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:

Post-Transplant Events

High-dose corticosteroids with or without etanercept for the treatment of idiopathic pneumonia syndrome after allo-SCT

Bone Marrow Transplantation volume 47, pages 1332–1337 (2012)Cite this article

Subjects

Abstract

Idiopathic Pneumonia Syndrome (IPS) is a common complication after allo-SCT and results in high mortality rates. Conventional treatment for IPS typically includes supportive care and high-dose corticosteroids (CS). Data suggests that TNF-α is important in the pathogenesis of IPS and that the TNF-α inhibitor etanercept may be useful for IPS treatment. We performed a retrospective comparison of consecutive patients treated at our center for IPS with CS only from 1999 to 2003 (group 1, n=22) or CS plus etanercept from 2004 to 2007 (group 2, n=17). In all, 18% of patients in group 1 vs 53% in group 2 were successfully taken off respiratory support and discharged from the hospital (P=0.039). OS was significantly better for recipients of CS plus etanercept (P=0.003). The estimated survival at 28 days and 2 years after IPS was 36.4% (95% CI 17–56%) and 9.1% (95% CI 2–25%) for group 1 and 88.2% (95% CI 61–97%) and 18% (95% CI 4–38%) for group 2, respectively. Our retrospective comparison suggests that the addition of etanercept to CS for IPS improves response rates and OS. However, outcomes remain limited in both groups, highlighting the need for more effective interventions to treat early and late complications of IPS.

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

Figure 1

Similar content being viewed by others

References

  1. Clark JG, Hansen JA, Hertz MI, Parkman R, Jensen L, Peavy HH . NHLBI workshop summary. Idiopathic pneumonia syndrome after bone marrow transplantation. Am Rev Respir Dis 1993; 147 (6 Pt 1): 1601–1606.

    Article  CAS  PubMed  Google Scholar 

  2. Cooke KR, Hill GR, Gerbitz A, Kobzik L, Martin TR, Crawford JM et al. Tumor necrosis factor-alpha neutralization reduces lung injury after experimental allogeneic bone marrow transplantation. Transplantation 2000; 70: 272–279.

    Article  CAS  PubMed  Google Scholar 

  3. Crawford SW, Longton G, Storb R . Acute graft-versus-host disease and the risks for idiopathic pneumonia after marrow transplantation for severe aplastic anemia. Bone Marrow Transplant 1993; 12: 225–231.

    CAS  PubMed  Google Scholar 

  4. Kantrow SP, Hackman RC, Boeckh M, Myerson D, Crawford SW . Idiopathic pneumonia syndrome: changing spectrum of lung injury after marrow transplantation. Transplantation 1997; 63: 1079–1086.

    Article  CAS  PubMed  Google Scholar 

  5. Yanik G, Ho V, Levine J, White E, Braun T, Antin J et al. The impact of soluble tumor necrosis factor receptor etanercept on the treatment of idiopathic pneumonia syndrome after allogeneic hematopoietic stem cell transplantation. Blood 2008; 112: 3073–3081.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Fukuda T, Hackman R, Guthrie K, Sandmaier B, Boeckh M, Maris M et al. Risks and outcomes of idiopathic pneumonia syndrome after nonmyeloablative and conventional conditioning regimens for allogeneic hematopoietic stem cell transplantation. Blood 2003; 102: 2777–2785.

    Article  PubMed  Google Scholar 

  7. Yanik G, Hellerstedt B, Custer J, Hutchinson R, Kwon D, Ferrara JL et al. Etanercept (Enbrel) administration for idiopathic pneumonia syndrome after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2002; 8: 395–400.

    Article  CAS  PubMed  Google Scholar 

  8. Afessa B, Peters S . Noninfectious pneumonitis after blood and marrow transplant. Curr Opin Oncol 2008; 20: 227–233.

    Article  PubMed  Google Scholar 

  9. Keates-Baleeiro J, Moore P, Koyama T, Manes B, Calder C, Frangoul H . Incidence and outcome of idiopathic pneumonia syndrome in pediatric stem cell transplant recipients. Bone Marrow Transplant 2006; 38: 285–289.

    Article  CAS  PubMed  Google Scholar 

  10. Cooke KR, Yanik G . Acute lung injury after allogeneic stem cell transplantation: is the lung a target of acute graft-versus-host disease? Bone Marrow Transplant 2004; 34: 753–765.

    Article  CAS  PubMed  Google Scholar 

  11. Clark JG, Madtes DK, Martin TR, Hackman RC, Farrand AL, Crawford SW . Idiopathic pneumonia after bone marrow transplantation: cytokine activation and lipopolysaccharide amplification in the bronchoalveolar compartment. Crit Care Med 1999; 27: 1800–1806.

    Article  CAS  PubMed  Google Scholar 

  12. Cooke KR, Kobzik L, Martin TR, Brewer J, Delmonte J, Crawford JM et al. An experimental model of idiopathic pneumonia syndrome after bone marrow transplantation: I. The roles of minor H antigens and endotoxin. Blood 1996; 88: 3230–3239.

    CAS  PubMed  Google Scholar 

  13. Piguet PF, Grau GE, Collart MA, Vassalli P, Kapanci Y . Pneumopathies of the graft-versus-host reaction. Alveolitis associated with an increased level of tumor necrosis factor mRNA and chronic interstitial pneumonitis. Lab Invest 1989; 61: 37–45.

    CAS  PubMed  Google Scholar 

  14. Shankar G, Bryson JS, Jennings CD, Kaplan AM, Cohen DA . Idiopathic pneumonia syndrome after allogeneic bone marrow transplantation in mice. Role of pretransplant radiation conditioning. Am J Resp Cell Mol Biol 1999; 20: 1116–1124.

