bone marrow transplantation (BMT): a dose-finding study. Bone Marrow Transplant. 2000;26(1):23–29.
  • 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(5067):238–241.
  • Walter EA, Greenberg PD, Gilbert MJ, et al. Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor. N Engl J Med. 1995;333(16):1038–1044.
  • Plotkin S. The history of vaccination against cytomegalovirus. Med Microbiol Immunol. 2015;204(3):247–254.
  • Griffiths P, Plotkin S, Mocarski E, et al. Desirability and feasibility of a vaccine against cytomegalovirus. Vaccine. 2013;31(Suppl 2):B197–203.
  • 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.
  • Mariotti J, Maura F, Spina F, et al. Impact of cytomegalovirus replication and cytomegalovirus serostatus on the outcome of patients with B cell lymphoma after allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2014;20(6):885–890.
  • Srinivasan A, Wang C, Srivastava DK, et al. Timeline, epidemiology, and risk factors for bacterial, fungal, and viral infections in children and adolescents after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2013;19(1):94–101.
  • Kondo K, Xu J, Mocarski ES. Human cytomegalovirus latent gene expression in granulocyte-macrophage progenitors in culture and in seropositive individuals. Proc Natl Acad Sci U S A. 1996;93(20):11137–11142.
  • Taylor-Wiedeman J, Sissons JG, Borysiewicz LK, et al. Monocytes are a major site of persistence of human cytomegalovirus in peripheral blood mononuclear cells. J Gen Virol. 1991;72(Pt 9):2059–2064.
  • Pergam SA, Xie H, Sandhu R, et al. Efficiency and risk factors for CMV transmission in seronegative hematopoietic stem cell recipients. Biol Blood Marrow Transplant. 2012;18(9):1391–1400.
  • Nichols WG, Corey L, Gooley T, et al. High risk of death due to bacterial and fungal infection among cytomegalovirus (CMV)-seronegative recipients of stem cell transplants from seropositive donors: evidence for indirect effects of primary CMV infection. J Infect Dis. 2002;185(3):273–282.
  • Bowden RA, Sayers M, Flournoy N, et al. Cytomegalovirus immune globulin and seronegative blood products to prevent primary cytomegalovirus infection after marrow transplantation. N Engl J Med. 1986;314(16):1006–1010.
  • 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.
  • 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. Prevention of transfusion-transmitted cytomegalovirus infection after allogeneic HCT: the debate continues. Biol Blood Marrow Transplant. 1659-1660;19(12):2013.
  • Boeckh M, Ljungman P. How we treat cytomegalovirus in hematopoietic cell transplant recipients. Blood. 2009;113(23):5711–5719.
  • Bilgin YM, Van De Watering LM, Brand A. Clinical effects of leucoreduction of blood transfusions. Neth J Med. 2011;69(10):441–450.
  • Mainou M, Alahdab F, Tobian AA, et al. Reducing the risk of transfusion-transmitted cytomegalovirus infection: a systematic review and meta-analysis. Transfusion. 2016;56(6 Pt 2):1569–1580.
  • Heddle NM, Boeckh M, Grossman B, et al. AABB Committee Report: reducing transfusion-transmitted cytomegalovirus infections. Transfusion. 2016;56(6 Pt 2):1581–1587.
  • van der Bij W, Torensma R, van Son WJ, et al. Rapid immunodiagnosis of active cytomegalovirus infection by monoclonal antibody staining of blood leucocytes. J Med Virol. 1988;25(2):179–188.
  • Cortez KJ, Fischer SH, Fahle GA, et al. Clinical trial of quantitative real-time polymerase chain reaction for detection of cytomegalovirus in peripheral blood of allogeneic hematopoietic stem-cell transplant recipients. J Infect Dis. 2003;188(7):967–972.
  • Gor D, Sabin C, Prentice HG, et al. Longitudinal fluctuations in cytomegalovirus load in bone marrow transplant patients: relationship between peak virus load, donor/recipient serostatus, acute GVHD and CMV disease. Bone Marrow Transplant. 1998;21(6):597–605.
  • Emery VC, Sabin CA, Cope AV, et al. Application of viral-load kinetics to identify patients who develop cytomegalovirus disease after transplantation. Lancet. 2000;355(9220):2032–2036.
