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Cytomegalovirus infection and disease after allogeneic hematopoietic stem cell transplantation: experience in a center with a high seroprevalence of both CMV and hepatitis B virus

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Abstract

Cytomegalovirus (CMV) infection and disease are important concerns after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The similarity of hepatitis B virus (HBV) and CMV with regards to their chronic viral persistence and potential reactivation at the time of impaired cellular immunity has raised clinicians’ interest in the occurrence and association between them among patients receiving allo-HSCT; however, only limited data have been obtained from a high seroprevalence region of both CMV and HBV. We monitored 117 adult allo-HSCT patients with both CMV polymerase chain reaction and pp65 antigenemia assay weekly until day 100. In 91.8% of our cases, donors and recipients were both CMV seropositive, and 13.7% of the patients were positive for HBV surface antigen. The incidences of CMV infection and disease were 45.3% and 6.8%, respectively. Grade II–IV acute graft-versus-host disease and anti-thymocyte globulin-containing conditioning regimen were associated with an increased risk of CMV infection in a multivariate analysis (hazard ratio 3.02, 95% CI 1.68–5.42, p < 0.001 and hazard ratio 5.29, 95% CI 2.57–10.8, p < 0.001). No survival disadvantage was found in patients who developed CMV infection (p = 0.699) and CMV disease (p = 0.093). No clinically significant HBV reactivation was found, and the underlying HBV infection in donors or recipients before allo-HSCT did not increase the risk of CMV infection and CMV disease and did not influence survival after allo-HSCT.

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References

  1. Meyers JD, Flournoy N, Thomas ED (1986) Risk factors for cytomegalovirus infection after human marrow transplantation. J Infect Dis 153:478–488

    Article  PubMed  CAS  Google Scholar 

  2. Boeckh M, Nichols WG, Papanicolaou G, Rubin R, Wingard JR, Zaia J (2003) Cytomegalovirus in hematopoietic stem cell transplant recipients: current status, known challenges, and future strategies. Biol Blood Marrow Transplant 9:543–558

    Article  PubMed  Google Scholar 

  3. Boeckh M, Bowden RA, Gooley T, Myerson D, Corey L (1999) Successful modification of a pp 65 antigenemia-based early treatment strategy for prevention of cytomegalovirus disease in allogeneic marrow transplant recipients. Blood 93:1781–1782

    PubMed  CAS  Google Scholar 

  4. Boeckh M, Gooley TA, Myerson D, Cunningham T, Schoch G, Bowden RA (1996) Cytomegalovirus pp 65 antigenemia-guided early treatment with ganciclovir versus ganciclovir at engraftment after allogeneic marrow transplantation: a randomized double-blind study. Blood 88:4063–4071

    PubMed  CAS  Google Scholar 

  5. Einsele H, Ehninger G, Hebart H, Wittkowski KM, Schuler U, Jahn G et al (1995) Polymerase chain reaction monitoring reduces the incidence of cytomegalovirus disease and the duration and side effects of antiviral therapy after bone marrow transplantation. Blood 86:2815–2820

    PubMed  CAS  Google Scholar 

  6. Reusser P, Einsele H, Lee J, Volin L, Rovira M, Engelhard D et al (2002) 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 99:1159–1164

    Article  PubMed  CAS  Google Scholar 

  7. Ljungman P, Aschan J, Lewensohn-Fuchs I, Carlens S, Larsson K, Lonnqvist B et al (1998) Results of different strategies for reducing cytomegalovirus-associated mortality in allogeneic stem cell transplant recipients. Transplantation 66:1330–1334

    Article  PubMed  CAS  Google Scholar 

  8. Boeckh M, Boivin G (1998) Quantitation of cytomegalovirus: methodologic aspects and clinical applications. Clin Microbiol Rev 11:533–554

    PubMed  CAS  Google Scholar 

  9. Boeckh M, Bowden RA, Goodrich JM, Pettinger M, Meyers JD (1992) Cytomegalovirus antigen detection in peripheral blood leukocytes after allogeneic marrow transplantation. Blood 80:1358–1364

    PubMed  CAS  Google Scholar 

  10. Ljungman P, Lore K, Aschan J, Klaesson S, Lewensohn-Fuchs I, Lonnqvist B et al (1996) Use of a semi-quantitative PCR for cytomegalovirus DNA as a basis for pre-emptive antiviral therapy in allogeneic bone marrow transplant patients. Bone Marrow Transplant 17:583–587

