Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Infections

The association between donor and recipient statin use and infections after allogeneic hematopoietic cell transplantation

Abstract

Recent studies have reported that statin use may be associated with improved outcomes in patients with sepsis or respiratory viral infections. In the setting of allogeneic hematopoietic cell transplantation (HCT), it has been shown that donor and recipient statin use is associated with reduced risks of GVHD. We assessed in retrospective analysis whether donor or recipient statin use impacts infection risk after allogeneic HCT (n=1191). Although recipient statin use was associated with the increased incidence of Gram-negative bacteremia (adjusted hazard ratio (aHR) 2.22, (95% confidence interval (CI) 1.2–4.2), P=0.01) without affecting mortality, donor statin use was associated with an increased incidence of respiratory viral infections in recipients (aHR 2.84 (95% CI 1.3–6.0), P=0.007). The overall incidence of invasive fungal infections and CMV reactivation and CMV disease were not impacted by recipient or donor statin use. In conclusion, this study suggests that recipient or donor statin use may be associated with an increased incidence of some infections without adversely affecting mortality.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Terblanche M, Almog Y, Rosenson RS, Smith TS, Hackam DG . Statins and sepsis: multiple modifications at multiple levels. Lancet Infect Dis 2007; 7: 358–368.

    Article  CAS  Google Scholar 

  2. Chalmers JD, Short PM, Mandal P, Akram AR, Hill AT . Statins in community acquired pneumonia: evidence from experimental and clinical studies. Respir Med 2010; 104: 1081–1091.

    Article  Google Scholar 

  3. Bu DX, Griffin G, Lichtman AH . Mechanisms for the anti-inflammatory effects of statins. Curr Opin Lipidol 2011; 22: 165–170.

    Article  CAS  Google Scholar 

  4. Greenwood J, Steinman L, Zamvil SS . Statin therapy and autoimmune disease: from protein prenylation to immunomodulation. Nature Rev Immunol 2006; 6: 358–370.

    Article  CAS  Google Scholar 

  5. van den Hoek HL, Bos WJ, de Boer A, van de Garde EM . Statins and prevention of infections: systematic review and meta-analysis of data from large randomised placebo controlled trials. BMJ 2011; 343: d7281.

    Article  Google Scholar 

  6. Tleyjeh IM, Kashour T, Hakim FA, Zimmerman VA, Erwin PJ, Sutton AJ et al. Statins for the prevention and treatment of infections: a systematic review and meta-analysis. Arch Intern Med 2009; 169: 1658–1667.

    Article  Google Scholar 

  7. Ma Y, Wen X, Peng J, Lu Y, Guo Z, Lu J . Systematic review and meta-analysis on the association between outpatient statins use and infectious disease-related mortality. PLoS ONE 2012; 7: e51548.

    Article  CAS  Google Scholar 

  8. Tleyjeh IM, Alasmari FA, Bin Abdulhak AA, Riaz M, Garbati MA, Erwin PJ et al. Association between preoperative statin therapy and postoperative infectious complications in patients undergoing cardiac surgery: a systematic review and meta-analysis. Infect Control Hosp Epidemiol 2012; 33: 1143–1151.

    Article  Google Scholar 

  9. National Heart Lung, Blood Institute ARDS Clinical Trials Network, Truwit JD, Bernard GR, Steingrub J, Matthay MA, Liu KD, Albertson TE et al. Rosuvastatin for sepsis-associated acute respiratory distress syndrome. N Engl J Med 2014; 370: 2191–2200.

    Article  Google Scholar 

  10. Liappis AP, Kan VL, Rochester CG, Simon GL . The effect of statins on mortality in patients with bacteremia. Clin Infect Dis 2001; 33: 1352–1357.

    Article  CAS  Google Scholar 

  11. Vandermeer ML, Thomas AR, Kamimoto L, Reingold A, Gershman K, Meek J et al. Association between use of statins and mortality among patients hospitalized with laboratory-confirmed influenza virus infections: a multistate study. J Infect Dis 2012; 205: 13–19.

    Article  CAS  Google Scholar 

  12. Hackam DG, Mamdani M, Li P, Redelmeier DA . Statins and sepsis in patients with cardiovascular disease: a population-based cohort analysis. Lancet 2006; 367: 413–418.

    Article  CAS  Google Scholar 

  13. Wan YD, Sun TW, Kan QC, Guan FX, Zhang SG . Effect of statin therapy on mortality from infection and sepsis: a meta-analysis of randomized and observational studies. Crit Care 2014; 18: R71.

    Article  Google Scholar 

  14. Rotta M, Storer BE, Storb R, Martin PJ, Flowers ME, Vernon MS et al. Impact of recipient statin treatment on graft-versus-host disease after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2010; 16: 1463–1466.

