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Review

Bronchiolitis obliterans syndrome in adults after allogeneic stem cell transplantation-pathophysiology, diagnostics and treatment

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Pages 553-569 | Received 07 Jun 2016, Accepted 22 Dec 2016, Published online: 17 Jan 2017

References

  • Cornelissen JJ, Gratwohl A, Schlenk RF, et al. The European LeukemiaNet AML working party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach. Nat Rev Clin Oncol. 2012;9(10):579–590.
  • Nakaseko C, Ozawa S, Sakaida E, et al. Incidence, risk factors and outcomes of bronchiolitis obliterans after allogeneic stem cell transplantation. Int J Hematol. 2011;93(3):375–382.
  • Filipovich AH, Weisdorf D, Pavletic S, 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.
  • Hildebrandt GC, Fazekas T, Lawitschka A, et al. Diagnosis and treatment of pulmonary chronic GVHD: report from the consensus conference on clinical practice in chronic GVHD. Bone Marrow Transplant. 2011;46(10):1283–1295.
  • Socie G, Ritz J. Current issues in chronic graft-versus-host disease. Blood. 2014;124(3):374–384.
  • Jagasia MH, Greinix HT, Arora M, 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(3):389-401.e1.
  • Epler GR, Colby TV, McLoud TC, et al. Bronchiolitis obliterans organizing pneumonia. N Engl J Med. 1985;312(3):152–158.
  • Freudenberger TD, Madtes DK, Curtis JR, et al. Association between acute and chronic graft-versus-host disease and bronchiolitis obliterans organizing pneumonia in recipients of hematopoietic stem cell transplants. Blood. 2003;102(10):3822–3828.
  • Gooley TA, Chien JW, Pergam SA, et al. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med. 2010;363(22):2091–2101.
  • Arai S, Arora M, Wang T, et al. Increasing incidence of chronic graft-versus-host disease in allogeneic transplantation: a report from the center for International Blood and Marrow Transplant Research. Biol Blood Marrow Transplant. 2015;21(2):266–274.
  • Holm AM, Riise GC, Hansson L, et al. Lung transplantation for bronchiolitis obliterans syndrome after allo-SCT. Bone Marrow Transplant. 2013;48(5):703–707.
  • Shimabukuro-Vornhagen A, Hallek MJ, Storb RF, et al. The role of B cells in the pathogenesis of graft-versus-host disease. Blood. 2009;114(24):4919–4927.
  • Nakamura R, Forman SJ. Reduced intensity conditioning for allogeneic hematopoietic cell transplantation: considerations for evidence-based GVHD prophylaxis. Expert Rev Hematol. 2014;7(3):407–421.
  • Zeiser R, Blazar BR. Preclinical models of acute and chronic graft-versus-host disease: how predictive are they for a successful clinical translation? Blood. 2016;127(25):3117–3126.
  • Wu T, Young JS, Johnston H, et al. Thymic damage, impaired negative selection, and development of chronic graft-versus-host disease caused by donor CD4+ and CD8+ T cells. J Immunol. 2013;191(1):488–499.
  • Bruggen MC, Klein I, Greinix H, et al. Diverse T-cell responses characterize the different manifestations of cutaneous graft-versus-host disease. Blood. 2014;123(2):290–299.
  • Zorn E, Kim HT, Lee SJ, et al. Reduced frequency of FOXP3+ CD4+CD25+ regulatory T cells in patients with chronic graft-versus-host disease. Blood. 2005;106(8):2903–2911.
  • McDonald-Hyman C, Flynn R, Panoskaltsis-Mortari A, et al. Therapeutic regulatory T-cell adoptive transfer ameliorates established murine chronic GVHD in a CXCR5-dependent manner. Blood. 2016;128(7):1013–1017.
  • Sharma MD, Baban B, Chandler P, et al. Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase. J Clin Invest. 2007;117(9):2570–2582.
  • Sarantopoulos S, Ritz J. Aberrant B-cell homeostasis in chronic GVHD. Blood. 2015;125(11):1703–1707.
  • Miklos DB, Kim HT, Miller KH, et al. Antibody responses to H-Y minor histocompatibility antigens correlate with chronic graft-versus-host disease and disease remission. Blood. 2005;105(7):2973–2978.
  • Svegliati S, Olivieri A, Campelli N, et al. Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease. Blood. 2007;110(1):237–241.
