Skip to main content

Advertisement

Log in

Diagnosis and treatment of bronchiolitis obliterans syndrome accessible universally

  • Review Article
  • Published:
Bone Marrow Transplantation Submit manuscript

Abstract

The incidence of bronchiolitis obliterans syndrome (BOS), a devastating manifestation of chronic graft-versus-host-disease, may rise globally due to steady increases in utilization of allogeneic hematopoietic cell transplantation (HCT). Though some advances have occurred in the past decade regarding understanding of the pathogenesis, diagnosis and treatment of BOS, the overall mortality and morbidity remain very high. We sought to determine the current diagnostic and therapeutic challenges, which can potentially hinder optimal management of BOS both in developed and developing countries. We performed a comprehensive systematic review of both modern diagnostic modalities and treatments and then assessed which of them would be universally accessible. The 2014 National Institutes of Health chronic GVHD criteria remains the gold standard tool for diagnosing BOS. Important elements of treatment involve early and accurate detection, as well as utilizing the treatment modalities with known (but variable efficacy) e.g. fluticasone-azithromycin-montelukast [FAM] combination, etanercept, extra-corporeal photopheresis [ECP], lung transplantation, and prompt treatment of complications including infections in sufferers of BOS. Our results indicate that optimum diagnostic tools are not readily available in some parts of the world for early detection, which include a lack of CT scanners, unavailability of pulmonary function testing tools, absence of sub-specialists, lack of certain effective treatments and late referral for lung transplant. We present a systematic review of current literature along with recommendations for available therapies to guide practitioners to optimize the long-term outcomes in HCT survivors regardless of access to experts and expensive therapies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Barker AF, Bergeron A, Rom WN, Hertz MI. Obliterative bronchiolitis. New Engl J Med. 2014;370:1820–8.

    Article  CAS  Google Scholar 

  2. Flowers ME, Apperley JF, Van Besien K, Elmaagacli A, Grigg A, Reddy V, et al. A multicenter prospective phase 2 randomized study of extracorporeal photopheresis for treatment of chronic graft-versus-host disease. Blood. 2008;112:2667–74.

    Article  CAS  Google Scholar 

  3. Sakai R, Kanamori H, Nakaseko C, Yoshiba F, Fujimaki K, Sakura T, et al. Air-leak syndrome following allo-HCT in adult patients: report from the Kanto Study Group for Cell Therapy in Japan. Bone Marrow Transplant. 2011;46:379–84.

    Article  CAS  Google Scholar 

  4. Chien JW, Duncan S, Williams KM, Pavletic SZ. Bronchiolitis obliterans syndrome after allogeneic hematopoietic stem cell transplantation—an increasingly recognized manifestation of chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2010;16:S106–14.

    Article  Google Scholar 

  5. Williams KM. How I treat bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation. Blood. 2017;129:448–55.

    Article  CAS  Google Scholar 

  6. Williams KM, Chien JW, Gladwin MT, Pavletic SZ. Bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation. JAMA. 2009;302:306–14.

    Article  CAS  Google Scholar 

  7. Soubani A, Uberti J. Bronchiolitis obliterans following haematopoietic stem cell transplantation. Eur Respir J. 2007;29:1007–19.

    Article  CAS  Google Scholar 

  8. Niederwieser D, Baldomero H, Szer J, Gratwohl M, Aljurf M, Atsuta Y, et al. Hematopoietic stem cell transplantation activity worldwide in 2012 and a SWOT analysis of the Worldwide Network for Blood and Marrow Transplantation Group including the global survey. Bone Marrow Transplant. 2016;51:778–85.

    Article  CAS  Google Scholar 

  9. Gratwohl A, Baldomero H, Aljurf M, Pasquini MC, Bouzas LF, Yoshimi A, et al. Hematopoietic stem cell transplantation: a global perspective. JAMA. 2010;303:1617–24.

    Article  CAS  Google Scholar 

  10. DUDEK AZ, MAHASETH H, DEFOR TE, WEISDORF DJ. Bronchiolitis obliterans in chronic graft-versus-host disease: analysis of risk factors and treatment outcomes. Biol Blood Marrow Transplant. 2003;9:657–66.

    Article  Google Scholar 

  11. Zaja F, Bacigalupo A, Patriarca F, Stanzani M, Van Lint MT, Fili C, et al. Treatment of refractory chronic GVHD with rituximab: a GITMO study. Bone Marrow Transplant. 2007;40:273–27.

    Article  CAS  Google Scholar 

  12. Kim SJ, Lee JW, Jung CW, Min CK, Cho B, Shin HJ, et al. Weekly rituximab followed by monthly rituximab treatment for steroid-refractory chronic graft-versus-host disease: results from a prospective, multicenter, phase II study. Haematologica. 2010;95:1935–42.

    Article  CAS  Google Scholar 

  13. Lucid CE, Savani BN, Engelhardt BG, Shah P, Clifton C, Greenhut SL, et al. Extracorporeal photopheresis in patients with refractory bronchiolitis obliterans developing after HCT. Bone Marrow Transplant. 2011;46:426–9.

