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Graft-Versus-Host Disease

Blood stream infection (BSI) and acute GVHD after hematopoietic SCT (HSCT) are associated

Bone Marrow Transplantation volume 46, pages 300–307 (2011)Cite this article

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Abstract

Blood stream infection (BSI) and acute GVHD (aGVHD) are serious complications of hematopoietic SCT (HSCT). We hypothesized that the two events were not independent of one another. We studied (1) associations between BSI and aGVHD; and (2) the impact of BSI and/or aGVHD on death within 100 days after HSCT, using a retrospective cohort analysis. Risk factor analysis was carried out using multivariable Cox proportional hazards analyses. Of 211 patients who underwent allogeneic HSCT from January 2000 to December 2005 (58% of whom underwent reduced intensity transplantation), 82 (39%) developed BSI. In 49 patients (23%), grade (gr) 2–4 aGVHD occurred. Early BSI was independently associated with an increased occurrence of subsequent aGVHD gr 2–4. CMV seropositivity was independently associated with decreased occurrence of aGVHD. aGVHD gr 2–4 independently predicted subsequent first BSI. Both BSI and aGVHD gr 2–4 were significant independent predictors of death within 100 days after HSCT. There is a strong, independent association between BSI and aGVHD. Potential explanations include the elaboration of cytokines during BSI favoring the development of aGVHD and/or the immunosuppressive treatment of aGVHD favoring the development of BSI. Future studies should be directed at the mechanistic investigations of this association.

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References

  1. Poutsiaka DD, Price LL, Ucuzian A, Chan GW, Miller KB, Snydman DR . Blood stream infection after hematopoietic stem cell transplantation is associated with increased mortality. Bone Marrow Transplant 2007; 40: 63–70.

    Article  CAS  PubMed  Google Scholar 

  2. Copelan EA . Hematopoietic stem-cell transplantation. [see comment]. New Engl J Med 2006; 354: 1813–1826.

    Article  CAS  PubMed  Google Scholar 

  3. Duran-Struuck R, Reddy P . Biological advances in acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. Transplantation 2008; 85: 303–308.

    Article  PubMed  Google Scholar 

  4. Ferrara JL, Levine JE, Reddy P, Holler E . Graft-versus-host disease. Lancet 2009; 373: 1550–1561.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Miller KB, Roberts TF, Chan G, Schenkein DP, Lawrence D, Sprague K et al. A novel reduced intensity regimen for allogeneic hematopoietic stem cell transplantation associated with a reduced incidence of graft-versus-host disease. Bone Marrow Transplant 2004; 33: 881–889.

    Article  CAS  PubMed  Google Scholar 

  6. Horan T, Gaynes R . Surveillance of nosocomial infections. In: Hospital Epidemiology and Infection Control, 3rd edn. Lippincott, Williams & Wilkeins: Philadelphia, 2004, pp 1659–1702.

  7. DesJardin JA, Falagas ME, Ruthazer R, Griffith J, Wawrose D, Schenkein D et al. Clinical utility of blood cultures drawn from indwelling central venous catheters in hospitalized patients with cancer. Ann Intern Med 1999; 131: 641–647.

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  9. National Cancer Institute. Common Terminology Criteria for Adverse Events. National Cancer Institute: Bethesda, MD, USA, 2006, http://ctep.cancer.gov.

  10. Flowers ME, Traina F, Storer B, Maris M, Bethge WA, Carpenter P et al. Serious graft-versus-host disease after hematopoietic cell transplantation following nonmyeloablative conditioning. Bone Marrow Transplant 2005; 35: 277–282.

    Article  CAS  PubMed  Google Scholar 

  11. Leisenring WM, Martin PJ, Petersdorf EW, Regan AE, Aboulhosn N, Stern JM et al. An acute graft-versus-host disease activity index to predict survival after hematopoietic cell transplantation with myeloablative conditioning regimens. Blood 2006; 108: 749–755.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Bergstralh E, Therneau T . %Schoen.sas. Mayo Foundations for Medical Education and Research: Rochester, MN, USA, 2002, Copyright 2006.