    PubMed  CAS  Google Scholar 

  11. Ljungman P, Reusser P, de la Camara R, Einsele H, Engelhard D, Ribaud P et al (2004) European Group for Blood and Marrow Transplantation. Management of CMV infections: recommendations from the Infectious Diseases Working Party of the EBMT. Bone Marrow Transpl 33:1075–1081

    Article  CAS  Google Scholar 

  12. Nichols WG, Corey L, Gooley T, Davis C, Boeckh M (2002) 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 185:273–282

    Article  PubMed  Google Scholar 

  13. Boeckh M, Nichols WG (2004) The impact of cytomegalovirus serostatus of donor and recipient before hematopoietic stem cell transplantation in the era of antiviral prophylaxis and preemptive therapy. Blood 103:2003–2008

    Article  PubMed  CAS  Google Scholar 

  14. Ljungman P, Brand R, Einsele H, Frassoni F, Niederwieser D, Cordonnier C (2003) Donor CMV serological status and outcome of CMV seropositive recipients after unrelated donor stem cell transplantation: an EBMT megafile analysis. Blood 102:4255–4260

    Article  PubMed  CAS  Google Scholar 

  15. McGlave PB, Shu XO, Wen W, Anasetti C, Nademanee A, Champlin R et al (2000) Unrelated donor marrow transplantation for chronic myelogenous leukemia: 9 years' experience of the national marrow donor program. Blood 95:2219–2225

    PubMed  CAS  Google Scholar 

  16. Kroger N, Zabelina T, Kruger W, Renges H, Stute N, Schrum J et al (2001) Patient cytomegalovirus seropositivity with or without reactivation is the most important prognostic factor for survival and treatment-related mortality in stem cell transplantation from unrelated donors using pretransplant in vivo T-cell depletion with antithymocyte globulin. Br J Haematol 113:1060–1071

    Article  PubMed  CAS  Google Scholar 

  17. Castro-Malaspina H, Harris RE, Gajewski J, Ramsay N, Collins R, Dharan B et al (2002) Unrelated donor marrow transplantation for myelodysplastic syndromes: outcome analysis in 510 transplants facilitated by the National Marrow Donor Program. Blood 99:1943–1951

    Article  PubMed  CAS  Google Scholar 

  18. Craddock C, Szydlo RM, Dazzi F, Olavarria E, Cwynarski K, Yong A et al (2001) Cytomegalovirus seropositivity adversely influences outcome after T-depleted unrelated donor transplant in patients with chronic myeloid leukaemia: the case for tailored graft-versus-host disease prophylaxis. Br J Haematol 112:228–236

    Article  PubMed  CAS  Google Scholar 

  19. Broers AE, van Der Holt R, van Esser JW, Gratama JW, Henzen-Logmans S, Kuenen-Boumeester V et al (2000) 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 95:2240–2245

    PubMed  CAS  Google Scholar 

  20. Meijer E, Dekker AW, Rozenberg-Arska M, Weersink AJ, Verdonck LF (2002) Influence of cytomegalovirus seropositivity on outcome after T cell-depleted bone marrow transplantation: contrasting results between recipients of grafts from related and unrelated donors. Clin Infect Dis 35:703–712

    Article  PubMed  Google Scholar 

  21. Lu SC, Chin LT, Wu FM, Hsieh GJ, Haung SP, Chen JC et al (1999) Seroprevalence of CMV antibodies in a blood donor population and premature neonates in the south-central Taiwan. Kaohsiung J Med Sci 15:603–610

    PubMed  CAS  Google Scholar 

  22. Marshall GS, Stout GG (2005) Cytomegalovirus seroprevalence among women of childbearing age during a 10-year period. Am J Perinatol 22:371–376

    Article  PubMed  Google Scholar 

  23. Mustakangas P, Sarna S, Ammala P, Muttilainen M, Koskela P, Koskiniemi M (2000) Human cytomegalovirus seroprevalence in three socioeconomically different urban areas during the first trimester: a population-based cohort study. Int J Epidemiol 29:587–591

    Article  PubMed  CAS  Google Scholar 

  24. Gratacap-Cavallier B, Bosson JL, Morand P, Dutertre N, Chanzy B, Jouk PS et al (1998) Cytomegalovirus seroprevalence in French pregnant women: parity and place of birth as major predictive factors. Eur J Epidemiol 14:147–152

