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Bronchiolitis obliterans with allogeneic hematopoietic cell transplantation: a 10-year experience of the Okayama BMT Group

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Abstract

Bronchiolitis obliterans (BO) is a devastating complication of allogeneic hematopoietic stem cell transplantation (HSCT). We retrospectively studied 465 patients who underwent HSCT in the Okayama BMT Group between 2000 and 2009, and describe the detailed clinical features of 13 patients with BO. The 5-year cumulative incidence of BO was 3.43 %. The median time from transplantation to onset of BO was 15 months. In seven of the 13 patients, the primary symptom was only cough, indicating that cough was an important initial symptom for early diagnosis. The median duration from the onset of BO to the requirement of O2 supplementation was 13 months and the main cause of death was respiratory failure. History of chronic graft-versus-host disease was a significant risk factor. Furthermore, female recipients were at greater risk of BO than male recipients; however, no other previously reported risk factors were detected. It is currently difficult to prevent BO on the basis of the reported risk factors. A novel strategy for the early diagnosis and treatment of BO is required.

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References

  1. Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M, et al. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med. 2010;363:2091–101.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Afessa B, Litzow MR, Tefferi A. Bronchiolitis obliterans and other late onset non-infectious pulmonary complications in hematopoietic stem cell transplantation. Bone Marrow Transpl. 2001;28:425–34.

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  4. 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;183:1262–79.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transpl. 2005;11:945–56.

    Article  Google Scholar 

  6. Sanchez J, Torres A, Serrano J, Roman J, Martin C, Perula L, et al. Long-term follow-up of immunosuppressive treatment for obstructive airways disease after allogeneic bone marrow transplantation. Bone Marrow Transpl. 1997;20:403–8.

    Article  CAS  Google Scholar 

  7. Palmas A, Tefferi A, Myers JL, Scott JP, Swensen SJ, Chen MG, et al. Late-onset noninfectious pulmonary complications after allogeneic bone marrow transplantation. Br J Haematol. 1998;100:680–7.

    Article  CAS  PubMed  Google Scholar 

  8. 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 Transpl. 2003;9:657–66.

    Article  Google Scholar 

  9. Yoshihara S, Tateishi U, Ando T, Kunitoh H, Suyama H, Onishi Y, et al. Lower incidence of bronchiolitis obliterans in allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning compared with myeloablative conditioning. Bone Marrow Transpl. 2005;35:1195–200.

    Article  CAS  Google Scholar 

  10. Santo Tomas LH, Loberiza FR Jr, Klein JP, Layde PM, Lipchik RJ, Rizzo JD, et al. Risk factors for bronchiolitis obliterans in allogeneic hematopoietic stem-cell transplantation for leukemia. Chest. 2005;128:153–61.

    Article  PubMed  Google Scholar 

  11. Duncan CN, Buonanno MR, Barry EV, Myers K, Peritz D, Lehmann L. Bronchiolitis obliterans following pediatric allogeneic hematopoietic stem cell transplantation. Bone Marrow Transpl. 2008;41:971–5.

    Article  CAS  Google Scholar 

  12. Nishio N, Yagasaki H, Takahashi Y, Muramatsu H, Hama A, Tanaka M, et al. Late-onset non-infectious pulmonary complications following allogeneic hematopoietic stem cell transplantation in children. Bone Marrow Transpl. 2009;44:303–8.

    Article  CAS  Google Scholar 

  13. Friedrichs B, Tichelli A, Bacigalupo A, Russell NH, Ruutu T, Shapira MY, et al. Long-term outcome and late effects in patients transplanted with mobilised blood or bone marrow: a randomised trial. Lancet Oncol. 2010;11:331–8.

    Article  PubMed  Google Scholar 

  14. Au BK, Au MA, Chien JW. Bronchiolitis obliterans syndrome epidemiology after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transpl. 2011;17:1072–8.

    Article  Google Scholar 

  15. Nakaseko C, Ozawa S, Sakaida E, Sakai M, Kanda Y, Oshima K, et al. Incidence, risk factors and outcomes of bronchiolitis obliterans after allogeneic stem cell transplantation. Int J Hematol. 2011;93:375–82.

    Article  PubMed  Google Scholar 

  16. Chien JW, Martin PJ, Gooley TA, Flowers ME, Heckbert SR, Nichols WG, et al. Airflow obstruction after myeloablative allogeneic hematopoietic stem cell transplantation. Am J Respir Crit Care Med. 2003;168:208–14.

