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Bronchiolitis obliterans after allo-SCT: clinical criteria and treatment options

Bone Marrow Transplantation volume 47, pages 1020–1029 (2012)Cite this article

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Abstract

Bronchiolitis obliterans (BO) following allogeneic haematopoietic SCT (HSCT) is a serious complication affecting 1.7–26% of the patients, with a reported mortality rate of 21–100%. It is considered a manifestation of chronic graft-versus-host disease, but our knowledge of aetiology and pathogenesis is still limited. Diagnostic criteria are being developed, and will allow more uniform and comparable research activities between centres. At present, no randomised controlled trials have been completed that could demonstrate an effective treatment. Steroids in combination with other immunosuppressive drugs still constitute the backbone of the treatment strategy, and results from our and other centres suggest that monthly infusions of high-dose pulse i.v. methylprednisolone (HDPM) might stabilise the disease and hinder progression. This article provides an overview of the current evidence regarding treatment options for BO and presents the treatment results with HDPM in a paediatric national HSCT-cohort.

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References

  1. 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 (Suppl 1): S106–S114.

    PubMed  Google Scholar 

  2. 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.

    PubMed  Google Scholar 

  3. 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: 375–382.

    PubMed  Google Scholar 

  4. 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 Transplant 2009; 44: 303–308.

    CAS  PubMed  Google Scholar 

  5. Sakaida E, Nakaseko C, Harima A, Yokota A, Cho R, Saito Y et al. Late-onset noninfectious pulmonary complications after allogeneic stem cell transplantation are significantly associated with chronic graft-versus-host disease and with the graft-versus-leukemia effect. Blood 2003; 102: 4236–4242.

    CAS  PubMed  Google Scholar 

  6. 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 

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

    CAS  PubMed  Google Scholar 

  8. Schultz KR, Green GJ, Wensley D, Sargent MA, Magee JF, Spinelli JJ et al. Obstructive lung disease in children after allogeneic bone marrow transplantation. Blood 1994; 84: 3212–3220.

    CAS  PubMed  Google Scholar 

  9. 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.

    PubMed  Google Scholar 

  10. 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: 208–214.

    PubMed  Google Scholar 

  11. Williams KM, Chien JW, Gladwin MT, Pavletic SZ . Bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation. JAMA 2009; 302: 306–314.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 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.

    PubMed  Google Scholar 

  13. Lee SJ, Vogelsang G, Flowers ME . Chronic graft-versus-host disease. Biol Blood Marrow Transplant 2003; 9: 215–233.

    Article  CAS  PubMed  Google Scholar 

  14. Sullivan KM, Shulman HM, Storb R, Weiden PL, Witherspoon RP, McDonald GB et al. Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression. Blood 1981; 57: 267–276.

    CAS  PubMed  Google Scholar 

  15. Sullivan KM, Agura E, Anasetti C, Appelbaum F, Badger C, Bearman S et al. Chronic graft-versus-host disease and other late complications of bone marrow transplantation. Semin Hematol 1991; 28: 250–259.

    CAS  PubMed  Google Scholar 

  16. Akpek G, Zahurak ML, Piantadosi S, Margolis J, Doherty J, Davidson R et al. Development of a prognostic model for grading chronic graft-versus-host disease. Blood 2001; 97: 1219–1226.

    CAS  PubMed  Google Scholar 

  17. 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 

  18. Schulman LL, Weinberg AD, McGregor CC, Suciu-Foca NM, Itescu S . Influence of donor and recipient HLA locus mismatching on development of obliterative bronchiolitis after lung transplantation. Am J Respir Crit Care Med 2001; 163: 437–442.

    CAS  PubMed  Google Scholar 

  19. Schwarer AP, Hughes JM, Trotman-Dickenson B, Krausz T, Goldman JM . A chronic pulmonary syndrome associated with graft-versus-host disease after allogeneic marrow transplantation. Transplantation 1992; 54: 1002–1008.

    CAS  PubMed  Google Scholar 

  20. Clark JG, Schwartz DA, Flournoy N, Sullivan KM, Crawford SW, Thomas ED . Risk factors for airflow obstruction in recipients of bone marrow transplants. Ann Intern Med 1987; 107: 648–656.

    CAS  PubMed  Google Scholar 

  21. 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: 680–687.

    CAS  PubMed  Google Scholar 

  22. Duncan CN, Buonanno MR, Barry EV, Myers K, Peritz D, Lehmann L . Bronchiolitis obliterans following pediatric allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2008; 41: 971–975.