  • Halfon P, Berger P, Khiri H, et al. Algorithm based on CMV kinetics DNA viral load for preemptive therapy initiation after hematopoietic cell transplantation. J Med Virol. 2011;83(3):490–495.
  • Lilleri D, Gerna G, Furione M, et al. Use of a DNAemia cut-off for monitoring human cytomegalovirus infection reduces the number of preemptively treated children and young adults receiving hematopoietic stem-cell transplantation compared with qualitative pp65 antigenemia. Blood. 2007;110(7):2757–2760.
  • Emery VC, Cope AV, Bowen EF, et al. The dynamics of human cytomegalovirus replication in vivo. J Exp Med. 1999;190(2):177–182.
  • Boeckh M, Huang M, Ferrenberg J, et al. Optimization of quantitative detection of cytomegalovirus DNA in plasma by real-time PCR. J Clin Microbiol. 2004;42(3):1142–1148.
  • Lilleri D, Gerna G, Zelini P, et al. Monitoring of human cytomegalovirus and virus-specific T-cell response in young patients receiving allogeneic hematopoietic stem cell transplantation. PLoS One. 2012;7(7):e41648.
  • Lilleri D, Gerna G, Fornara C, et al. Human cytomegalovirus-specific T cell reconstitution in young patients receiving T cell-depleted, allogeneic hematopoietic stem cell transplantation. J Infect Dis. 2009;199(6):829–836.
  • Brooimans RA, Boyce CS, Popma J, et al. Analytical performance of a standardized single-platform MHC tetramer assay for the identification and enumeration of CMV-specific CD8+ T lymphocytes. Cytometry A. 2008;73(11):992–1000.
  • Gratama JW, Boeckh M, Nakamura R, et al. Immune monitoring with iTAg MHC tetramers for prediction of recurrent or persistent cytomegalovirus infection or disease in allogeneic hematopoietic stem cell transplant recipients: a prospective multicenter study. Blood. 2010;116(10):1655–1662.
  • Altman JD, Moss PA, Goulder PJ, et al. Phenotypic analysis of antigen-specific T lymphocytes. Science. 1996;274(5284):94–96.
  • Raeiszadeh M, Pachnio A, Begum J, et al. Characterization of CMV-specific CD4+ T-cell reconstitution following stem cell transplantation through the use of HLA class II-peptide tetramers identifies patients at high risk of recurrent CMV reactivation. Haematologica. 2015;100(8):e318–322.
  • Lilleri D, Gerna G, Fornara C, et al. Prospective simultaneous quantification of human cytomegalovirus-specific CD4+ and CD8+ T-cell reconstitution in young recipients of allogeneic hematopoietic stem cell transplants. Blood. 2006;108(4):1406–1412.
  • Della Chiesa M, Falco M, Bertaina A, et al. Human cytomegalovirus infection promotes rapid maturation of NK cells expressing activating killer Ig-like receptor in patients transplanted with NKG2C-/- umbilical cord blood. J Immunol. 2014;192(4):1471–1479.
  • Della Chiesa M, Falco M, Podesta M, et al. Phenotypic and functional heterogeneity of human NK cells developing after umbilical cord blood transplantation: a role for human cytomegalovirus? Blood. 2012;119(2):399–410.
  • Della Chiesa M, Moretta L, Muccio L, et al. Haploidentical haematopoietic stem cell transplantation: role of NK cells and effect of cytomegalovirus infections. Curr Top Microbiol Immunol. 2016;395:209–224.
  • Vantourout P, Hayday A. Six-of-the-best: unique contributions of gammadelta T cells to immunology. Nat Rev Immunol. 2013;13(2):88–100.
  • Couzi L, Levaillant Y, Jamai A, et al. Cytomegalovirus-induced gammadelta T cells associate with reduced cancer risk after kidney transplantation. J Am Soc Nephrol. 2010;21(1):181–188.
  • Airoldi I, Bertaina A, Prigione I, et al. Gammadelta T-cell reconstitution after HLA-haploidentical hematopoietic transplantation depleted of TCR-alphabeta+/CD19+ lymphocytes. Blood. 2015;125(15):2349–2358.