    Google Scholar 

  13. Harrell JFE . %daspline.sas. Mayo Foundations for Medical Education and Research: Rochester, MN, USA, 1991, Copyright 2006.

    Google Scholar 

  14. Allison PD . Survival Analysis Using SAS(TM): A Practical GuideEstimating Cox regression models with PROC PHREG. SAS Institute, Inc.: Cary, NC, 1995.

    Google Scholar 

  15. Wolkewitz M, Vonberg RP, Grundmann H, Beyersmann J, Gastmeier P, Barwolff S et al. Risk factors for the development of nosocomial pneumonia and mortality on intensive care units: application of competing risks models. [see comment]. Critical Care (London, England) 2008; 12: R44.

    Article  Google Scholar 

  16. Neher A, Arnitz R, Gstottner M, Schafer D, Kross EM, Nagl M et al. Antimicrobial activity of dexamethasone and its combination with N-chlorotaurine. Arch Otolaryngol Head Neck Surg 2008; 134: 615–620.

    Article  PubMed  Google Scholar 

  17. Unsal H, Balkaya M, Unsal C, Biyik H, Basbulbul G, Poyrazoglu E et al. The short-term effects of different doses of dexamethasone on the numbers of some bacteria in the ileum. Dig DisSc 2008; 53: 1842–1845.

    Google Scholar 

  18. van Vliet MJ, Tissing WJ, Dun CA, Meessen NE, Kamps WA, de Bont ES et al. Chemotherapy treatment in pediatric patients with acute myeloid leukemia receiving antimicrobial prophylaxis leads to a relative increase of colonization with potentially pathogenic bacteria in the gut. Clin Infect Dis 2009; 49: 262–270.

    Article  CAS  PubMed  Google Scholar 

  19. Johansson JE, Ekman T, Johansson J-E, Ekman T . Gut toxicity during hemopoietic stem cell transplantation may predict acute graft-versus-host disease severity in patients. Dig Dis Sci 2007; 52: 2340–2345.

    Article  PubMed  Google Scholar 

  20. Bostrom L, Ringden O, Sundberg B, Linde A, Tollemar J, Nilsson B . Pretransplant herpesvirus serology and acute graft-versus-host disease. Transplantation 1988; 46: 548–552.

    Article  CAS  PubMed  Google Scholar 

  21. Broers AE, van Der Holt R, van Esser JW, Gratama JW, Henzen-Logmans S, Kuenen-Boumeester V 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: 2240–2245.

    CAS  PubMed  Google Scholar 

  22. Meijer E, Dekker AW, Rozenberg-Arska M, Weersink AJ, Verdonck LF . 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 2002; 35: 703–712.

    Article  PubMed  Google Scholar 

  23. Remberger M, Aschan J, Lonnqvist B, Carlens S, Gustafsson B, Hentschke P et al. An ethnic role for chronic, but not acute, graft-versus-host disease after HLA-identical sibling stem cell transplantation. Eur J Haematol 2001; 66: 50–56.

    Article  CAS  PubMed  Google Scholar 

  24. Gratama JW, Zwaan FE, Stijnen T, Weijers TF, Weiland HT, D’Amaro J et al. Herpes-virus immunity and acute graft-versus-host disease. Lancet 1987; 1: 471–474.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  26. Appleton AL, Sviland L, Peiris JS, Taylor CE, Wilkes J, Green MA et al. Role of target organ infection with cytomegalovirus in the pathogenesis of graft-versus-host disease. Bone Marrow Transplant 1995; 15: 557–561.

    CAS  PubMed  Google Scholar 

  27. Meyers JD, Ljungman P, Fisher LD . Cytomegalovirus excretion as a predictor of cytomegalovirus disease after marrow transplantation: importance of cytomegalovirus viremia. J Infect Dis 1990; 162: 373–380.

