TRANSPLANTATION| MAY 7, 2020
How I treat CMV reactivation after allogeneic hematopoietic stem cell transplantationHermann Einsele, Per Ljungman, Michael Boeckh
Blood (2020) 135 (19): 1619–1629.
https://doi.org/10.1182/blood.2019000956
AbstractCytomegalovirus (CMV) reactivation remains one of the most common and life-threatening infectious complications following allogeneic hematopoietic stem cell transplantation, despite novel diagnostic technologies, several novel prophylactic agents, and further improvements in preemptive therapy and treatment of established CMV disease. Treatment decisions for CMV reactivation are becoming increasingly difficult and must take into account whether the patient has received antiviral prophylaxis, the patient’s individual risk profile for CMV disease, CMV-specific T-cell reconstitution, CMV viral load, and the potential drug resistance detected at the time of initiation of antiviral therapy. Thus, we increasingly use personalized treatment strategies for the recipient of an allograft with CMV reactivation based on prior use of anti-CMV prophylaxis, viral load, the assessment of CMV-specific T-cell immunity, and the molecular assessment of resistance to antiviral drugs.
Subjects:
Hematopoiesis and Stem Cells, How I Treat, Transplantation
Topics:
allogeneic hematopoietic stem cell transplant, antiviral prophylaxis, cmv reactivation, cytomegalovirus, viral load result, antiviral agents, t-lymphocytes, allografting
REFERENCES1.Zaia JA, Gallez-Hawkins GM, Tegtmeier BR, et al. Late cytomegalovirus disease in marrow transplantation is predicted by virus load in plasma. J Infect Dis. 1997;176(3):782-785.
2.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):2427-2438.
3.Ljungman P, Schmitt M, Marty FM, et al. A mortality analysis of letermovir prophylaxis for cytomegalovirus (CMV) in CMV-seropositive recipients of allogeneic hematopoietic-cell transplantation [published online ahead of print 8 Jun 2019]. Clin Infect Dis. doi:10.1093/cid/ciz490.
4.Fuji S, Einsele H, Kapp M. Cytomegalovirus disease in hematopoietic stem cell transplant patients: current and future therapeutic options. Curr Opin Infect Dis. 2017;30(4):372-376.
5.Chemaly RF, Chou S, Einsele H, et al; Resistant Definitions Working Group of the Cytomegalovirus Drug Development Forum. 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.
6.Zhou W, Longmate J, Lacey SF, et al. Impact of donor CMV status on viral infection and reconstitution of multifunction CMV-specific T cells in CMV-positive transplant recipients. Blood. 2009;113(25):6465-6476.
7.Einsele H, Mielke S, Grigoleit GU. Diagnosis and treatment of cytomegalovirus 2013. Curr Opin Hematol. 2014;21(6):470-475.
8.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.
9.Schmidt-Hieber M, Tridello G, Ljungman P, et al. The prognostic impact of the cytomegalovirus serostatus in patients with chronic hematological malignancies after allogeneic hematopoietic stem cell transplantation: a report from the Infectious Diseases Working Party of EBMT. Ann Hematol. 2019;98(7):1755-1763.
10.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):2003-2008.
11.Ariza-Heredia EJ, Nesher L, Chemaly RF. Cytomegalovirus diseases after hematopoietic stem cell transplantation: a mini-review. Cancer Lett. 2014;342(1):1-8.
12.Green ML, Leisenring W, Xie H, et al. Cytomegalovirus viral load and mortality after haemopoietic stem cell transplantation in the era of pre-emptive therapy: a retrospective cohort study. Lancet Haematol. 2016;3(3):e119-e127.
13.Sester M, Sester U, Gärtner B, et al. Levels of virus-specific CD4 T cells correlate with cytomegalovirus control and predict virus-induced disease after renal transplantation. Transplantation. 2001;71(9):1287-1294.
14.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):4063-4071.
15.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(8):3060-3067.