    Article  CAS  Google Scholar 

  14. Del Fante C, Galasso T, Bernasconi P, Scudeller L, Ripamonti F, Perotti C, et al. Extracorporeal photopheresis as a new supportive therapy for bronchiolitis obliterans syndrome after allogeneic stem cell transplantation. Bone Marrow Transplant. 2016;51:728–32.

    Article  Google Scholar 

  15. Child, FJ, Ratnavel, R, Watkins, P, Samson, D, Apperley, J, Ball, J, et al. Extracorporeal photopheresis (ECP) in the treatment of chronic graft-versus-host disease (GVHD). Bone Marrow Transplant; 1999;23:881–7.

    Article  CAS  Google Scholar 

  16. Yanik GA, Mineishi S, Levine JE, Kitko CL, White ES, Vander Lugt MT, et al. Soluble tumor necrosis factor receptor: enbrel (etanercept) for subacute pulmonary dysfunction following allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2012;18:1044–54.

    Article  CAS  Google Scholar 

  17. Lam DCL, Lam B, Wong MK, Lu C, Au WY, Tse EWC, et al. Effects of azithromycin in bronchiolitis obliterans syndrome after HCT—a randomized double-blinded placebo-controlled study. Bone Marrow Transplant. 2011;46:1551–6.

    Article  CAS  Google Scholar 

  18. Khalid M, Al Saghir A, Saleemi S, Al Dammas S, Zeitouni M, Al Mobeireek A, et al. Azithromycin in bronchiolitis obliterans complicating bone marrow transplantation: a preliminary study. Eur Respir J. 2005;25:490–3.

    Article  CAS  Google Scholar 

  19. Norman BC, Jacobsohn DA, Williams KM, Au BKC, Au MA, Lee SJ, et al. Fluticasone, azithromycin and montelukast therapy in reducing corticosteroid exposure in bronchiolitis obliterans syndrome after allogeneic hematopoietic HCT: a case series of eight patients. Bone Marrow Transplant. 2011;46:1369–73.

    Article  CAS  Google Scholar 

  20. Williams KM, Cheng GS, Pusic I, Jagasia M, Burns L, Ho VT, et al. Fluticasone, azithromycin, and montelukast treatment for new-onset bronchiolitis obliterans syndrome after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2016;22:710–6.

    Article  CAS  Google Scholar 

  21. Ratjen F, Rjabko O, Kremens B. High-dose corticosteroid therapy for bronchiolitis obliterans after bone marrow transplantation in children. Bone Marrow Transplant. 2005;36:135.

    Article  CAS  Google Scholar 

  22. Ueda K, Watadani T, Maeda E, Ota S, Kataoka K, Seo S, et al. Outcome and treatment of late-onset noninfectious pulmonary complications after allogeneic HCT. Bone Marrow Transplant. 2010;45:1719–27.

    Article  CAS  Google Scholar 

  23. Holm AM, Riise GC, Hansson L, Brinch L, Bjørtuft Ø, Iversen M, et al. Lung transplantation for bronchiolitis obliterans syndrome after HCT. Bone Marrow Transplant. 2013;48:703–7.

    Article  CAS  Google Scholar 

  24. Chen F, Yamane M, Inoue M, Shiraishi T, Oto T, Minami M, et al. Less maintenance immunosuppression in lung transplantation following hematopoietic stem cell transplantation from the same living donor. Am J Transplant. 2011;11:1509–16.

    Article  CAS  Google Scholar 

  25. Gao, F, Chen, J, Wei, D, Wu, B and Zhou, M. Lung transplantation for bronchiolitis obliterans syndrome after allogenic hematopoietic stem cell transplantation. Fron Med. 2017;12:224–8.

    Article  Google Scholar 

  26. Cheng GS, Campbell AP, Xie H, et al. Correlation and agreement of handheld spirometry with laboratory spirometry in allogeneic hematopoietic cell transplant recipients. Biol Blood Marrow Transplant. 2016;22:925–31.

    Article  Google Scholar 

  27. Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015;21:389–401.

    Article  Google Scholar 

  28. Belloli EA, Degtiar I, Wang X, Yanik GA, Stuckey LJ, Verleden SE, et al. Parametric Response Mapping as an Imaging Biomarker in Lung Transplant Recipients. Am J Respir Crit Care Med. 2017;195:942–52.

    Article  Google Scholar 

  29. Thomas SV, Sarma PS, Alexander M, Pandit L, Shekhar L, Trivedi C, et al. Economic burden of epilepsy in India. Epilepsia. 2001;42:1052–60.

    Article  CAS  Google Scholar 

  30. Palmer J, Williams K, Inamoto Y, Chai X, Martin PJ, Santo Tomas LH, et al. Pulmonary symptoms measured by the national institutes of health lung score predict overall survival, nonrelapse mortality, and patient-reported outcomes in chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2014;20:337–44.