  • Nguyen VH, Shashidhar S, Chang DS, et al. The impact of regulatory T cells on T-cell immunity following hematopoietic cell transplantation. Blood. 2008;111(2):945–953.
  • Ngoma AM, Ikeda K, Hashimoto Y, et al. Impaired regulatory T cell reconstitution in patients with acute graft-versus-host disease and cytomegalovirus infection after allogeneic bone marrow transplantation. Int J Hematol. 2012;95(1):86–94.
  • Velaga S, Ukena SN, Hopting M, et al. Reconstitution and phenotype of Tregs in CMV reactivating patients following allogeneic hematopoietic stem cell transplantation. Immunol Invest. 2013;42(1):18–35.
  • Boeckh M, Murphy WJ, Peggs KS. Recent advances in cytomegalovirus: an update on pharmacologic and cellular therapies. Biol Blood Marrow Transplant. 2015;21(1):24–29.
  • Emery V, Zuckerman M, Jackson G, et al. Management of cytomegalovirus infection in haemopoietic stem cell transplantation. Br J Haematol. 2013;162(1):25–39.
  • Kim ST, Lee MH, Kim SY, et al. A randomized trial of preemptive therapy for prevention of cytomegalovirus disease after allogeneic hematopoietic stem cell transplantation. Int J Hematol. 2010;91(5):886–891.
  • Park SY, Lee SO, Choi SH, et al. Efficacy and safety of low-dose ganciclovir preemptive therapy in allogeneic haematopoietic stem cell transplant recipients compared with conventional-dose ganciclovir: a prospective observational study. J Antimicrob Chemother. 2012;67(6):1486–1492.
  • Ljungman P, Cordonnier C, Einsele H, et al. Use of intravenous immune globulin in addition to antiviral therapy in the treatment of CMV gastrointestinal disease in allogeneic bone marrow transplant patients: a report from the European Group for Blood and Marrow Transplantation (EBMT). Infectious diseases working party of the EBMT. Bone Marrow Transplant. 1998;21(5):473–476.
  • 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.
  • Chawla JS, Ghobadi A, Mosley J 3rd, et al. Oral valganciclovir versus ganciclovir as delayed pre-emptive therapy for patients after allogeneic hematopoietic stem cell transplant: a pilot trial (04-0274) and review of the literature. Transpl Infect Dis. 2012;14(3):259–267.
  • Asberg A, Humar A, Jardine AG, et al. Long-term outcomes of CMV disease treatment with valganciclovir versus IV ganciclovir in solid organ transplant recipients. Am J Transplant. 2009;9(5):1205–1213.
  • Barkam C, Kamal H, Dammann E, et al. Improving safety of preemptive therapy with oral valganciclovir for cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation. Bone Marrow Res. 2012;2012:874601.
  • Ruiz-Camps I, Len O, de la Camara R, et al. Valganciclovir as pre-emptive therapy for cytomegalovirus infection in allogeneic haematopoietic stem cell transplant recipients. Antivir Ther. 2011;16(7):951–957.
  • Moretti S, Zikos P, Van Lint MT. et al. Forscarnet vs ganciclovir for cytomegalovirus (CMV) antigenemia after allogeneic hemopoietic stem cell transplantation (HSCT): a randomised study. Bone Marrow Transplant. 1998;22(2):175–180.
  • Reusser P, Einsele H, Lee J, et al. Randomized multicenter trial of foscarnet versus ganciclovir for preemptive therapy of cytomegalovirus infection after allogeneic stem cell transplantation. Blood. 2002;99(4):1159–1164.
  • Ishiyama K, Katagiri T, Ohata K, et al. Safety of pre-engraftment prophylactic foscarnet administration after allogeneic stem cell transplantation. Transpl Infect Dis. 2012;14(1):33–39.
  • Bacigalupo A, Boyd A, Slipper J, et al. Foscarnet in the management of cytomegalovirus infections in hematopoietic stem cell transplant patients. Expert Rev Anti Infect Ther. 2012;10(11):1249–1264.
  • Caruso Brown AE, Cohen MN, Tong S, et al. Pharmacokinetics and safety of intravenous cidofovir for life-threatening viral infections in pediatric hematopoietic stem cell transplant recipients. Antimicrob Agents Chemother. 2015;59(7):3718–3725.