    Article  CAS  Google Scholar 

  15. Carlson M, West M, Coghill J, Panoskaltsis-Mortari A, Blazar B, Serody J . In vitro-differentiated TH17 cells mediate lethal acute graft-versus-host disease with severe cutaneous and pulmonary pathologic manifestations. Blood 2009; 113: 1365–1374.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Yanik GA, Ho VT, Levine JE, White ES, Braun T, Antin JH et al. The impact of soluble tumor necrosis factor receptor etanercept on the treatment of idiopathic pneumonia syndrome after allogeneic hematopoietic stem cell transplantation. Blood 2008; 112: 3073–3081.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Tun HW, Wallace KH, Grinton SF, Khoor A, Burger CD . Etanercept therapy for late-onset idiopathic pneumonia syndrome after nonmyeloablative allogeneic hematopoietic stem cell transplantation. Transplant Proc 2005; 37: 4492–4496.

    Article  CAS  PubMed  Google Scholar 

  18. 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 

  19. Bunin N, Aplenc R, Leahey A, Magira E, Grupp S, Pierson G et al. Outcomes of transplantation with partial T-cell depletion of matched or mismatched unrelated or partially matched related donor bone marrow in children and adolescents with leukemias. Bone Marrow Transplant 2005; 35: 151–158.

    Article  CAS  PubMed  Google Scholar 

  20. Zhu K-E, Hu J-Y, Zhang T, Chen J, Zhong J, Lu Y-H . Incidence, risks, and outcome of idiopathic pneumonia syndrome early after allogeneic hematopoietic stem cell transplantation. Eur J Haematol 2008; 81: 461–466.

    Article  PubMed  Google Scholar 

  21. Yanik G, Cooke K . The lung as a target organ of graft-versus-host disease. Semin Hematol 2006; 43: 42–52.

    Article  PubMed  Google Scholar 

  22. Hildebrandt G, Olkiewicz K, Corrion L, Chang Y, Clouthier S, Liu C et al. Donor-derived TNF-alpha regulates pulmonary chemokine expression and the development of idiopathic pneumonia syndrome after allogeneic bone marrow transplantation. Blood 2004; 104: 586–593.

    Article  CAS  PubMed  Google Scholar 

  23. Frangoul H, Koyama T, Domm J . Etanercept for treatment of idiopathic pneumonia syndrome after allogeneic hematopoietic stem cell transplantation. Blood 2009; 113: 2868–2869; author reply 2869.

    Article  CAS  PubMed  Google Scholar 

  24. Schoenfeld D, Bernard G . Statistical evaluation of ventilator-free days as an efficacy measure in clinical trials of treatments for acute respiratory distress syndrome. Crit Care Med 2002; 30: 1772–1777.

    Article  PubMed  Google Scholar 

  25. Frangoul H, Koyama T, Domm J . Etanercept for treatment of idiopathic pneumonia syndrome after allogeneic hematopoietic stem cell transplantation. Blood 2009; 113: 2868–2869.

    Article  CAS  PubMed  Google Scholar 

  26. Panoskaltsis-Mortari A, Griese M, Madtes DK, Belperio JA, Haddad IY, Folz RJ et al. An Official American Thoracic Society Research Statement: noninfectious lung injury after hematopoietic stem cell transplantation: idiopathic pneumonia syndrome. Am J Respir Crit Care Med 2011; 183: 1262–1279.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Capizzi SA, Kumar S, Huneke NE, Gertz MA, Inwards DJ, Litzow MR et al. Peri-engraftment respiratory distress syndrome during autologous hematopoietic stem cell transplantation. Bone Marrow Transplant 2001; 27: 1299–1303.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported in part by the following grants: NIH K24 CA11787901 (DLP) and University of Pennsylvania Cancer Center Core Grant: P30-CA016520 (DFH, KST)

Author contributions: RT, NF, JD, MV and DLP designed research; RT, NF, JD, MV and DLP performed research; DFH and KST designed the statistical section and performed the statistical analyses; RT and DLP wrote the paper; all authors analyzed data and reviewed and edited the manuscript.

Author information

Author notes

  1. R Tizon

    Present address: Memorial Sloan-Kettering Cancer Center, Division of Hematology-Oncology, Department of Pharmacy,

Authors and Affiliations

  1. Division of Hematology-Oncology, Blood and Marrow Transplant Program, University of Pennsylvania Medical Center, Philadelphia, PA, USA

    R Tizon, N Frey, S C Goldstein, E O Hexner, A Loren, S M Luger, R Reshef, D Tsai, D Vogl, J Davis, M Vozniak, E A Stadtmauer & D L Porter

  2. Department of Biostatistics & Epidemiology, Abramson Cancer Center, University of Pennsylvania Medical Center, Philadelphia, PA, USA

    D F Heitjan & K S Tan

  3. Division of Pulmonary Medicine and Critical Care, University of Pennsylvania Medical Center, Philadelphia, PA, USA

    B Fuchs

Authors
  1. R Tizon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N Frey
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D F Heitjan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K S Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S C Goldstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. E O Hexner
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A Loren
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S M Luger
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. R Reshef
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. D Tsai
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. D Vogl
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. J Davis
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. M Vozniak
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. B Fuchs
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. E A Stadtmauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. D L Porter
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D L Porter.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tizon, R., Frey, N., Heitjan, D. et al. High-dose corticosteroids with or without etanercept for the treatment of idiopathic pneumonia syndrome after allo-SCT. Bone Marrow Transplant 47, 1332–1337 (2012). https://doi.org/10.1038/bmt.2011.260

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2011.260

Keywords

This article is cited by

Search

Advanced search

Quick links