    Article  PubMed  Google Scholar 

  17. Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE, et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980;69:204–17.

    Article  CAS  PubMed  Google Scholar 

  18. Gooley TA, Leisenring W, Crowley J, Storer BE. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med. 1999;18:695–706.

    Article  CAS  PubMed  Google Scholar 

  19. Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509.

    Article  Google Scholar 

  20. Yoshihara S, Yanik G, Cooke KR, Mineishi S. Bronchiolitis obliterans syndrome (BOS), bronchiolitis obliterans organizing pneumonia (BOOP), and other late-onset noninfectious pulmonary complications following allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transpl. 2007;13:749–59.

    Article  Google Scholar 

  21. Hildebrandt GC, Fazekas T, Lawitschka A, Bertz H, Greinix H, Halter J, et al. Diagnosis and treatment of pulmonary chronic GVHD: report from the consensus conference on clinical practice in chronic GVHD. Bone Marrow Transpl. 2011;46:1283–95.

    Article  CAS  Google Scholar 

  22. 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  PubMed  Google Scholar 

  23. Lam DC, Lam B, Wong MK, Lu C, Au WY, Tse EW, et al. Effects of azithromycin in bronchiolitis obliterans syndrome after hematopoietic SCT—a randomized double-blinded placebo-controlled study. Bone Marrow Transpl. 2011;46:1551–6.

    Article  CAS  Google Scholar 

  24. Bashoura L, Gupta S, Jain A, Couriel DR, Komanduri KV, Eapen GA, et al. Inhaled corticosteroids stabilize constrictive bronchiolitis after hematopoietic stem cell transplantation. Bone Marrow Transpl. 2008;41:63–7.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  26. Uhlving HH, Buchvald F, Heilmann CJ, Nielsen KG, Gormsen M, Muller KG. Bronchiolitis obliterans after allo-SCT: clinical criteria and treatment options. Bone Marrow Transpl. 2012;47:1020–9.

    Article  CAS  Google Scholar 

  27. Nakamoto-Matsubara R, Nishikii H, Yamada K, Ito M, Hasegawa Y, Kurita N, et al. Early pathologic findings of bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation: a proposal from a case. Case Report Hematol. 2012;2012:957612.

    Google Scholar 

  28. Nakasone H, Kanda J, Yano S, Atsuta Y, Ago H, Fukuda T, et al. A case–control study of bronchiolitis obliterans syndrome following allogeneic hematopoietic stem cell transplantation. Transpl Int. 2013.

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Acknowledgments

The authors would like to express their appreciation for the contributions of all of the physicians at the institutions of the Okayama BMT Group.

Conflict of interest

The authors report no potential competing conflicts of interest.

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Authors and Affiliations

  1. Department of Hematology and Oncology, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Nobuharu Fujii, Hisakazu Nishimori, Ken-ichi Matsuoka, Eisei Kondo, Yoshinobu Maeda, Katsuji Shinagawa & Mitsune Tanimoto

  2. Division of Hematology, Ehime Prefectural Central Hospital, Ehime, Japan

    Koichi Nakase, Yuichiro Nawa & Masamichi Hara

  3. Department of Hematology, National Hospital Organization Okayama Medical Center, Okayama, Japan

    Shoji Asakura & Kazutaka Sunami

  4. Department of Preventive Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan

    Keitaro Matsuo

  5. Hematology Center, Takanoko Hospital, Ehime, Japan

    Masamichi Hara

Authors
  1. Nobuharu Fujii
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  2. Koichi Nakase
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  3. Shoji Asakura
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  4. Keitaro Matsuo
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  5. Yuichiro Nawa
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  6. Kazutaka Sunami
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  7. Hisakazu Nishimori
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  8. Ken-ichi Matsuoka
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  9. Eisei Kondo
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  10. Yoshinobu Maeda
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  11. Katsuji Shinagawa
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  12. Masamichi Hara
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  13. Mitsune Tanimoto
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Corresponding author

Correspondence to Nobuharu Fujii.

Additional information

From the Okayama Bone Marrow Transplantation Group.

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Fujii, N., Nakase, K., Asakura, S. et al. Bronchiolitis obliterans with allogeneic hematopoietic cell transplantation: a 10-year experience of the Okayama BMT Group. Int J Hematol 99, 644–651 (2014). https://doi.org/10.1007/s12185-014-1556-4

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  • DOI: https://doi.org/10.1007/s12185-014-1556-4

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