  • Chakrabarti S, Collingham KE, Osman H, et al. Cidofovir as primary pre-emptive therapy for post-transplant cytomegalovirus infections. Bone Marrow Transplant. 2001;28(9):879–881.
  • Ljungman P, Deliliers GL, Platzbecker U, et al. Cidofovir for cytomegalovirus infection and disease in allogeneic stem cell transplant recipients. The Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Blood. 2001;97(2):388–392.
  • Gohring K, Wolf D, Bethge W, et al. Dynamics of coexisting HCMV-UL97 and UL54 drug-resistance associated mutations in patients after haematopoietic cell transplantation. J Clin Virol. 2013;57(1):43–49.
  • Van Der Beek MT, Marijt EW, Vossen AC, et al. Failure of pre-emptive treatment of cytomegalovirus infections and antiviral resistance in stem cell transplant recipients. Antivir Ther. 2012;17(1):45–51.
  • Hanson KE, Swaminathan S. Cytomegalovirus antiviral drug resistance: future prospects for prevention, detection and management. Future Microbiol. 2015;10(10):1545–1548.
  • Lischka P, Hewlett G, Wunberg T, et al. In vitro and in vivo activities of the novel anticytomegalovirus compound AIC246. Antimicrob Agents Chemother. 2010;54(3):1290–1297.
  • Snydman DR. Leflunomide: a small step forward in meeting the urgent need for treatment of drug-resistant cytomegalovirus infection. Transplantation. 2010;90(4):362–363.
  • Prichard MN. Function of human cytomegalovirus UL97 kinase in viral infection and its inhibition by maribavir. Rev Med Virol. 2009;19(4):215–229.
  • Chou S, Marousek GI. Maribavir antagonizes the antiviral action of ganciclovir on human cytomegalovirus. Antimicrob Agents Chemother. 2006;50(10):3470–3472.
  • Winston DJ, Young JA, Pullarkat V, et al. Maribavir prophylaxis for prevention of cytomegalovirus infection in allogeneic stem cell transplant recipients: a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study. Blood. 2008;111(11):5403–5410.
  • 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):284–292.
  • Snydman DR. Why did maribavir fail in stem-cell transplants? Lancet Infect Dis. 2011;11(4):255–257.
  • Hostetler KY. Alkoxyalkyl prodrugs of acyclic nucleoside phosphonates enhance oral antiviral activity and reduce toxicity: current state of the art. Antiviral Res. 2009;82(2):A84–98.
  • Painter W, Robertson A, Trost LC, et al. First pharmacokinetic and safety study in humans of the novel lipid antiviral conjugate CMX001, a broad-spectrum oral drug active against double-stranded DNA viruses. Antimicrob Agents Chemother. 2012;56(5):2726–2734.
  • Beadle JR, Hartline C, Aldern KA, et al. Alkoxyalkyl esters of cidofovir and cyclic cidofovir exhibit multiple-log enhancement of antiviral activity against cytomegalovirus and herpesvirus replication in vitro. Antimicrob Agents Chemother. 2002;46(8):2381–2386.
  • Florescu DF, Keck MA. Development of CMX001 (brincidofovir) for the treatment of serious diseases or conditions caused by dsDNA viruses. Expert Rev Anti Infect Ther. 2014;12(10):1171–1178.
  • Marty FM, Winston DJ, Rowley SD, et al. CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. N Engl J Med. 2013;369(13):1227–1236.
  • Marty FM, Winston DJ, Chemaly RF, et al. Brincidofovir for prevention of cytomegalovirus (CMV) after allogeneic hematopoietic cell transplantation (HCT) in CMV-seropositive patients: a randomized, double-blind, placebo-controlled, parallel-group phase 3 trial. Biol. Blood Marrow Transplant. 2016;22(3):S23–S23.
  • Kaul DR, Stoelben S, Cober E, et al. First report of successful treatment of multidrug-resistant cytomegalovirus disease with the novel anti-CMV compound AIC246. Am J Transplant. 2011;11(5):1079–1084.
  • 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.
  • Leen AM, Heslop HE, Brenner MK. Antiviral T-cell therapy. Immunol Rev. 2014;258(1):12–29.
  • Heslop HE, Brenner MK, Rooney CM. Donor T cells to treat EBV-associated lymphoma. N Engl J Med. 1994;331(10):679–680.