    Article  CAS  PubMed  Google Scholar 

  28. Miller W, Flynn P, McCullough J, Balfour Jr HH, Goldman A, Haake R et a.l Cytomegalovirus infection after bone marrow transplantation: an association with acute graft-v-host disease. Blood 1986; 67: 1162–1167.

    CAS  PubMed  Google Scholar 

  29. Asano-Mori Y, Oshima K, Sakata-Yanagimoto M, Nakagawa M, Kandabashi K, Izutsu K et al. High-grade cytomegalovirus antigenemia after hematopoietic stem cell transplantation. Bone Marrow Transplant 2005; 36: 813–819.

    Article  CAS  PubMed  Google Scholar 

  30. Daly A, McAfee S, Dey B, Colby C, Schulte L, Yeap B et al. Nonmyeloablative bone marrow transplantation: Infectious complications in 65 recipients of HLA-identical and mismatched transplants. Biol Blood Marrow Transplant 2003; 9: 373–382.

    Article  PubMed  Google Scholar 

  31. Frere P, Baron F, Bonnet C, Hafraoui K, Pereira M, Willems E et al. Infections after allogeneic hematopoietic stem cell transplantation with a nonmyeloablative conditioning regimen. Bone Marrow Transplant 2006; 37: 411–418.

    Article  CAS  PubMed  Google Scholar 

  32. Lin TS, Zahrieh D, Weller E, Alyea EP, Antin JH, Soiffer RJ . Risk factors for cytomegalovirus reactivation after CD6+ T-cell-depleted allogeneic bone marrow transplantation. Transplantation 2002; 74: 49–54.

    Article  PubMed  Google Scholar 

  33. Matsumura T, Narimatsu H, Kami M, Yuji K, Kusumi E, Hori A et al. Cytomegalovirus infections following umbilical cord blood transplantation using reduced intensity conditioning regimens for adult patients. Biol Blood Marrow Transplant 2007; 13: 577–583.

    Article  PubMed  Google Scholar 

  34. Meyers J, Flournoy N, Thomas E . Risk factors for cytomegalovirus infection after human marrow transplantation. J Infect Dis 1986; 153: 478–488.

    Article  CAS  PubMed  Google Scholar 

  35. Mohty M, Jacot W, Faucher C, Bay JO, Zandotti C, Collet L et al. Infectious complications following allogeneic HLA-identical sibling transplantation with antithymocyte globulin-based reduced intensity preparative regimen. Leukemia 2003; 17: 2168–2177.

    Article  CAS  PubMed  Google Scholar 

  36. Reddy V, Meier-Kriesche HU, Greene S, Schold JD, Wingard JR . Increased levels of tumor necrosis factor alpha are associated with an increased risk of cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2005; 11: 698–705.

    Article  CAS  PubMed  Google Scholar 

  37. van Burik JA, Carter SL, Freifeld AG, High KP, Godder KT, Papanicolaou GA et al. Higher risk of cytomegalovirus and aspergillus infections in recipients of T cell-depleted unrelated bone marrow: analysis of infectious complications in patients treated with T cell depletion versus immunosuppressive therapy to prevent graft-versus-host disease. Biol Blood Marrow Transplant 2007; 13: 1487–1498.

    Article  PubMed  Google Scholar 

  38. Mocarski Jr ES . Immunomodulation by cytomegaloviruses: manipulative strategies beyond evasion. Trends Microbiol 2002; 10: 332–339.

    Article  CAS  PubMed  Google Scholar 

  39. Mocarski Jr ES . Immune escape and exploitation strategies of cytomegaloviruses: impact on and imitation of the major histocompatibility system. Cell Microbiol 2004; 6: 707–717.

    Article  CAS  PubMed  Google Scholar 

  40. Peggs KS, Mackinnon S . Cytomegalovirus: the role of CMV post-haematopoietic stem cell transplantation. Int J Biochem Cell Biol 2004; 36: 695–701.

    Article  CAS  PubMed  Google Scholar 

  41. Sayer HG, Longton G, Bowden R, Pepe M, Storb R . Increased risk of infection in marrow transplant patients receiving methylprednisolone for graft-versus-host disease prevention. Blood 1994; 84: 1328–1332.