    Article  Google Scholar 

  15. Rotta M, Storer BE, Storb RF, Martin PJ, Heimfeld S, Peffer A et al. Donor statin treatment protects against severe acute graft-versus-host disease after related allogeneic hematopoietic cell transplantation. Blood 2010; 115: 1288–1295.

    Article  CAS  Google Scholar 

  16. Hamadani M, Gibson LF, Remick SC, Wen S, Petros W, Tse W et al. Sibling donor and recipient immune modulation with atorvastatin for the prophylaxis of acute graft-versus-host disease. J Clin Oncol 2013; 31: 4416–4423.

    Article  CAS  Google Scholar 

  17. Bock AM, Cao Q, Ferrieri P, Young JA, Weisdorf DJ . Bacteremia in blood or marrow transplantation patients: clinical risk factors for infection and emerging antibiotic resistance. Biol Blood Marrow Transplant 2013; 19: 102–108.

    Article  Google Scholar 

  18. Junghanss C, Marr KA, Carter RA, Sandmaier BM, Maris MB, Maloney DG et al. Incidence and outcome of bacterial and fungal infections following nonmyeloablative compared with myeloablative allogeneic hematopoietic stem cell transplantation: a matched control study. Biol Blood Marrow Transplant 2002; 8: 512–520.

    Article  Google Scholar 

  19. 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  Google Scholar 

  20. Martino R, Kerguelen A, Valcarcel D, Sureda A, Fachini L, Pinana JL et al. Reduction of infection-related mortality after allogeneic PBSCT from HLA-identical siblings: longitudinal analysis from 1994 to 2008 at a single institution. Bone Marrow Transplant 2011; 46: 690–701.

    Article  CAS  Google Scholar 

  21. Viasus D, Gudiol C, Fernandez-Sabe N, Cabello I, Garcia-Vidal C, Cisnal M et al. Effect of statins on outcomes in immunosuppressed patients with bloodstream infection. Eur J Clin Microbiol Infect Dis 2011; 30: 77–82.

    Article  CAS  Google Scholar 

  22. Schubert MM, Williams BE, Lloid ME, Donaldson G, Chapko MK . Clinical assessment scale for the rating of oral mucosal changes associated with bone marrow transplantation. Development of an oral mucositis index. Cancer 1992; 69: 2469–2477.

    Article  CAS  Google Scholar 

  23. De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis 2008; 46: 1813–1821.

    Article  Google Scholar 

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

    Article  Google Scholar 

  25. Seo S, Campbell AP, Xie H, Chien JW, Leisenring WM, Englund JA et al. Outcome of respiratory syncytial virus lower respiratory tract disease in hematopoietic cell transplant recipients receiving aerosolized ribavirin: significance of stem cell source and oxygen requirement. Biol Blood Marrow Transplant 2013; 19: 589–596.

    Article  CAS  Google Scholar 

  26. Antoniou T, Zheng H, Singh S, Juurlink DN, Mamdani MM, Gomes T . Statins and the risk of herpes zoster: a population-based cohort study. Clin Infect Dis 2014; 58: 350–356.

    Article  CAS  Google Scholar 

  27. Zeiser R, Youssef S, Baker J, Kambham N, Steinman L, Negrin RS . Preemptive HMG-CoA reductase inhibition provides graft-versus-host disease protection by Th-2 polarization while sparing graft-versus-leukemia activity. Blood 2007; 110: 4588–4598.

    Article  CAS  Google Scholar 

  28. Weitz-Schmidt G, Welzenbach K, Brinkmann V, Kamata T, Kallen J, Bruns C et al. Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat Med 2001; 7: 687–692.

    Article  CAS  Google Scholar 

  29. Broady R, Levings MK . Graft-versus-host disease: suppression by statins. Nat Med 2008; 14: 1155–1156.

    Article  CAS  Google Scholar 

  30. Kellick KA, Bottorff M, Toth PP . A clinician's guide to statin drug-drug interactions. J Clin lipidol 2014; 8: S30–S46.

    Article  Google Scholar 

  31. Causevic-Ramosevac A, Semiz S . Drug interactions with statins. Acta Pharm 2013; 63: 277–293.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Zachary Stednick for the data retrieval. This work was partially supported by NIH grants HL108307, K24HL093294, CA018029 and CA078902. SS received a fellowship from the Joel Meyers Memorial Fund.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M Mielcarek.

Ethics declarations

Competing interests

MB received research support from Merck and served as a consultant for Merck. All other authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Seo, S., Boeckh, M., Storer, B. et al. The association between donor and recipient statin use and infections after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 50, 444–448 (2015). https://doi.org/10.1038/bmt.2014.279

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2014.279

Search

Quick links