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:

Microbial Issues

Clinical features and outcome of 2009-influenza A (H1N1) after allogeneic hematopoietic SCT

Bone Marrow Transplantation volume 47, pages 236–242 (2012)Cite this article

Abstract

The impact of the 2009 H1N1-Influenza A (H1N1) pandemic in allogeneic hematopoietic SCT recipients (allo-HSCT) is not yet well defined. Between May 2009 and May 2010, all allo-HSCTs who presented with respiratory symptoms were screened for the presence of the H1N1 virus. Oseltamivir resistance was assessed and chart reviews were performed for all cases. In all, 51 of 248 (20%) allo-HSCT recipients followed at our outpatient clinic were screened. We identified 10 patients with H1N1 infection. Close contact with children was the most commonly suspected mode of transmission. Upper and lower respiratory tract infections were present in eight and five patients, respectively. Lymphopenia (<1 G/L) was the most frequent biological abnormality. High immunosuppression was responsible for severe infection requiring mechanical ventilation associated with prolonged viral shedding in three patients who had significant comorbidities and GvHD. Two of them developed an oseltamivir-resistant strain and both patients died subsequently despite intensive therapy, resulting in a case fatality rate of 20%. In conclusion, although most allo-HSCTs had mild symptoms from H1N1 infection, severe immunosuppression and emergence of oseltamivir resistance were likely responsible for a substantial morbidity, further supporting the need for vaccination and monitoring of close contacts, especially children.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Similar content being viewed by others

References

  1. Martino R, Porras RP, Rabella N, Williams JV, Ramila E, Margall N et al. Prospective study of the incidence, clinical features, and outcome of symptomatic upper and lower respiratory tract infections by respiratory viruses in adult recipients of hematopoietic stem cell transplants for hematologic malignancies. Biol Blood Marrow Transplant 2005; 11: 781–796.

    Article  Google Scholar 

  2. Ljungman P, Ward KN, Crooks BN, Parker A, Martino R, Shaw PJ et al. Respiratory virus infections after stem cell transplantation: a prospective study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 2001; 28: 479–484.

    Article  CAS  Google Scholar 

  3. Nichols WG, Guthrie KA, Corey L, Boeckh M . Influenza infections after hematopoietic stem cell transplantation: risk factors, mortality, and the effect of antiviral therapy. Clin Infect Dis 2004; 39: 1300–1306.

    Article  Google Scholar 

  4. Khanna N, Steffen I, Studt JD, Schreiber A, Lehmann T, Weisser M et al. Outcome of influenza infections in outpatients after allogeneic hematopoietic stem cell transplantation. Transpl Infect Dis 2009; 11: 100–105.

    Article  CAS  Google Scholar 

  5. Martino R, Ramila E, Rabella N, Munoz JM, Peyret M, Portos JM et al. Respiratory virus infections in adults with hematologic malignancies: a prospective study. Clin Infect Dis 2003; 36: 1–8.

    Article  Google Scholar 

  6. Garten RJ, Davis CT, Russell CA, Shu B, Lindstrom S, Balish A et al. Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science 2009; 325: 197–201.

    Article  CAS  Google Scholar 

  7. CDC. Outbreak of swine-origin influenza A (H1N1) virus infection—Mexico, March-April 2009. MMWR Morb Mortal Wkly Rep 2009; 58: 467–470.

    Google Scholar 

  8. Bautista E, Chotpitayasunondh T, Gao Z, Harper SA, Shaw M, Uyeki TM et al. Clinical aspects of pandemic 2009 influenza A (H1N1) virus infection. N Engl J Med 2010; 362: 1708–1719.

    Article  Google Scholar 

  9. Cao B, Li XW, Mao Y, Wang J, Lu HZ, Chen YS et al. Clinical features of the initial cases of 2009 pandemic influenza A (H1N1) virus infection in China. N Engl J Med 2009; 361: 2507–2517.

    Article  CAS  Google Scholar 

  10. Jain S, Kamimoto L, Bramley AM, Schmitz AM, Benoit SR, Louie J et al. Hospitalized patients with 2009 H1N1 influenza in the United States, April-June 2009. N Engl J Med 2009; 361: 1935–1944.

    Article  CAS  Google Scholar 

  11. Perez-Padilla R, de la Rosa-Zamboni D, Ponce de Leon S, Hernandez M, Quinones-Falconi F, Bautista E et al. Pneumonia and respiratory failure from swine-origin influenza A (H1N1) in Mexico. N Engl J Med 2009; 361: 680–689.

    Article  CAS  Google Scholar 

  12. Garbino J, Gerbase MW, Wunderli W, Kolarova L, Nicod LP, Rochat T et al. Respiratory viruses and severe lower respiratory tract complications in hospitalized patients. Chest 2004; 125: 1033–1039.

    Article  Google Scholar 

  13. World Health Organization. CDC Protocol of Realtime RT-PCR for Swine Influenza A (H1N1). World Health Organization: Geneva, Accessed 30 November 2009, at http://www.who.int/csr/resources/publications/swineflu/realtimeptpcr/en. 2009.