  • Baroni SS, Santillo M, Bevilacqua F, et al. Stimulatory autoantibodies to the PDGF receptor in systemic sclerosis. N Engl J Med. 2006;354(25):2667–2676.
  • Allen JL, Fore MS, Wooten J, et al. B cells from patients with chronic GVHD are activated and primed for survival via BAFF-mediated pathways. Blood. 2012;120(12):2529–2536.
  • Arai S, Sahaf B, Narasimhan B, et al. Prophylactic rituximab after allogeneic transplantation decreases B-cell alloimmunity with low chronic GVHD incidence. Blood. 2012;119(25):6145–6154.
  • Kharfan-Dabaja MA, Mhaskar AR, Djulbegovic B, et al. Efficacy of rituximab in the setting of steroid-refractory chronic graft-versus-host disease: a systematic review and meta-analysis. Biol Blood Marrow Transplant. 2009;15(9):1005–1013.
  • Banovic T, MacDonald KP, Morris ES, et al. TGF-beta in allogeneic stem cell transplantation: friend or foe? Blood. 2005;106(6):2206–2214.
  • Li Q, Zhai Z, Xu X, et al. Decrease of CD4(+)CD25(+) regulatory T cells and TGF-beta at early immune reconstitution is associated to the onset and severity of graft-versus-host disease following allogeneic haematogenesis stem cell transplantation. Leuk Res. 2010;34(9):1158–1168.
  • Zhang L, Mao L, Xu J. Transforming growth factor-beta1 polymorphisms and graft-versus-host disease risk: a meta-analysis. Oncotarget. 2016;7(3):2455–2461.
  • McCormick LL, Zhang Y, Tootell E, et al. Anti-TGF-beta treatment prevents skin and lung fibrosis in murine sclerodermatous graft-versus-host disease: a model for human scleroderma. J Immunol. 1999;163(10):5693–5699.
  • Zerr P, Distler A, Palumbo-Zerr K, et al. Combined inhibition of c-Abl and PDGF receptors for prevention and treatment of murine sclerodermatous chronic graft-versus-host disease. Am J Pathol. 2012;181(5):1672–1680.
  • Chen GL, Arai S, Flowers ME, et al. A phase 1 study of imatinib for corticosteroid-dependent/refractory chronic graft-versus-host disease: response does not correlate with anti-PDGFRA antibodies. Blood. 2011;118(15):4070–4078.
  • Olivieri A, Cimminiello M, Corradini P, et al. Long-term outcome and prospective validation of NIH response criteria in 39 patients receiving imatinib for steroid-refractory chronic GVHD. Blood. 2013;122(25):4111–4118.
  • Schlemmer F, Chevret S, Lorillon G, et al. Late-onset noninfectious interstitial lung disease after allogeneic hematopoietic stem cell transplantation. Respir Med. 2014;108(10):1525–1533.
  • Soubani AO, Pandya CM. The spectrum of noninfectious pulmonary complications following hematopoietic stem cell transplantation. Hematol Oncol Stem Cell Ther. 2010;3(3):143–157.
  • Bhatia S, Francisco L, Carter A, et al. Late mortality after allogeneic hematopoietic cell transplantation and functional status of long-term survivors: report from the bone marrow transplant survivor study. Blood. 2007;110(10):3784–3792.
  • Barker AF, Bergeron A, Rom WN, et al. Obliterative bronchiolitis. N Engl J Med. 2014;370(19):1820–1828.
  • Williams KM, Chien JW, Gladwin MT, et al. Bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation. Jama. 2009;302(3):306–314.
  • Roca J, Granena A, Rodriguez-Roisin R, et al. Fatal airway disease in an adult with chronic graft-versus-host disease. Thorax. 1982;37(1):77–78.
  • Paz HL, Crilley P, Patchefsky A, et al. Bronchiolitis obliterans after autologous bone marrow transplantation. Chest. 1992;101(3):775–778.
  • Frankovich J, Donaldson SS, Lee Y, et al. High-dose therapy and autologous hematopoietic cell transplantation in children with primary refractory and relapsed Hodgkin’s disease: atopy predicts idiopathic diffuse lung injury syndromes. Biol Blood Marrow Transplant. 2001;7(1):49–57.