    CAS  PubMed  Google Scholar 

  42. Almyroudis NG, Fuller A, Jakubowski A, Sepkowitz K, Jaffe D, Small TN et al. Pre- and post-engraftment bloodstream infection rates and associated mortality in allogeneic hematopoietic stem cell transplant recipients. Transpl Infect Dis 2005; 7: 11–17.

    Article  CAS  PubMed  Google Scholar 

  43. Cappellano P, Viscoli C, Bruzzi P, Van Lint MT, Pereira CA, Bacigalupo A . Epidemiology and risk factors for bloodstream infections after allogeneic hematopoietic stem cell transplantion. New Microbiologica 2007; 30: 89–99.

    PubMed  Google Scholar 

  44. Ninin E, Milpied N, Moreau P, Andre-Richet B, Morineau N, Mahe B et al. Longitudinal study of bacterial, viral, and fungal infections in adult recipients of bone marrow transplants. Clin Infect Dis 2001; 33: 41–47.

    Article  CAS  PubMed  Google Scholar 

  45. Kruger W, Russmann B, Kroger N, Salomon C, Ekopf N, Elsner HA et al. Early infections in patients undergoing bone marrow or blood stem cell transplantation—a 7 year single centre investigation of 409 cases. Bone Marrow Transplant 1999; 23: 589–597.

    Article  CAS  PubMed  Google Scholar 

  46. MacMillan ML, Weisdorf DJ, Wagner JE, DeFor TE, Burns LJ, Ramsay NK et al. Response of 443 patients to steroids as primary therapy for acute graft-versus-host disease: comparison of grading systems. Biol Blood Marrow Transplant 2002; 8: 387–394.

    Article  CAS  PubMed  Google Scholar 

  47. Sparrelid E, Hagglund H, Remberger M, Ringden O, Lonnqvist B, Ljungman P et al. Bacteraemia during the aplastic phase after allogeneic bone marrow transplantation is associated with early death from invasive fungal infection. Bone Marrow Transplant 1998; 22: 795–800.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. de Lissovoy G, Hurd D, Carter S, Beatty P, Ewell M, Henslee-Downey J et al. Economic analysis of unrelated allogeneic bone marrow transplantation: results from the randomized clinical trial of T-cell depletion vs unmanipulated grafts for the prevention of graft-versus-host disease. Bone Marrow Transplant 2005; 36: 539–546.

    Article  CAS  PubMed  Google Scholar 

  49. Esperou H, Brunot A, Roudot-Thoraval F, Buzyn A, Dhedin N, Rio B et al. Predicting the costs of allogeneic sibling stem-cell transplantation: results from a prospective, multicenter, French study. Transplantation 2004; 77: 1854–1858.

    Article  PubMed  Google Scholar 

  50. Moya R, Espigado I, Parody R, Carmona M, Marquez F, De Blas JM . Evaluation of readmissions in hematopoietic stem cell transplant recipients. Transplant Proceedings 2006; 38: 2591–2592.

    Article  CAS  Google Scholar 

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Acknowledgements

This study was supported in part by the National Institutes of Health/National Center for Research Resources (grant 5K23 RR020042-04 to DDP), Tufts Clinical and Translational Science Institute (grants 1UL1RR025752/1KL2RR025751 to DDP), and the Harold William MD Medical Student Research Fellowship, Tufts University School of Medicine (DM).

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Authors and Affiliations

  1. Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA, USA

    D D Poutsiaka, L L Price, G W Chan & D R Snydman

  2. Tufts University School of Medicine, Boston, MA, USA

    D Munson

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Correspondence to D D Poutsiaka.

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Poutsiaka, D., Munson, D., Price, L. et al. Blood stream infection (BSI) and acute GVHD after hematopoietic SCT (HSCT) are associated. Bone Marrow Transplant 46, 300–307 (2011). https://doi.org/10.1038/bmt.2010.112

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