  14. De la Camara R, Cannata J, Nieto J, Gonzalez-Vicent M, Lassaletta A, Garcia-Noblejas A et al. Novel swine-origin influenza A (H1N1) in SCT and onco-haematological patients: clinical characteristics and outcome in 87 confirmed cases. Bone Marrow Transplant 2010; 45 (suppl 2): S35–S36. (Abstract 224).

    Google Scholar 

  15. Ljungman P . H1N1 Infections In Hematopoietic Stem Cell Transplant Recipients: A Prospective Study, ICAAC Meeting 2010. Abstract.

  16. George B, Ferguson P, Kerridge I, Gilroy N, Gottlieb D, Hertzberg M . The clinical impact of infection with Swine flu (H1N1 09) strain of influenza virus in hematopoietic stem cell transplant recipients. Biol Blood Marrow Transplant 2010; 17: 147–153.

    Article  Google Scholar 

  17. Redelman-Sidi G, Sepkowitz KA, Huang CK, Park S, Stiles J, Eagan J et al. 2009 H1N1 influenza infection in cancer patients and hematopoietic stem cell transplant recipients. J Infect 2010; 60: 257–263.

    Article  Google Scholar 

  18. Taplitz R, Espinosa-Aguilar L, Green J, Forrest G, Ball E, Maziarz R et al. Novel H1N1 influenza in hematopoietic stem cell transplant recipients: two center's experience. Biol Blood Marrow Transplant (e-pub ahead of print 10 August 2010).

  19. Tramontana AR, George B, Hurt AC, Doyle JS, Langan K, Reid AB et al. Oseltamivir resistance in adult oncology and hematology patients infected with pandemic (H1N1) 2009 virus, Australia. Emerg Infect Dis 2010; 16: 1068–1075.

    Article  CAS  Google Scholar 

  20. Chalandon Y, Roosnek E, Mermillod B, Waelchli L, Helg C, Chapuis B . Can only partial T-cell depletion of the graft before hematopoietic stem cell transplantation mitigate graft-versus-host disease while preserving a graft-versus-leukemia reaction? A prospective phase II study. Biol Blood Marrow Transplant 2006; 12: 102–110.

    Article  Google Scholar 

  21. OFSP. Rapport de situation hebdomdaire de l’OFSP. http://www.bag.admin.ch/dokumentation/publikationen/01435/07914/index.html?lang=fr. Accessed online 9 September 2010.

  22. Ljungman P . Solid-organ transplants and the risks of pandemic influenza. Lancet Infect Dis 2010; 10: 506–507.

    Article  Google Scholar 

  23. Dawood FS, Jain S, Finelli L, Shaw MW, Lindstrom S, Garten RJ et al. Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 2009; 360: 2605–2615.

    Article  Google Scholar 

  24. Miller E, Hoschler K, Hardelid P, Stanford E, Andrews N, Zambon M . Incidence of 2009 pandemic influenza A H1N1 infection in England: a cross-sectional serological study. Lancet 2010; 375: 1100–1108.

    Article  Google Scholar 

  25. Cauchemez S, Donnelly CA, Reed C, Ghani AC, Fraser C, Kent CK et al. Household transmission of 2009 pandemic influenza A (H1N1) virus in the United States. N Engl J Med 2009; 361: 2619–2627.

    Article  CAS  Google Scholar 

  26. Kumar D, Michaels MG, Morris MI, Green M, Avery RK, Liu C et al. Outcomes from pandemic influenza A H1N1 infection in recipients of solid-organ transplants: a multicentre cohort study. Lancet Infect Dis 2010; 10: 521–526.

    Article  Google Scholar 

  27. Patel P, Sweiss K, Shatavi S, Peace D, Clark N, Rondelli D . The impact of novel influenza A (H1N1) after hematopoietic SCT. Bone Marrow Transplant 2010; 45: 1756–1757.

    Article  CAS  Google Scholar 

  28. Ditschkowski M, Elmaagacli AH, Beelen DW . H1N1 in allogeneic stem cell recipients: courses of infection and influence of vaccination on graft-versus-host-disease (GVHD). Ann Hematol 2010; 90: 117–118.

    Article  Google Scholar 

  29. Garland P, de Lavallade H, Sekine T, Hoschler K, Sriskandan S, Patel P et al. Humoral and cellular immunity to primary H1N1 infection in patients with hematological malignancies and following stem cell transplantation. Biol Blood Marrow Transplant (e-pub ahead of print 10 August 2010).

  30. CDC. Oseltamivir-resistant novel influenza A (H1N1) virus infection in two immunosuppressed patients—Seattle, Washington, 2009. MMWR Morb Mortal Wkly Rep 2009; 58: 893–896.

    Google Scholar 

  31. Kharfan-Dabaja MA, Velez A, Richards K, Greene JN, Field T, Sandin R . Influenza A/pandemic 2009/H1N1 in the setting of allogeneic hematopoietic cell transplantation: a potentially catastrophic problem in a vulnerable population. Int J Hematol 2010; 91: 124–127.

    Article  Google Scholar 

  32. Rozovski U, Herishanu Y, Gipstein L, Naparstek E . Fatal H1N1 influenza infection in an allo-SCT recipient. Bone Marrow Transplant 2010; 45: 1572–1573.