16.Einsele H, Ehninger G, Steidle M, et al. Polymerase chain reaction to evaluate antiviral therapy for cytomegalovirus disease. Lancet. 1991;338(8776):1170-1172.
17.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.
18.Marty FM, Rubin RH. The prevention of infection post-transplant: the role of prophylaxis, preemptive and empiric therapy. Transpl Int. 2006;19(1):2-11.
19.Boeckh M, Ljungman P. How we treat cytomegalovirus in hematopoietic cell transplant recipients. Blood. 2009;113(23):5711-5719.
20.Marty FM, Boeckh M. Maribavir and human cytomegalovirus-what happened in the clinical trials and why might the drug have failed? Curr Opin Virol. 2011;1(6):555-562.
21.Chemaly RF, Ullmann AJ, Ehninger G. CMV prophylaxis in hematopoietic-cell transplantation. N Engl J Med. 2014;371(6):576-577.
22.Marty FM, Ljungman P, Chemaly RF, et al. Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation. N Engl J Med. 2017;377(25):2433-2444.
23.Camargo JF, Komanduri KV. Emerging concepts in cytomegalovirus infection following hematopoietic stem cell transplantation. Hematol Oncol Stem Cell Ther. 2017;10(4):233-238.
24.Chemaly RF, Hill JA, Voigt S, Peggs KS. In vitro comparison of currently available and investigational antiviral agents against pathogenic human double-stranded DNA viruses: A systematic literature review. Antiviral Res. 2019;163:50-58.
25.Marty FM, Winston DJ, Chemaly RF, et al; SUPPRESS Trial Clinical Study Group. A randomized, double-blind, placebo-controlled phase 3 trial of oral brincidofovir for cytomegalovirus prophylaxis in allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2019;25(2):369-381.
26.Maertens J, Cordonnier C, Jaksch P, et al. Maribavir for preemptive treatment of cytomegalovirus reactivation. N Engl J Med. 2019;381(12):1136-1147.
27.El Chaer F, Shah DP, Chemaly RF. How I treat resistant cytomegalovirus infection in hematopoietic cell transplantation recipients. Blood. 2016;128(23):2624-2636.
28.Griffiths P. New vaccines and antiviral drugs for cytomegalovirus. J Clin Virol. 2019;116:58-61.
29.Chen SJ, Chen YC. Potential application of TALENs against murine cytomegalovirus latent infections. Viruses. 2019;11(5):E414.
30.Rubin RH. Preemptive therapy in immunocompromised hosts. N Engl J Med. 1991;324(15):1057-1059.
31.Hirsch HH, Martino R, Ward KN, Boeckh M, Einsele H, Ljungman P. Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis and treatment of human respiratory syncytial virus, parainfluenza virus, metapneumovirus, rhinovirus, and coronavirus. Clin Infect Dis. 2013;56(2):258-266.
32.Preiksaitis JK, Hayden RT, Tong Y, et al. Are we there yet? Impact of the First International Standard for Cytomegalovirus DNA on the harmonization of results reported on plasma samples. Clin Infect Dis. 2016;63(5):583-589.
33.Marty FM, Ljungman P, Papanicolaou GA, et al; Maribavir 1263-300 Clinical Study Group. 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.
34.Krause H, Hebart H, Jahn G, Müller CA, Einsele H. Screening for CMV-specific T cell proliferation to identify patients at risk of developing late onset CMV disease. Bone Marrow Transplant. 1997;19(11):1111-1116.
35.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):2240-2245.
36.Craddock C, Grigg AP. T-cell depletion does not necessarily compromise donor stem cell engraftment in patients receiving reduced-intensity conditioning regimens. Bone Marrow Transplant. 2003;31(12):1177-author reply 1179.
37.Boeckh M, Leisenring W, Riddell SR, 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.
38.Miller W, Flynn P, McCullough J, et al. Cytomegalovirus infection after bone marrow transplantation: an association with acute graft-v-host disease. Blood. 1986;67(4):1162-1167.
