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Post-Transplant Events

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 Transplantation volume 46, pages 1369–1373 (2011)Cite this article

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Abstract

Bronchiolitis obliterans syndrome (BOS) is a devastating pulmonary complication affecting long-term survivors of allogeneic hematopoietic cell transplantation. Treatment of BOS with prolonged courses of high dose corticosteroids is often associated with significant morbidity. Reducing the exposure to corticosteroids may reduce treatment-related morbidity. Our institution has recently begun to treat patients with emerging therapies in an effort to diminish corticosteroid exposure. We retrospectively reviewed the 6-month corticosteroid exposure, lung function and failure rates in eight patients with newly diagnosed BOS who were treated with a combination of fluticasone, azithromycin and montelukast (FAM) and a rapid corticosteroid taper. These patients were compared with 14 matched historical patients who received high-dose corticosteroids, followed by a standard taper. The median 6-month prednisone exposure in FAM-treated patients was 1819 mg (0–4036 mg) compared with 7163 mg (6551–7829 mg) in the control group (P=0.002). The median forced expiratory volume in 1 s (FEV1) change in FAM-treated patients was 2% (−3 to 4%] compared with 1% (−4 to 5%) in the control group (P=1.0). Prednisone exposure in FAM patients was one quarter that of a retrospective-matched group of patients, with minimal change in median FEV1, suggesting that BOS may be spared of the morbidities associated with long-term corticosteroid use by using alternative agents with less side effects.

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References

  1. Holland HK, Wingard JR, Beschorner WE, Saral R, Santos GW . Bronchiolitis obliterans in bone marrow transplantation and its relationship to chronic graft-v-host disease and low serum IgG. Blood 1988; 72: 621–627.

    CAS  PubMed  Google Scholar 

  2. Clark JG, Crawford SW, Madtes DK, Sullivan KM . Obstructive lung disease after allogeneic bone marrow transplantation. Clinical presentation and course. Ann Intern Med 1989; 111: 368–376.

    Article  CAS  PubMed  Google Scholar 

  3. Dudek AZ, Mahaseth H, Defor TE, Weisdorf DJ . Bronciolitis obliterans in chronic graft-versus-host disease: analysis of risk factors and treatment outcomes. Biol Blood Marrow Transplant 2003; 9: 657–666.

    Article  PubMed  Google Scholar 

  4. Santo Tomas LH, Loberiza Jr FR, 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: 153–161.

    Article  PubMed  Google Scholar 

  5. Chan CK, Hyland RH, Hutcheon MA, Minden MD, Alexander MA, Kossakowaska AE et al. Small-airways disease in recipients of allogeneic bone marrow transplants.An analysis of 11 cases and a review of the literature. Medicine (Baltimore) 1987; 66: 327–340.

    Article  CAS  Google Scholar 

  6. Philit F, Wiesendanger T, Archimbaud E, Mornex JF, Brune J, Cordier JF . Post-transplant obstructive lung disease (‘bronchiolitis obliterans’): a clinical comparative study of bone marrow and lung transplant patients. Eur Respir J 1995; 8: 551–558.

    CAS  PubMed  Google Scholar 

  7. 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: 657–666.

    Article  PubMed  Google Scholar 

  8. Van Staa TP, Leufkens HGM, Cooper C . The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int 2002; 13: 777–787.

    Article  CAS  PubMed  Google Scholar 

  9. Fardet L, Kassar A, Cabane J, Flahault A . Corticosteroid-induced adverse events in adults: frequency, screening and prevention. Drug Saf 2007; 30: 861–881.

    Article  CAS  PubMed  Google Scholar 

  10. Majhail NS, Challa TR, Mulrooney DA, Baker KS, Burns LJ . Hypertension and diabetes mellitus in adult and pediatric survivors of allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2009; 15: 1100–1107.

    Article  CAS  PubMed  Google Scholar 

  11. Clore JN, Thurby-Hay L . Glucocorticoid-induced hyperglycemia. Endocr Pract 2009; 15: 469–474.

    Article  PubMed  Google Scholar 

  12. McDonough AK, Curtis JR, Saag KG . The epidemiology of glucocorticoid-associated adverse events. Curr Opin Rheumatol 2008; 20: 131–137.