    Article  CAS  Google Scholar 

  33. Chemaly RF, Ghosh S, Bodey GP, Rohatgi N, Safdar A, Keating MJ et al. Respiratory viral infections in adults with hematologic malignancies and human stem cell transplantation recipients: a retrospective study at a major cancer center. Medicine (Baltimore) 2006; 85: 278–287.

    Article  Google Scholar 

  34. Engelhard D, Nagler A, Hardan I, Morag A, Aker M, Baciu H et al. Antibody response to a two-dose regimen of influenza vaccine in allogeneic T cell-depleted and autologous BMT recipients. Bone Marrow Transplant 1993; 11: 1–5.

    CAS  PubMed  Google Scholar 

  35. Pauksen K, Linde A, Hammarstrom V, Sjolin J, Carneskog J, Jonsson G et al. Granulocyte-macrophage colony-stimulating factor as immunomodulating factor together with influenza vaccination in stem cell transplant patients. Clin Infect Dis 2000; 30: 342–348.

    Article  CAS  Google Scholar 

  36. Avetisyan G, Aschan J, Hassan M, Ljungman P . Evaluation of immune responses to seasonal influenza vaccination in healthy volunteers and in patients after stem cell transplantation. Transplantation 2008; 86: 257–263.

    Article  CAS  Google Scholar 

  37. Plennevaux E, Sheldon E, Blatter M, Reeves-Hoche MK, Denis M . Immune response after a single vaccination against 2009 influenza A H1N1 in USA: a preliminary report of two randomised controlled phase 2 trials. Lancet 2010; 375: 41–48.

    Article  CAS  Google Scholar 

  38. Zaia J, Baden L, Boeckh MJ, Chakrabarti S, Einsele H, Ljungman P et al. Viral disease prevention after hematopoietic cell transplantation. Bone Marrow Transplant 2009; 44: 471–482.

    Article  CAS  Google Scholar 

  39. Ljungman P, Cordonnier C, Einsele H, Englund J, Machado CM, Storek J et al. Vaccination of hematopoietic cell transplant recipients. Bone Marrow Transplant 2009; 44: 521–526.

    Article  CAS  Google Scholar 

  40. Lalayanni C, Sirigou A, Iskas M, Smias C, Sakellari I, Anagnostopoulos A . Outbreak of novel influenza A (H1N1) in an adult haematology department and haematopoietic cell transplantation unit: clinical presentation and outcome. J Infect 2010; 61: 270–272.

    Article  Google Scholar 

  41. Bastos DA, Rodrigues CA, Patah P, Kallas EG, Rocha V, Novis Y . Pandemic influenza A H1N1/09 virus infection in hematopoietic SCT recipient. Bone Marrow Transplant 2010 (e-pub ahead of print 7 June 2010; doi:10.1038/bmt.2010.133).

  42. Frangoul H, Domm J, Denison MR, Calder C, Black J . H1N1 infection mimicking the clinical presentation of gastrointestinal GVHD in a patient following allo-SCT. Bone Marrow Transplant 2010; 46: 152–153.

    Article  Google Scholar 

  43. Campbell AP, Jacob ST, Kuypers J, Wald A, Englund JA, Corey L et al. Respiratory failure caused by 2009 novel influenza A/H1N1 in a hematopoietic stem-cell transplant recipient: detection of extrapulmonary H1N1 RNA and use of intravenous peramivir. Ann Intern Med 2010; 152: 619–620.

    Article  Google Scholar 

Download references

Acknowledgements

We thank our nurse staff of the transplant unit ‘5FL’ and the outpatient clinic ‘polyclinique d’oncologie’ for excellent care given to patients.

Author information

Authors and Affiliations

  1. Division of Hematology, University Hospital, Geneva, Switzerland

    B Mohty, M Vukicevic, M Nagy, E Levrat, M Bernimoulin, E Roosnek, J Passweg & Y Chalandon

  2. Laboratory of Virology, University Hospital, Geneva, Switzerland

    Y Thomas & L Kaiser

  3. Swiss National Centre for Influenza, University Hospital, Geneva, Switzerland

    Y Thomas & L Kaiser

  4. Division of Infectious Diseases, University Hospital, Geneva, Switzerland

    L Kaiser

  5. Division of Hematology, Geneva University Hospital Blood and Marrow Transplant Program, Geneva, Switzerland

    B Mohty, M Vukicevic, M Nagy, E Levrat, M Bernimoulin, E Roosnek, J Passweg & Y Chalandon

Authors
  1. B Mohty
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Vukicevic
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M Nagy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E Levrat
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M Bernimoulin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. L Kaiser
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. E Roosnek
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J Passweg
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Y Chalandon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to B Mohty.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mohty, B., Thomas, Y., Vukicevic, M. et al. Clinical features and outcome of 2009-influenza A (H1N1) after allogeneic hematopoietic SCT. Bone Marrow Transplant 47, 236–242 (2012). https://doi.org/10.1038/bmt.2011.57

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2011.57

Keywords

Search

Advanced search

Quick links