  • Dudek AZ, Mahaseth H, DeFor TE, et al. Bronchiolitis obliterans in chronic graft-versus-host disease: analysis of risk factors and treatment outcomes. Biol Blood Marrow Transplant. 2003;9(10):657–666.
  • Chien JW, Duncan S, Williams KM, et al. 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(1 Suppl):S106–114.
  • Chien JW. Preventing and managing bronchiolitis obliterans syndrome after allogeneic hematopoietic cell transplantation. Expert Rev Respir Med. 2011;5(1):127–135.
  • Au BK, Au MA, Chien JW. Bronchiolitis obliterans syndrome epidemiology after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2011;17(7):1072–1078.
  • Uhlving HH, Andersen CB, Christensen IJ, et al. Biopsy-verified bronchiolitis obliterans and other noninfectious lung pathologies after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2015;21(3):531–538.
  • Vieira AG, Funke VA, Nunes EC, et al. Bronchiolitis obliterans in patients undergoing allogeneic hematopoietic SCT. Bone Marrow Transplant. 2014;49(6):812–817.
  • Yokoi T, Hirabayashi N, Ito M, et al. Broncho-bronchiolitis obliterans as a complication of bone marrow transplantation: a clinicopathological study of eight autopsy cases. Nagoya BMT Group. Virchows Arch. 1997;431(4):275–282.
  • Biedermann BC, Sahner S, Gregor M, et al. Endothelial injury mediated by cytotoxic T lymphocytes and loss of microvessels in chronic graft versus host disease. Lancet. 2002;359(9323):2078–2083.
  • Penack O, Socie G, van den Brink MR. The importance of neovascularization and its inhibition for allogeneic hematopoietic stem cell transplantation. Blood. 2011;117(16):4181–4189.
  • Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–173.
  • Abbas AK, Murphy KM, Sher A. Functional diversity of helper T lymphocytes. Nature. 1996;383(6603):787–793.
  • Tesmer LA, Lundy SK, Sarkar S, et al. Th17 cells in human disease. Immunol Rev. 2008;223:87–113.
  • Carlson MJ, West ML, Coghill JM, et al. In vitro-differentiated TH17 cells mediate lethal acute graft-versus-host disease with severe cutaneous and pulmonary pathologic manifestations. Blood. 2009;113(6):1365–1374.
  • Sun K, Hsiao HH, Li M, et al. IFN-gamma receptor-deficient donor T cells mediate protection from graft-versus-host disease and preserve graft-versus-tumor responses after allogeneic bone marrow transplantation. J Immunol. 2012;189(4):2033–2042.
  • Yi T, Chen Y, Wang L, et al. Reciprocal differentiation and tissue-specific pathogenesis of Th1, Th2, and Th17 cells in graft-versus-host disease. Blood. 2009;114(14):3101–3112.
  • Rouvier E, Luciani MF, Mattei MG, et al. CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene. J Immunol. 1993;150(12):5445–5456.
  • Fukami N, Ramachandran S, Saini D, et al. Antibodies to MHC class I induce autoimmunity: role in the pathogenesis of chronic rejection. J Immunol. 2009;182(1):309–318.
  • Ohnuma K, Hatano R, Aune TM, et al. Regulation of pulmonary graft-versus-host disease by IL-26+CD26+CD4 T lymphocytes. J Immunol. 2015;194(8):3697–3712.
  • Gowdy KM, Nugent JL, Martinu T, et al. Protective role of T-bet and Th1 cytokines in pulmonary graft-versus-host disease and peribronchiolar fibrosis. Am J Respir Cell Mol Biol. 2012;46(2):249–256.
  • Flynn R, Du J, Veenstra RG, et al. Increased T follicular helper cells and germinal center B cells are required for cGVHD and bronchiolitis obliterans. Blood. 2014;123(25):3988–3998.
  • Reikvam H, Mosevoll KA, Melve GK, et al. The pretransplantation serum cytokine profile in allogeneic stem cell recipients differs from healthy individuals, and various profiles are associated with different risks of posttransplantation complications. Biol Blood Marrow Transplant. 2012;18(2):190–199.
  • Reikvam H, Gronningsaeter IS, Ahmed AB, et al. Metabolic serum profiles for patients receiving allogeneic stem cell transplantation: the pretransplant profile differs for patients with and without posttransplant capillary leak syndrome. Dis Markers. 2015;2015:943430.