39.Koskinen P, Lemstrøm K, Mattila S, Häyry P, Nieminen MS. Cytomegalovirus infection associated accelerated heart allograft arteriosclerosis may impair the late function of the graft. Clin Transplant. 1996;10(6 Pt 1):487-493.
40.Nichols WG, Corey L, Gooley T, Davis C, Boeckh M. 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.
41.Larsson K, Aschan J, Remberger M, Ringdén O, Winiarski J, Ljungman P. Reduced risk for extensive chronic graft-versus-host disease in patients receiving transplants with human leukocyte antigen-identical sibling donors given polymerase chain reaction-based preemptive therapy against cytomegalovirus. Transplantation. 2004;77(4):526-531.
42.Cantoni N, Hirsch HH, Khanna N, et al. Evidence for a bidirectional relationship between cytomegalovirus replication and acute graft-versus-host disease. Biol Blood Marrow Transplant. 2010;16(9):1309-1314.
43.Chan ST, Logan AC. The clinical impact of cytomegalovirus infection following allogeneic hematopoietic cell transplantation: why the quest for meaningful prophylaxis still matters. Blood Rev. 2017;31(3):173-183.
44.Tomblyn M, Young JA, Haagenson MD, et al; CIBMTR Infection and Immune Reconstitution Working Committee. Decreased infections in recipients of unrelated donor hematopoietic cell transplantation from donors with an activating KIR genotype. Biol Blood Marrow Transplant. 2010;16(8):1155-1161.
45.Prentice HG, Gluckman E, Powles RL, et al; European Acyclovir for CMV Prophylaxis Study Group. Impact of long-term acyclovir on cytomegalovirus infection and survival after allogeneic bone marrow transplantation. Lancet. 1994;343(8900):749-753.
46.Ljungman P, de La Camara R, Milpied N, et al; Valacyclovir International Bone Marrow Transplant Study Group. Randomized study of valacyclovir as prophylaxis against cytomegalovirus reactivation in recipients of allogeneic bone marrow transplants. Blood. 2002;99(8):3050-3056.
47.Ljungman P, de la Camara R, Robin C, et al; 2017 European Conference on Infections in Leukaemia group. 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.
48.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):664-673.
49.Goodrich JM, Mori M, Gleaves CA, et al. Early treatment with ganciclovir to prevent cytomegalovirus disease after allogeneic bone marrow transplantation. N Engl J Med. 1991;325(23):1601-1607.
50.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):179-184.
51.Salzberger B, Bowden RA, Hackman RC, Davis C, Boeckh M. Neutropenia in allogeneic marrow transplant recipients receiving ganciclovir for prevention of cytomegalovirus disease: risk factors and outcome. Blood. 1997;90(6):2502-2508.
52.Einsele H, Hebart H, Kauffmann-Schneider C, et al. Risk factors for treatment failures in patients receiving PCR-based preemptive therapy for CMV infection. Bone Marrow Transplant. 2000;25(7):757-763.
53.Nakamae H, Storer B, Sandmaier BM, et al. Cytopenias after day 28 in allogeneic hematopoietic cell transplantation: impact of recipient/donor factors, transplant conditions and myelotoxic drugs. Haematologica. 2011;96(12):1838-1845.
54.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):473-479.
55.Bacigalupo A, Tedone E, Van Lint MT, et al. CMV prophylaxis with foscarnet in allogeneic bone marrow transplant recipients at high risk of developing CMV infections. Bone Marrow Transplant. 1994;13(6):783-788.
56.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.
57.Reusser P, Einsele H, Lee J, et al; Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Randomized multicenter trial of foscarnet versus ganciclovir for preemptive therapy of cytomegalovirus infection after allogeneic stem cell transplantation. Blood. 2002;99(4):1159-1164.
58.Robin C, Hémery F, Dindorf C, 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(1):747.
59.Yong MK, Ananda-Rajah M, Cameron PU, et al. Cytomegalovirus reactivation is associated with increased risk of late-onset invasive fungal disease after allogeneic hematopoietic stem cell transplantation: a multicenter study in the current era of viral load monitoring. Biol Blood Marrow Transplant. 2017;23(11):1961-1967.