  • Bleakley M, Heimfeld S, Loeb KR, et al. Outcomes of acute leukemia patients transplanted with naive T cell-depleted stem cell grafts. J Clin Invest. 2015;125(7):2677–2689.
  • Di Stasi A, Tey SK, Dotti G, et al. Inducible apoptosis as a safety switch for adoptive cell therapy. N Engl J Med. 2011;365(18):1673–1683.
  • Hanley PJ, Cruz CR, Savoldo B, et al. Functionally active virus-specific T cells that target CMV, adenovirus, and EBV can be expanded from naive T-cell populations in cord blood and will target a range of viral epitopes. Blood. 2009;114(9):1958–1967.
  • Hanley PJ, Melenhorst JJ, Nikiforow S, et al. CMV-specific T cells generated from naive T cells recognize atypical epitopes and may be protective in vivo. Sci Transl Med. 2015;7(285):285ra263.
  • Schub A, Schuster IG, Hammerschmidt W, et al. CMV-specific TCR-transgenic T cells for immunotherapy. J Immunol. 2009;183(10):6819–6830.
  • Gerdemann U, Keirnan JM, Katari UL, et al. Rapidly generated multivirus-specific cytotoxic T lymphocytes for the prophylaxis and treatment of viral infections. Mol Ther. 2012;20(8):1622–1632.
  • Heslop HE, Slobod KS, Pule MA, et al. Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients. Blood. 2010;115(5):925–935.
  • Ramirez N, Olavarria E. Viral-specific adoptive immunotherapy after allo-SCT: the role of multimer-based selection strategies. Bone Marrow Transplant. 2013;48(10):1265–1270.
  • Feuchtinger T, Lang P, Hamprecht K, et al. Isolation and expansion of human adenovirus-specific CD4+ and CD8+ T cells according to IFN-gamma secretion for adjuvant immunotherapy. Exp Hematol. 2004;32(3):282–289.
  • Feuchtinger T, Opherk K, Bethge WA, et al. Adoptive transfer of pp65-specific T cells for the treatment of chemorefractory cytomegalovirus disease or reactivation after haploidentical and matched unrelated stem cell transplantation. Blood. 2010;116(20):4360–4367.
  • Icheva V, Kayser S, Wolff D, et al. Adoptive transfer of Epstein-Barr virus (EBV) nuclear antigen 1-specific t cells as treatment for EBV reactivation and lymphoproliferative disorders after allogeneic stem-cell transplantation. J Clin Oncol. 2013;31(1):39–48.
  • Peggs KS, Thomson K, Samuel E, et al. Directly selected cytomegalovirus-reactive donor T cells confer rapid and safe systemic reconstitution of virus-specific immunity following stem cell transplantation. Clin Infect Dis. 2011;52(1):49–57.
  • Leen AM, Bollard CM, Mendizabal AM, et al. Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation. Blood. 2013;121(26):5113–5123.
  • Kapp M, Tan SM, Einsele H, et al. Adoptive immunotherapy of HCMV infection. Cytotherapy. 2007;9(8):699–711.
  • Lucarelli B, Merli P, Bertaina V, et al. Strategies to accelerate immune recovery after allogeneic hematopoietic stem cell transplantation. Expert Rev. Clin. Immunol. 2016;12(3):343–358.
  • Blyth E, Clancy L, Simms R, et al. Donor-derived CMV-specific T cells reduce the requirement for CMV-directed pharmacotherapy after allogeneic stem cell transplantation. Blood. 2013;121(18):3745–3758.
  • 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(11):3916–3922.
  • Peggs KS, Verfuerth S, Pizzey A, et al. Adoptive cellular therapy for early cytomegalovirus infection after allogeneic stem-cell transplantation with virus-specific T-cell lines. Lancet. 2003;362(9393):1375–1377.
  • Moss P, Rickinson A. Cellular immunotherapy for viral infection after HSC transplantation. Nat Rev Immunol. 2005;5(1):9–20.
  • Boeckh M, Gilbert PB. Search continues for a CMV vaccine for transplant recipients. Lancet Haematol. 2016;3(2):e58–59.
  • 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(10):1143–1238.
  • 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.

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