Fluticasone, azithromycin and montelukast therapy in reducing corticosteroid exposure in bronchiolitis obliterans syndrome after allogeneic hematopoietic SCT: a case series of eight patients

B C Norman, D A Jacobsohn, K M Williams, B K C Au, M A Au, S J Lee, C K Moravec, J W Chien, B C Norman, D A Jacobsohn, K M Williams, B K C Au, M A Au, S J Lee, C K Moravec, J W Chien

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 (FEV(1)) 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 FEV(1), suggesting that BOS may be spared of the morbidities associated with long-term corticosteroid use by using alternative agents with less side effects.

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(2):621–627.
    1. 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(5):368–376.
    1. 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(10):657–666.
    1. 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(1):153–161.
    1. 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(5):327–340.
    1. 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(4):551–558.
    1. 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. 9(10):657.
    1. Van Staa TP, Leufkens HGM, Cooper C. The Epidemiology of Corticosteroid-Induced Osteoporosis: a Meta-analysis. Osteoporos Int. 2002;13:777–787.
    1. Fardet L, Kassar A, Cabane J, Flahault A. Corticosteroid-Induced Adverse Events in Adults: Frequency, Screening and Prevention. Drug Safety. 2007;30(10):861–881.
    1. 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 Sep;15(9):1100–1107.
    1. Clore JN, Thurby-Hay L. Glucocorticoid-induced hyperglycemia. Endocr Pract. 2009 Jul-Aug;15(5):469–474.
    1. McDonough AK, Curtis JR, Saag KG. The epidemiology of glucocorticoid-associated adverse events. Curr Opin Rheumatol. 2008 Mar;20(2):131–137.
    1. 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 Apr;14(4):379–384.
    1. Lee SJ, Flowers ME. Recognizing and managing chronic graft-versus-host disease. Hematology Am Soc Hematol Educ Program. 2008:134–141.
    1. Crapo RO, Morris AH, Gardner RM. Reference spirometric values using techniques and equipment that meet ATS recommendations. Am Rev Respir Dis. 1981;123(6):659–664.
    1. 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(1):14–23.
    1. 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(12):945–956.
    1. 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(2):208.
    1. 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(9):547–553.
    1. 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(1):63–67.
    1. Khalid M, Al Saghir, 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(3):490–493.
    1. 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(1):97–110.
    1. 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(8):1827–1836.
    1. 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(5):577–581.

Source: PubMed

3
Sottoscrivi