  • Reikvam H, Hatfield K, Bruserud Ø. The pretransplant systemic metabolic profile reflects a risk of acute graft versus host disase after allogenic stem celle transplantation. Metabolomics. 2016;12:12.
  • Kittan NA, Hildebrandt GC. The chemokine system: a possible therapeutic target in acute graft versus host disease. Curr Top Microbiol Immunol. 2010;341:97–120.
  • Fantuzzi G. Adiponectin in inflammatory and immune-mediated diseases. Cytokine. 2013;64(1):1–10.
  • Kalderen C, Forsgren M, Karlstrom U, et al. A truncated analogue of CCL2 mediates anti-fibrotic effects on murine fibroblasts independently of CCR2. Biochem Pharmacol. 2012;83(5):644–652.
  • Bouazzaoui A, Spacenko E, Mueller G, et al. Chemokine and chemokine receptor expression analysis in target organs of acute graft-versus-host disease. Genes Immun. 2009;10(8):687–701.
  • Alexander KA, Flynn R, Lineburg KE, et al. CSF-1-dependant donor-derived macrophages mediate chronic graft-versus-host disease. J Clin Invest. 2014;124(10):4266–4280.
  • Lundqvist A, Smith AL, Takahashi Y, et al. Differences in the phenotype, cytokine gene expression profiles, and in vivo alloreactivity of T cells mobilized with plerixafor compared with G-CSF. J Immunol. 2013;191(12):6241–6249.
  • Serody JS, Hill GR. The IL-17 differentiation pathway and its role in transplant outcome. Biol Blood Marrow Transplant. 2012;18(1 Suppl):S56–61.
  • Ito S, Bollard CM, Carlsten M, et al. Ultra-low dose interleukin-2 promotes immune-modulating function of regulatory T cells and natural killer cells in healthy volunteers. Mol Ther. 2014;22(7):1388–1395.
  • Kennedy-Nasser AA, Ku S, Castillo-Caro P, et al. Ultra low-dose IL-2 for GVHD prophylaxis after allogeneic hematopoietic stem cell transplantation mediates expansion of regulatory T cells without diminishing antiviral and antileukemic activity. Clin Cancer Res. 2014;20(8):2215–2225.
  • Sonntag K, Eckert F, Welker C, et al. Chronic graft-versus-host-disease in CD34(+)-humanized NSG mice is associated with human susceptibility HLA haplotypes for autoimmune disease. J Autoimmun. 2015;62:55–66.
  • Uryu H, Hashimoto D, Kato K, et al. alpha-Mannan induces Th17-mediated pulmonary graft-versus-host disease in mice. Blood. 2015;125(19):3014–3023.
  • Coomes SM, Hubbard LL, Moore BB. Impaired pulmonary immunity post-bone marrow transplant. Immunol Res. 2011;50(1):78–86.
  • Wysocki CA, Panoskaltsis-Mortari A, Blazar BR, et al. Leukocyte migration and graft-versus-host disease. Blood. 2005;105(11):4191–4199.
  • Liseth K, Sjo M, Paulsen K, et al. Early pre-engraftment, functional, in vitro responsiveness of T lymphocytes in allotransplanted, acute leukemia patients: proliferation and release of a broad profile of cytokines, possibly predictive of graft-versus-host disease. Eur Cytokine Netw. 2010;21(1):40–49.
  • Henden AS, Hill GR. Cytokines in graft-versus-host disease. J Immunol. 2015;194(10):4604–4612.
  • Gartlan KH, Markey KA, Varelias A, et al. Tc17 cells are a proinflammatory, plastic lineage of pathogenic CD8+ T cells that induce GVHD without antileukemic effects. Blood. 2015;126(13):1609–1620.
  • White DA, Wong PW, Downey R. The utility of open lung biopsy in patients with hematologic malignancies. Am J Respir Crit Care Med. 2000;161(3 Pt 1):723–729.
  • Clark JG, Crawford SW, Madtes DK, et al. Obstructive lung disease after allogeneic marrow transplantation. Clinical presentation and course. Ann Intern Med. 1989;111(5):368–376.
  • Parimon T, Madtes DK, Au DH, et al. Pretransplant lung function, respiratory failure, and mortality after stem cell transplantation. Am J Respir Crit Care Med. 2005;172(3):384–390.