    Article  PubMed  CAS  Google Scholar 

  25. Natali A, Valcavi P, Medici MC, Dieci E, Montali S, Chezzi C (1997) Cytomegalovirus infection in an Italian population: antibody prevalence, virus excretion and maternal transmission. New Microbiol 20:123–133

    PubMed  CAS  Google Scholar 

  26. Ni YH, Chang MH, Huang LM, Chen HL, Hsu HY, Chiu TY et al (2001) Hepatitis B virus infection in children and adolescents in a hyperendemic area: 15 years after mass hepatitis B vaccination. Ann Intern Med 135:796–800

    PubMed  CAS  Google Scholar 

  27. Chen DS, Kuo GC, Sung JL, Lai MY, Sheu JC, Chen PJ et al (1990) Hepatitis C virus infection in an area hyperendemic for hepatitis B and chronic liver disease: the Taiwan experience. J Infect Dis 162:817–822

    Article  PubMed  CAS  Google Scholar 

  28. Lee SD, Chan CY, Wang YJ, Wu JC, Lai KH, Tsai YT et al (1991) Seroepidemiology of hepatitis C virus infection in Taiwan. Hepatology 13:830–833

    Article  PubMed  CAS  Google Scholar 

  29. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al (1995) 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant 15:825–828

    PubMed  CAS  Google Scholar 

  30. Hebart H, Müller C, Löffler J, Jahn G, Einsele H (1996) Monitoring of CMV infection: a comparison of PCR from whole blood, plasma-PCR, pp 65-antigenemia and virus culture in patients after bone marrow transplantation. Bone Marrow Transplant 17(5):861–868

    PubMed  CAS  Google Scholar 

  31. Ljungman P, Griffiths P, Paya C (2002) Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis 34:1094–1097

    Article  PubMed  Google Scholar 

  32. Kollman C, Howe CW, Anasetti C et al (2001) Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age. Blood 98:2043–2051

    Article  PubMed  CAS  Google Scholar 

  33. Kanda Y, Mineishi S, Saito T, Seo S, Saito A, Suenaga K et al (2001) Pre-emptive therapy against cytomegalovirus (CMV) disease guided by CMV antigenemia assay after allogeneic hematopoietic stem cell transplantation: a single-center experience in Japan. Bone Marrow Transplant 27:437–444

    Article  PubMed  CAS  Google Scholar 

  34. Yanada M, Yamamoto K, Emi N, Naoe T, Suzuki R, Taji H et al (2003) Cytomegalovirus antigenemia and outcome of patients treated with pre-emptive ganciclovir: retrospective analysis of 241 consecutive patients undergoing allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 32:801–807

    Article  PubMed  CAS  Google Scholar 

  35. Choi SM, Lee DG, Choi JH, Yoo JH, Kim YJ, Park SH et al (2005) Risk-adapted preemptive therapy for cytomegalovirus disease after allogeneic stem cell transplantation: a single-center experience in Korea. Int J Hematol 81:69–74

    Article  PubMed  Google Scholar 

  36. Einsele H, Hebart H, Kauffmann-Schneider C, Sinzger C, Jahn G, Bader P et al (2000) Risk factors for treatment failures in patients receiving PCR-based preemptive therapy for CMV infection. Bone Marrow Transplant 25:757–763

    Article  PubMed  CAS  Google Scholar 

  37. Osarogiagbon RU, Defor TE, Weisdorf MA, Erice A, Weisdorf DJ (2000) CMV antigenemia following bone marrow transplantation: risk factors and outcomes. Biol Blood Marrow Transplant 6:280–288

    Article  PubMed  CAS  Google Scholar 

  38. Winston DJ, Ho WG, Bartoni K, Du Mond C, Ebeling DF, Buhles WC et al (1993) Ganciclovir prophylaxis of cytomegalovirus infection and disease in allogeneic bone marrow transplant recipients. Results of a placebo-controlled, double-blind trial. Ann Intern Med 118(3):179–184

    PubMed  CAS  Google Scholar 

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Correspondence to Sheng-Fung Lin.

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Liu, YC., Lu, PL., Hsiao, HH. et al. Cytomegalovirus infection and disease after allogeneic hematopoietic stem cell transplantation: experience in a center with a high seroprevalence of both CMV and hepatitis B virus. Ann Hematol 91, 587–595 (2012). https://doi.org/10.1007/s00277-011-1351-8

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