60.Montesinos P, Sanz J, Cantero S, et al. Incidence, risk factors, and outcome of cytomegalovirus infection and disease in patients receiving prophylaxis with oral valganciclovir or intravenous ganciclovir after umbilical cord blood transplantation. Biol Blood Marrow Transplant. 2009;15(6):730-740.
61.Milano F, Pergam SA, Xie H, et al. Intensive strategy to prevent CMV disease in seropositive umbilical cord blood transplant recipients. Blood. 2011;118(20):5689-5696.
62.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.
63.Chen K, Cheng MP, Hammond SP, Einsele H, Marty FM. Antiviral prophylaxis for cytomegalovirus infection in allogeneic hematopoietic cell transplantation. Blood Adv. 2018;2(16):2159-2175.
64.Kropeit D, von Richter O, Stobernack HP, Rübsamen-Schaeff H, Zimmermann H. Pharmacokinetics and safety of letermovir coadministered with cyclosporine a or tacrolimus in healthy subjects. Clin Pharmacol Drug Dev. 2018;7(1):9-21.
65.Maertens J, Bermúdez A, Logan A, et al. A randomised, placebo-controlled phase 3 study to evaluate the efficacy and safety of ASP0113, a first-in-class, DNA-based vaccine in CMV-seropositive allogeneic haematopoietic cell transplant recipients. In: 45th Annual Meeting of the European Society for Blood and Marrow Transplantation, Frankfurt am Main, Germany 24-27 March 2019, abstract OS6.
66.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):290-299.
67.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-e98.
68.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.
69.Marty FM, Winston DJ, Rowley SD, et al; CMX001-201 Clinical Study Group. CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. N Engl J Med. 2013;369(13):1227-1236.
70.Jung S, Michel M, Stamminger T, Michel D. Fast breakthrough of resistant cytomegalovirus during secondary letermovir prophylaxis in a hematopoietic stem cell transplant recipient. BMC Infect Dis. 2019;19(1):388.
71.Goldner T, Hempel C, Ruebsamen-Schaeff H, Zimmermann H, Lischka P. Geno- and phenotypic characterization of human cytomegalovirus mutants selected in vitro after letermovir (AIC246) exposure. Antimicrob Agents Chemother. 2014;58(1):610-613.
72.Boeckh M, Gallez-Hawkins GM, Myerson D, Zaia JA, Bowden RA. Plasma polymerase chain reaction for cytomegalovirus DNA after allogeneic marrow transplantation: comparison with polymerase chain reaction using peripheral blood leukocytes, pp65 antigenemia, and viral culture. Transplantation. 1997;64(1):108-113.
73.Erice A, Chou S, Biron KK, Stanat SC, Balfour HH Jr., Jordan MC. Progressive disease due to ganciclovir-resistant cytomegalovirus in immunocompromised patients. N Engl J Med. 1989;320(5):289-293.
74.Gilbert C, Roy J, Belanger R, et al. Lack of emergence of cytomegalovirus UL97 mutations conferring ganciclovir (GCV) resistance following preemptive GCV therapy in allogeneic stem cell transplant recipients. Antimicrob Agents Chemother. 2001;45(12):3669-3671.
75.Hantz S, Garnier-Geoffroy F, Mazeron MC, et al; French CMV Resistance Survey Study Group. Drug-resistant cytomegalovirus in transplant recipients: a French cohort study. J Antimicrob Chemother. 2010;65(12):2628-2640.
76.Allice T, Busca A, Locatelli F, Falda M, Pittaluga F, Ghisetti V. Valganciclovir as pre-emptive therapy for cytomegalovirus infection post-allogenic stem cell transplantation: implications for the emergence of drug-resistant cytomegalovirus. J Antimicrob Chemother. 2009;63(3):600-608.