  • Pavletic SZ, Martin P, Lee SJ, et al. Measuring therapeutic response in chronic graft-versus-host disease: National Institutes of Health Consensus Development project on criteria for clinical trials in chronic graft-versus-host disease: IV. Response Criteria Working Group report. Biol Blood Marrow Transplant. 2006;12(3):252–266.
  • Worthy SA, Flint JD, Muller NL. Pulmonary complications after bone marrow transplantation: high-resolution CT and pathologic findings. Radiographics. 1997;17(6):1359–1371.
  • Gunn ML, Godwin JD, Kanne JP, et al. High-resolution CT findings of bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation. J Thorac Imaging. 2008;23(4):244–250.
  • Qualter E, Satwani P, Ricci A, et al. A comparison of bronchoalveolar lavage versus lung biopsy in pediatric recipients after stem cell transplantation. Biol Blood Marrow Transplant. 2014;20(8):1229–1237.
  • Brownback KR, Simpson SQ. Association of bronchoalveolar lavage yield with chest computed tomography findings and symptoms in immunocompromised patients. Ann Thorac Med. 2013;8(3):153–159.
  • Kennedy VE, Todd JL, Palmer SM. Bronchoalveolar lavage as a tool to predict, diagnose and understand bronchiolitis obliterans syndrome. Am J Transplant. 2013;13(3):552–561.
  • Martin WJ 2nd, Smith TF, Sanderson DR, et al. Role of bronchoalveolar lavage in the assessment of opportunistic pulmonary infections: utility and complications. Mayo Clin Proc. 1987;62(7):549–557.
  • Wingard JR, Hiemenz JW, Jantz MA. How I manage pulmonary nodular lesions and nodular infiltrates in patients with hematologic malignancies or undergoing hematopoietic cell transplantation. Blood. 2012;120(9):1791–1800.
  • Chellapandian D, Lehrnbecher T, Phillips B, et al. Bronchoalveolar lavage and lung biopsy in patients with cancer and hematopoietic stem-cell transplantation recipients: a systematic review and meta-analysis. J Clin Oncol. 2015;33(5):501–509.
  • Snyder CL, Ramsay NK, McGlave PB, et al. Diagnostic open-lung biopsy after bone marrow transplantation. J Pediatr Surg. 1990;25(8):871–877.
  • Ferson PF, Landreneau RJ, Dowling RD, et al. Comparison of open versus thoracoscopic lung biopsy for diffuse infiltrative pulmonary disease. J Thorac Cardiovasc Surg. 1993;106(2):194–199.
  • Chamberlain D, Maurer J, Chaparro C, et al. Evaluation of transbronchial lung biopsy specimens in the diagnosis of bronchiolitis obliterans after lung transplantation. J Heart Lung Transplant. 1994;13(6):963–971.
  • Pomerance A, Madden B, Burke MM, et al. Transbronchial biopsy in heart and lung transplantation: clinicopathologic correlations. J Heart Lung Transplant. 1995;14(4):761–773.
  • Clark JG, Schwartz DA, Flournoy N, et al. Risk factors for airflow obstruction in recipients of bone marrow transplants. Ann Iintern Med. 1987;107(5):648–656.
  • Grube M, Holler E, Weber D, et al. Outcome of chronic graft-versus-host disease after allogeneic stem cell transplantation-results from a single-center observational study. Biol Blood Marrow Transplant. 2016;22(10):1781–1791.
  • Anasetti C, Logan BR, Lee SJ, et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. N Engl J Med. 2012;367(16):1487–1496.
  • Kollman C, Howe CW, Anasetti C, et al. Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age. Blood. 2001;98(7):2043–2051.
  • Abedin S, Yanik GA, Braun T, et al. Predictive value of bronchiolitis obliterans syndrome stage 0p in chronic graft-versus-host disease of the lung. Biol Blood Marrow Transplant. 2015;21(6):1127–1131.
  • Styczynski J, Tridello G, Gil L, et al. Impact of donor epstein-barr virus serostatus on the incidence of graft-versus-host disease in patients with acute leukemia after hematopoietic stem-cell transplantation: a study from the acute leukemia and infectious diseases working parties of the European Society for Blood and Marrow Transplantation. J Clin Oncol. 2016;34(19):2212–2220.
  • Erard V, Chien JW, Kim HW, et al. Airflow decline after myeloablative allogeneic hematopoietic cell transplantation: the role of community respiratory viruses. J Infect Dis. 2006;193(12):1619–1625.