    Article  Google Scholar 

  31. Cooke KR. A “window of opportunity” for patients with late-onset pulmonary dysfunction after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2014;20:291–2.

    Article  Google Scholar 

  32. https://news.aamc.org/medical-education/article/new-aamc-research-reaffirms-looming-physician-shor/ Accessed 08 2017.

  33. Gajewski JL, LeMaistre CF, Silver SM, Lill MC, Selby GB, Horowitz MM, et al. Impending challenges in the hematopoietic stem cell transplantation physician workforce. Biol Blood Marrow Transplant. 2009;15:1493–1501.

    Article  Google Scholar 

  34. Schluger, Neil W, Charles Sherman. Notes from the field. Training pulmonary specialists in a low-income country. 2015;12:467–8.

  35. Majhail NS, Rizzo JD, Lee SJ, Aljurf M, Atsuta Y, Bonfim C, et al. Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation. Hematol/Oncol Stem Cell Ther. 2012;5:1–30.

    Article  CAS  Google Scholar 

  36. Pronovost PJ. Enhancing physicians’ use of clinical guidelines. JAMA. 2013;310:2501–2.

    Article  CAS  Google Scholar 

  37. Best care at lower cost: the path to continuously learning health care in America 2012. Institute of Medicine website, http://www.iom.edu /Reports/2012/Best-Care-at-Lower-Cost-The-Path-to-Continuously-Learning-Heaith-Care-in-America. Accessed 08 2017.

  38. Hashmi S, Carpenter P, Khera N, Tichelli A, Savani BN. Lost in transition: the essential need for long-term follow-up clinic for blood and marrow transplantation survivors. Biol Blood Marrow Transplant. 2015;21:225–32.

    Article  Google Scholar 

  39. Khera N, Chang YH, Hashmi S, Slack J, Beebe T, Roy V, et al. Financial burden in recipients of allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2014;20:1375–81.

    Article  Google Scholar 

  40. Hashmi SK, Bredeson C, Duarte RF, Farnia S, Ferrey S, Fitzhugh C, et al. National Institutes of Health Blood and Marrow Transplant Late Effects Initiative: the Healthcare Delivery Working Group report. Biol Blood Marrow Transplant. 2017;23:717–25.

    Article  Google Scholar 

  41. GS Cheng, AP Campbell, H Xie, Z Correlation and agreement of handheld spirometry with laboratory spirometry in allogeneic hematopoietic cell transplant recipients. BBMT 2016;22:925–31.

    Article  Google Scholar 

  42. Link MP, Hagerty K, Kantarjian HM. Chemotherapy drug shortages in the United States: genesis and potential solutions. J Clin Oncol. 2012;30:692–4.

    Article  Google Scholar 

  43. Metzger ML, Billett A, Link MP. The impact of drug shortages on children with cancer—the example of mechlorethamine. New Engl J Med. 2012;367:2461–3.

    Article  CAS  Google Scholar 

  44. Weill, D, Benden, C, Corris, PA, Dark, JH, Davis, RD, Keshavjee, S 2015. A consensus document for the selection of lung transplant candidates: 2014—an update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation.

  45. Hook JL, Lederer DJ. Selecting lung transplant candidates: where do current guidelines fall short? Expert Rev Respir Med. 2012;6:51–61.

    Article  Google Scholar 

  46. Greer M, Berastegui C, Jaksch P, Benden C, Aubert J, Roux A, et al. Lung transplantation after allogeneic stem cell transplantation: a pan-European experience. Eur Respir J. 2018;51:1701330.

    Article  Google Scholar 

  47. Gadre S, Turowski J, Budev M. Overview of lung transplantation, heart-lung transplantation, liver-lung transplantation, and combined hematopoietic stem cell transplantation and lung transplantation. Clin Chest Med. 2017;38:623–40.

    Article  Google Scholar 

  48. Cheng GS, Edelman JD, Madtes DK, Martin PJ, Flowers ME. Outcomes of lung transplantation after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2014;20:1169–75.

    Article  Google Scholar 

  49. Soubani AO, Kingah P, Alshabani K, Muma G, Haq A. Lung transplantation following hematopoietic stem cell transplantation: report of two cases and systematic review of literature. Clin Transplant. 2014;28:776–82.

    Article  Google Scholar 

Download references

Acknowledgements

Author contribution

AH and SKH wrote the first draft of the manuscript. All authors contributed substantially to the conception, acquisition, analysis, and interpretation of the data for the work and approved the final approval of the version to be published.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shahrukh K. Hashmi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hakim, A., Cooke, K.R., Pavletic, S.Z. et al. Diagnosis and treatment of bronchiolitis obliterans syndrome accessible universally. Bone Marrow Transplant 54, 383–392 (2019). https://doi.org/10.1038/s41409-018-0266-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-018-0266-6

  • Springer Nature Limited

This article is cited by

Navigation