77.Shmueli E, Or R, Shapira MY, et al. High rate of cytomegalovirus drug resistance among patients receiving preemptive antiviral treatment after haploidentical stem cell transplantation. J Infect Dis. 2014;209(4):557-561.
78.Tängdén T, Cojutti PG, Roberts JA, Pea F. Valganciclovir pharmacokinetics in patients receiving oral prophylaxis following kidney transplantation and model-based predictions of optimal dosing regimens. Clin Pharmacokinet. 2018;57(11):1399-1405.
79.Åsberg A, Bjerre A, Neely M. New algorithm for valganciclovir dosing in pediatric solid organ transplant recipients. Pediatr Transplant. 2014;18(1):103-111.
80.Kuritzkes DR, Parenti D, Ward DJ, et al. Filgrastim prevents severe neutropenia and reduces infective morbidity in patients with advanced HIV infection: results of a randomized, multicenter, controlled trial. G-CSF 930101 Study Group. AIDS. 1998;12(1):65-74.
81.Dubreuil-Lemaire ML, Gori A, Vittecoq D, et al; GCS 309 European Study Group. Lenograstim for the treatment of neutropenia in patients receiving ganciclovir for cytomegalovirus infection: a randomised, placebo-controlled trial in AIDS patients. Eur J Haematol. 2000;65(5):337-343.
82.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.
83.Tzannou I, Papadopoulou A, Naik S, et al. Off-the-shelf virus-specific T cells to treat BK virus, human herpesvirus 6, cytomegalovirus, Epstein-Barr virus, and adenovirus infections after allogeneic hematopoietic stem-cell transplantation. J Clin Oncol. 2017;35(31):3547-3557.
84.Tzannou I, Leen AM. Preventing stem cell transplantation-associated viral infections using T-cell therapy. Immunotherapy. 2015;7(7):793-810.
85.Papadopoulou A, Gerdemann U, Katari UL, et al. Activity of broad-spectrum T cells as treatment for AdV, EBV, CMV, BKV, and HHV6 infections after HSCT. Sci Transl Med. 2014;6(242):242ra83.
86.Rooney CM, Leen AM, Vera JF, Heslop HE. T lymphocytes targeting native receptors. Immunol Rev. 2014;257(1):39-55.
87.Neuenhahn M, Albrecht J, Odendahl M, et al. Transfer of minimally manipulated CMV-specific T cells from stem cell or third-party donors to treat CMV infection after allo-HSCT. Leukemia. 2017;31(10):2161-2171.
88.Wolf DG, Shimoni A, Resnick IB, et al. Human cytomegalovirus kinetics following institution of artesunate after hematopoietic stem cell transplantation. Antiviral Res. 2011;90(3):183-186.
89.Stuehler C, Stüssi G, Halter J, et al. Combination therapy for multidrug-resistant cytomegalovirus disease. Transpl Infect Dis. 2015;17(5):751-755.
90.Gokarn A, Toshniwal A, Pathak A, et al. Use of leflunomide for treatment of cytomegalovirus infection in recipients of allogeneic stem cell transplant. Biol Blood Marrow Transplant. 2019;25(9):1832-1836.
91.El Chaer F, Mori N, Shah D, et al. Adjuvant and salvage therapy with leflunomide for recalcitrant cytomegalovirus infections in hematopoietic cell transplantation recipients: a case series. Antiviral Res. 2016;135:91-96.
92.Avery RK, Bolwell BJ, Yen-Lieberman B, et al. Use of leflunomide in an allogeneic bone marrow transplant recipient with refractory cytomegalovirus infection. Bone Marrow Transplant. 2004;34(12):1071-1075.
93.Papanicolaou GA, Silveira FP, Langston AA, 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.
94.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(5):1373-1380.
95.Hebart H, Brugger W, Grigoleit U, et al. Risk for cytomegalovirus disease in patients receiving polymerase chain reaction-based preemptive antiviral therapy after allogeneic stem cell transplantation depends on transplantation modality. Blood. 2001;97(7):2183-2185.
96.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.