  • Bashoura L, Gupta S, Jain A, et al. Inhaled corticosteroids stabilize constrictive bronchiolitis after hematopoietic stem cell transplantation. Bone Marrow Transplant. 2008;41(1):63–67.
  • Bergeron A, Belle A, Chevret S, et al. Combined inhaled steroids and bronchodilatators in obstructive airway disease after allogeneic stem cell transplantation. Bone Marrow Transplant. 2007;39(9):547–553.
  • Bergeron A, Chevret S, Chagnon K, et al. Budesonide/Formoterol for bronchiolitis obliterans after hematopoietic stem cell transplantation. Am J Respir Crit Care Med. 2015;191(11):1242–1249.
  • Ratjen F, Rjabko O, Kremens B. High-dose corticosteroid therapy for bronchiolitis obliterans after bone marrow transplantation in children. Bone Marrow Transplant. 2005;36(2):135–138.
  • Khalid M, Al Saghir A, Saleemi S, et al. Azithromycin in bronchiolitis obliterans complicating bone marrow transplantation: a preliminary study. Eur Respir J. 2005;25(3):490–493.
  • Or R, Gesundheit B, Resnick I, et al. Sparing effect by montelukast treatment for chronic graft versus host disease: a pilot study. Transplantation. 2007;83(5):577–581.
  • Norman BC, Jacobsohn DA, Williams KM, 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. 2011;46(10):1369–1373.
  • Williams KM, Cheng GS, Pusic I, et al. Fluticasone, azithromycin, and montelukast treatment for new-onset bronchiolitis obliterans syndrome after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2016;22(4):710–716.
  • Couriel DR, Hosing C, Saliba R, et al. Extracorporeal photochemotherapy for the treatment of steroid-resistant chronic GVHD. Blood. 2006;107(8):3074–3080.
  • Lucid CE, Savani BN, Engelhardt BG, et al. Extracorporeal photopheresis in patients with refractory bronchiolitis obliterans developing after allo-SCT. Bone Marrow Transplant. 2011;46(3):426–429.
  • del Fante C, Galasso T, Bernasconi P, et al. Extracorporeal photopheresis as a new supportive therapy for bronchiolitis obliterans syndrome after allogeneic stem cell transplantation. Bone Marrow Transplant. 2016;51(5):728–731.
  • Fullmer JJ, Fan LL, Dishop MK, et al. Successful treatment of bronchiolitis obliterans in a bone marrow transplant patient with tumor necrosis factor-alpha blockade. Pediatrics. 2005;116(3):767–770.
  • Chiang KY, Abhyankar S, Bridges K, et al. Recombinant human tumor necrosis factor receptor fusion protein as complementary treatment for chronic graft-versus-host disease. Transplantation. 2002;73(4):665–667.
  • Olivieri A, Locatelli F, Zecca M, et al. Imatinib for refractory chronic graft-versus-host disease with fibrotic features. Blood. 2009;114(3):709–718.
  • Watanabe S, Waseda Y, Kimura H, et al. Imatinib for bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2015;50(9):1250–1252.
  • Stadler M, Ahlborn R, Kamal H, et al. Limited efficacy of imatinib in severe pulmonary chronic graft-versus-host disease. Blood. 2009;114(17):3718-3719;author reply 3719-3720.
  • Devillier R, Castagna L, Gonzague L, et al. TLI in refractory chronic GVHD. Bone Marrow Transplant. 2013;48(6):854–858.
  • Jacobsohn DA, Chen AR, Zahurak M, et al. Phase II study of pentostatin in patients with corticosteroid-refractory chronic graft-versus-host disease. J Clin Oncol. 2007;25(27):4255–4261.
  • Zeiser R, Burchert A, Lengerke C, et al. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia. 2015;29(10):2062–2068.
  • Khoury HJ, Kota V, Arellano M, et al. Ruxolitinib as sparing agent for steroid-dependent chronic graft-versus-host disease (cGVHD). Blood. 2015;126(23):1938–1938.
  • Cheng GS, Edelman JD, Madtes DK, et al. Outcomes of lung transplantation after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2014;20(8):1169–1175.
  • Vogl UM, Nagayama K, Bojic M, et al. Lung transplantation for bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation: a single-center experience. Transplantation. 2013;95(4):623–628.