    Article  PubMed  Google Scholar 

  13. Griffith LM, Pavletic SZ, Lee SJ, Martin PJ, Schultz KR, Vogelsang GB . Chronic graft-versus-host disease--implementation of the National Institutes of Health Consensus Criteria for Clinical Trials. Biol Blood Marrow Transplant 2008; 14: 379–384.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Lee SJ, Flowers ME . Recognizing and managing chronic graft-versus-host disease. Hematology Am Soc Hematol Educ Program 2008, 134–141.

    Article  Google Scholar 

  15. Crapo RO, Morris AH, Gardner RM . Reference spirometric values using techniques and equipment that meet ATS recommendations. Am Rev Respir Dis 1981; 123: 659–664.

    CAS  PubMed  Google Scholar 

  16. Hsu KH, Jenkins DE, Hsi BP, Bourhofer E, Thompson V, Tanawaka N et al. Ventilatory functions of normal children and young adults--Mexican-American, white, and black. I Spirometry J Pediatr 1979; 95: 14–23.

    CAS  PubMed  Google Scholar 

  17. 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 Transplant 2005; 11: 945–956.

    Article  PubMed  Google Scholar 

  18. Chien JW, Martin PJ, Gooley TA, Flowers ME, Heckber SR, Nichols WG et al. Airflow obstruction after myeloablative allogeneic hematopoietic stem cell transplantation. Am J Respir Crit Care Med 2003; 168: 208–214.

    Article  PubMed  Google Scholar 

  19. Bergeron A, Belle A, Chevret S, Ribdbaud P, Devergie A, Esperou H et al. Combined inhaled steroids and bronchodilators in obstructive airway disease after allogeneic stem cell transplantation. Bone Marrow Transplant 2007; 39: 547–553.

    Article  CAS  PubMed  Google Scholar 

  20. 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 Transplant 2008; 41: 63–67.

    Article  CAS  PubMed  Google Scholar 

  21. Khalid M, Saghir Al, 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: 490–493.

    Article  CAS  PubMed  Google Scholar 

  22. Medoff BD, Seung E, Wain JC, Means TK, Campanella GS, Islam SA et al. BLT-1-mediated T cell trafficking is critical for rejection and obliterative bronchiolitis after lung transplantation. J Exp Med 2005; 202: 97–110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wilborn J, Bailie M, Coffey M, Burdick M, Strieter R, Peters-Golden M . Constitutive activation of 5-lipoxygenase in the lungs of patients with idiopathic pulmonary fibrosis. J Clin Invest 1996; 97: 1827–1836.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Or R, Gesundheit B, Resnick I, Bitan M, Avraham A, Avgil M et al. Sparing effect by montelukast treatment for chronic graft versus host disease: a pilot study. Transplantation 2007; 83: 577–581.

    Article  PubMed  Google Scholar 

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Acknowledgements

Financial disclosure: This work was supported in part by the National Institutes of Health Grants HL088201 and AI083028.

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Authors and Affiliations

  1. Department of Medicine, University of Washington Affiliated Hospitals, Seattle, WA, USA

    B C Norman

  2. Stem Cell Transplant Program, Northwestern University School of Medicine, Chicago, IL, USA

    D A Jacobsohn

  3. Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    K M Williams

  4. John A Burns School of Medicine, University of Hawaii, Honolulu, HI, USA

    B K C Au

  5. Department of Epidemiology, Cancer Research Center, University of Hawaii, Honolulu, HI, USA

    M A Au

  6. Clinical Research Division, Fred Hutchison Cancer Research Center, Seattle, WA, USA

    S J Lee, C K Moravec & J W Chien

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  1. B C Norman
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Correspondence to J W Chien.

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Norman, B., Jacobsohn, D., Williams, K. 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 Transplant 46, 1369–1373 (2011). https://doi.org/10.1038/bmt.2010.311

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