97.Lee SM, Kim YJ, Yoo KH, Sung KW, Koo HH, Kang ES. Clinical usefulness of monitoring cytomegalovirus-specific immunity by QuantiFERON-CMV in pediatric allogeneic hematopoietic stem cell transplantation recipients. Ann Lab Med. 2017;37(3):277-281.
98.Krawczyk A, Ackermann J, Goitowski B, et al. Assessing the risk of CMV reactivation and reconstitution of antiviral immune response post bone marrow transplantation by the QuantiFERON-CMV-assay and real time PCR. J Clin Virol. 2018;99-100:61-66.
99.Paouri B, Soldatou A, Petrakou E, et al. QuantiFERON-Cytomegalovirus assay: a potentially useful tool in the evaluation of CMV-specific CD8+ T-cell reconstitution in pediatric hematopoietic stem cell transplant patients. Pediatr Transplant. 2018;22(5):e13220.
100.Gliga S, Korth J, Krawczyk A, et al. T-Track-CMV and QuantiFERON-CMV assays for prediction of protection from CMV reactivation in kidney transplant recipients. J Clin Virol. 2018;105:91-96.
101.Bono P, Orlandi A, Zoccoli A, et al. QuantiFERON CMV assay in allogenic stem cell transplant patients. J Clin Virol. 2016;79:10-11.
102.Tey SK, Kennedy GA, Cromer D, et al. Clinical assessment of anti-viral CD8+ T cell immune monitoring using QuantiFERON-CMV assay to identify high risk allogeneic hematopoietic stem cell transplant patients with CMV infection complications. PLoS One. 2013;8(10):e74744.
103.Chanouzas D, Small A, Borrows R, Ball S. Assessment of the T-SPOT.CMV interferon-γ release assay in renal transplant recipients: a single center cohort study. PLoS One. 2018;13(3):e0193968.
104.Banas B, Steubl D, Renders L, et al. Clinical validation of a novel enzyme-linked immunosorbent spot assay-based in vitro diagnostic assay to monitor cytomegalovirus-specific cell-mediated immunity in kidney transplant recipients: a multicenter, longitudinal, prospective, observational study. Transpl Int. 2018;31(4):436-450.
105.El Haddad L, Ariza-Heredia E, Shah DP, et al. The ability of a cytomegalovirus ELISPOT assay to predict outcome of low-level CMV reactivation in hematopoietic cell transplant recipients. J Infect Dis. 2019;219(6):898-907.
106.Kumar D, Mian M, Singer L, Humar A. An interventional study using cell-mediated immunity to personalize therapy for cytomegalovirus infection after transplantation. Am J Transplant. 2017;17(9):2468-2473.
107.Green ML, Leisenring W, Stachel D, et al. Efficacy of a viral load-based, risk-adapted, preemptive treatment strategy for prevention of cytomegalovirus disease after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2012;18(11):1687-1699.
108.Avetisyan G, Aschan J, Hägglund H, Ringdén O, Ljungman P. Evaluation of intervention strategy based on CMV-specific immune responses after allogeneic SCT. Bone Marrow Transplant. 2007;40(9):865-869.
109.Navarro D, Amat P, de la Cámara R, et al. 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 Infect Dis. 2016;3(2):ofw107.
110.Einsele H, Reusser P, Bornhäuser M, et al. Oral valganciclovir leads to higher exposure to ganciclovir than intravenous ganciclovir in patients following allogeneic stem cell transplantation. Blood. 2006;107(7):3002-3008.
111.Flowers MED, McDonald G, Carpenter P, et al. Long-term follow-up after hematopoietic stem cell transplant. General guidelines for referring physicians. Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, version 29 July 2019.
© 2020 by The American Society of Hematology
This program is developed by Focus Insight with the permission of American Society of Hematology, Inc. The content are excerpted from the journal Blood. Copyright © 2019 The American Society of Hematology. All rights reserved. 「American Society of Hematology」, 「ASH」 and the ASH Logo are registered trademarks of the American Society of Hematology.