  • Soubani AO, Kingah P, Alshabani K, et al. Lung transplantation following hematopoietic stem cell transplantation: report of two cases and systematic review of literature. Clin Transplant. 2014;28(7):776–782.
  • Sullivan KM, Shulman HM, Storb R, et al. Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression. Blood. 1981;57(2):267–276.
  • Lee SJ, Flowers ME. Recognizing and managing chronic graft-versus-host disease. Hematology Am Soc Hematol Educ Program. 2008;134–141.
  • Jabs K, Sullivan EK, Avner ED, et al. Alternate-day steroid dosing improves growth without adversely affecting graft survival or long-term graft function. A report of the North American pediatric renal transplant cooperative study. Transplantation. 1996;61(1):31–36.
  • Stewart BL, Storer B, Storek J, et al. Duration of immunosuppressive treatment for chronic graft-versus-host disease. Blood. 2004;104(12):3501–3506.
  • Sullivan KM, Witherspoon RP, Storb R, et al. Prednisone and azathioprine compared with prednisone and placebo for treatment of chronic graft-v-host disease: prognostic influence of prolonged thrombocytopenia after allogeneic marrow transplantation. Blood. 1988;72(2):546–554.
  • Martin PJ, Storer BE, Rowley SD, et al. Evaluation of mycophenolate mofetil for initial treatment of chronic graft-versus-host disease. Blood. 2009;113(21):5074–5082.
  • Gilman AL, Schultz KR, Goldman FD, et al. Randomized trial of hydroxychloroquine for newly diagnosed chronic graft-versus-host disease in children: a Children’s Oncology Group Study. Biol Blood Marrow Transplant. 2012;18(1):84–91.
  • Flowers ME, Martin PJ. Evaluation of thalidomide for treatment or prevention of chronic graft-versus-host disease. Leuk Lymphoma. 2003;44(7):1141–1146.
  • Koc S, Leisenring W, Flowers ME, et al. Therapy for chronic graft-versus-host disease: a randomized trial comparing cyclosporine plus prednisone versus prednisone alone. Blood. 2002;100(1):48–51.
  • Gottlieb J, Szangolies J, Koehnlein T, et al. Long-term azithromycin for bronchiolitis obliterans syndrome after lung transplantation. Transplantation. 2008;85(1):36–41.
  • Yates B, Murphy DM, Forrest IA, et al. Azithromycin reverses airflow obstruction in established bronchiolitis obliterans syndrome. Am J Respir Crit Care Med. 2005;172(6):772–775.
  • Gerhardt SG, McDyer JF, Girgis RE, et al. Maintenance azithromycin therapy for bronchiolitis obliterans syndrome: results of a pilot study. Am J Respir Crit Care Med. 2003;168(1):121–125.
  • Vos R, Vanaudenaerde BM, Ottevaere A, et al. Long-term azithromycin therapy for bronchiolitis obliterans syndrome: divide and conquer? J Heart Lung Transplant. 2010;29(12):1358–1368.
  • Chien JW, Martin PJ, Gooley TA, et al. Airflow obstruction after myeloablative allogeneic hematopoietic stem cell transplantation. Am J Respir Crit Care Med. 2003;168(2):208–214.
  • Pidala J, Kim J, Betts BC, et al. Ofatumumab in combination with glucocorticoids for primary therapy of chronic graft-versus-host disease: phase I trial results. Biol Blood Marrow Transplant. 2015;21(6):1074–1082.
  • Herrera AF, Kim HT, Bindra B, et al. A phase II study of bortezomib plus prednisone for initial therapy of chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2014;20(11):1737–1743.
  • Wolf D, von Lilienfeld-Toal M, Wolf AM, et al. Novel treatment concepts for graft-versus-host disease. Blood. 2012;119(1):16–25.
  • Jacobsohn DA, Schechter T, Seshadri R, et al. Eosinophilia correlates with the presence or development of chronic graft-versus-host disease in children. Transplantation. 2004;77(7):1096–1100.
  • Verleden GM, Verleden SE, Vos R, et al. Montelukast for bronchiolitis obliterans syndrome after lung transplantation: a pilot study. Transpl Int. 2011;24(7):651–656.
  • Majhail NS, Schiffer CA, Weisdorf DJ. Improvement of pulmonary function with imatinib mesylate in bronchiolitis obliterans following allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2006;12(7):789–791.
  • Wolff D, Schleuning M, von harsdorf S, et al. Consensus conference on clinical practice in chronic GVHD: second-line treatment of chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2011;17(1):1–17.
  • Celik MR, Lederer DJ, Wilt J, et al. Tacrolimus and azathioprine versus cyclosporine and mycophenolate mofetil after lung transplantation: a retrospective cohort study. J Heart Lung Transplant. 2009;28(7):697–703.
  • Cairn J, Yek T, Banner NR, et al. Time-related changes in pulmonary function after conversion to tacrolimus in bronchiolitis obliterans syndrome. J Heart Lung Transplant. 2003;22(1):50–57.
  • Borro JM, Bravo C, Sole A, et al. Conversion from cyclosporine to tacrolimus stabilizes the course of lung function in lung transplant recipients with bronchiolitis obliterans syndrome. Transplant Proc. 2007;39(7):2416–2419.
  • Snell GI, Valentine VG, Vitulo P, et al. Everolimus versus azathioprine in maintenance lung transplant recipients: an international, randomized, double-blind clinical trial. Am J Transplant. 2006;6(1):169–177.
  • Groetzner J, Wittwer T, Kaczmarek I, et al. Conversion to sirolimus and mycophenolate can attenuate the progression of bronchiolitis obliterans syndrome and improves renal function after lung transplantation. Transplantation. 2006;81(3):355–360.
  • Hernandez RL, Gil PU, Gallo CG, et al. Rapamycin in lung transplantation. Transplant Proc. 2005;37(9):3999–4000.
  • Carnevale-Schianca F, Martin P, Sullivan K, et al. Changing from cyclosporine to tacrolimus as salvage therapy for chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2000;6(6):613–620.
  • Tzakis AG, Abu-Elmagd K, Fung JJ, et al. FK 506 rescue in chronic graft-versus-host-disease after bone marrow transplantation. Transplant Proc. 1991;23(6):3225–3227.
  • Couriel DR, Saliba R, Escalon MP, et al. Sirolimus in combination with tacrolimus and corticosteroids for the treatment of resistant chronic graft-versus-host disease. Br J Haematol. 2005;130(3):409–417.
  • Klink A, Schilling K, Rapp K, et al. High overall response rate in calcineurin inhibitor-free treatment with the mtor inhibitor everolimus in advanced extensive chronic GvHD after allogeneic stem cell transplantation. Blood. 2008;112(11):2210–2210.
  • Busca A, Locatelli F, Marmont F, et al. Response to mycophenolate mofetil therapy in refractory chronic graft-versus-host disease. Haematologica. 2003;88(7):837–839.
  • Bruserud O, Tvedt TH, Paulsen PQ, et al. Extracorporeal photopheresis (photochemotherapy) in the treatment of acute and chronic graft versus host disease: immunological mechanisms and the results from clinical studies. Cancer Immunol Immunother. 2014;63(8):757–777.
  • Fisher AJ, Rutherford RM, Bozzino J, et al. The safety and efficacy of total lymphoid irradiation in progressive bronchiolitis obliterans syndrome after lung transplantation. Am J Transplant. 2005;5(3):537–543.
  • Bullorsky EO, Shanley CM, Stemmelin GR, et al. Total lymphoid irradiation for treatment of drug resistant chronic GVHD. Bone Marrow Transplant. 1993;11(1):75–76.
  • Groves S, Galazka M, Johnson B, et al. Inhaled cyclosporine and pulmonary function in lung transplant recipients. J Aerosol Med Pulm Drug Deliv. 2010;23(1):31–39.
  • Hayes D Jr., Zwischenberger JB, Mansour HM. Aerosolized tacrolimus: a case report in a lung transplant recipient. Transplant Proc. 2010;42(9):3876–3879.
  • Pechet TV, de le Morena M, Mendeloff EN, et al. Lung transplantation in children following treatment for malignancy. J Heart Lung Transplant. 2003;22(2):154–160.
  • Rabitsch W, Deviatko E, Keil F, et al. Successful lung transplantation for bronchiolitis obliterans after allogeneic marrow transplantation. Transplantation. 2001;71(9):1341–1343.
  • Shulman HM, Cardona DM, Greenson JK, et al. NIH consensus development project on criteria for clinical trials in chronic graft-versus-host disease: II. The 2014 Pathology Working Group report. Biol Blood Marrow Transplant. 2015;21(4):589–603.

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