    CAS  PubMed  Google Scholar 

  23. Ditschkowski M, Elmaagacli AH, Trenschel R, Peceny R, Koldehoff M, Schulte C et al. T-cell depletion prevents from bronchiolitis obliterans and bronchiolitis obliterans with organizing pneumonia after allogeneic hematopoietic stem cell transplantation with related donors. Haematologica 2007; 92: 558–561.

    PubMed  Google Scholar 

  24. Ringden O, Remberger M, Ruutu T, Nikoskelainen J, Volin L, Vindelov L et al. Increased risk of chronic graft-versus-host disease, obstructive bronchiolitis, and alopecia with busulfan versus total body irradiation: long-term results of a randomized trial in allogeneic marrow recipients with leukemia. Nordic Bone Marrow Transplantation Group. Blood 1999; 93: 2196–2201.

    CAS  PubMed  Google Scholar 

  25. Bruno B, Souillet G, Bertrand Y, Werck-Gallois MC, So SA, Bellon G . Effects of allogeneic bone marrow transplantation on pulmonary function in 80 children in a single paediatric centre. Bone Marrow Transplant 2004; 34: 143–147.

    CAS  PubMed  Google Scholar 

  26. Marras TK, Chan CK, Lipton JH, Messner HA, Szalai JP, Laupacis A . Long-term pulmonary function abnormalities and survival after allogeneic marrow transplantation. Bone Marrow Transplant 2004; 33: 509–517.

    CAS  PubMed  Google Scholar 

  27. 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 Transplant 2005; 35: 1195–1200.

    CAS  PubMed  Google Scholar 

  28. Yousem SA . The histological spectrum of pulmonary graft-versus-host disease in bone marrow transplant recipients. Hum Pathol 1995; 26: 668–675.

    CAS  PubMed  Google Scholar 

  29. Shulman HM, Kleiner D, Lee SJ, Morton T, Pavletic SZ, Farmer E et al. Histopathologic diagnosis of chronic graft-versus-host disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: II. Pathology Working Group Report. Biol Blood Marrow Transplant 2006; 12: 31–47.

    PubMed  Google Scholar 

  30. Estenne M, Maurer JR, Boehler A, Egan JJ, Frost A, Hertz M et al. Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria. J Heart Lung Transplant 2002; 21: 297–310.

    PubMed  Google Scholar 

  31. Burlingham WJ, Love RB, Jankowska-Gan E, Haynes LD, Xu Q, Bobadilla JL et al. IL-17-dependent cellular immunity to collagen type V predisposes to obliterative bronchiolitis in human lung transplants. J Clin Invest 2007; 117: 3498–3506.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Afzali B, Lombardi G, Lechler RI, Lord GM . The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease. Clin Exp Immunol 2007; 148: 32–46.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 2006; 441: 235–238.

    CAS  PubMed  Google Scholar 

  34. Meloni F, Vitulo P, Bianco AM, Paschetto E, Morosini M, Cascina A et al. Regulatory CD4+CD25+ T cells in the peripheral blood of lung transplant recipients: correlation with transplant outcome. Transplantation 2004; 77: 762–766.

    PubMed  Google Scholar 

  35. Nakagiri T, Inoue M, Morii E, Minami M, Sawabata N, Utsumi T et al. Local IL-17 production and a decrease in peripheral blood regulatory T cells in an animal model of bronchiolitis obliterans. Transplantation 2010; 89: 1312–1319.

    CAS  PubMed  Google Scholar 

  36. Laan M, Linden . IL-17 as a potential target for modulating airway neutrophilia. Curr Pharm Des 2002; 8: 1855–1861.

    CAS  PubMed  Google Scholar 

  37. Vanaudenaerde BM, Wuyts WA, Dupont LJ, Van Raemdonck DE, Demedts MM, Verleden GM . Interleukin-17 stimulates release of interleukin-8 by human airway smooth muscle cells in vitro: a potential role for interleukin-17 and airway smooth muscle cells in bronchiolitis obliterans syndrome. J Heart Lung Transplant 2003; 22: 1280–1283.

    PubMed  Google Scholar 

  38. Zheng L, Whitford HM, Orsida B, Levvey BJ, Bailey M, Walters EH et al. The dynamics and associations of airway neutrophilia post lung transplantation. Am J Transplant 2006; 6: 599–608.

    CAS  PubMed  Google Scholar 

  39. Verleden GM, Vanaudenaerde BM, Dupont LJ, Van Raemdonck DE . Azithromycin reduces airway neutrophilia and interleukin-8 in patients with bronchiolitis obliterans syndrome. Am J Respir Crit Care Med 2006; 174: 566–570.

    CAS  PubMed  Google Scholar 

  40. Verleden GM, Vos R, De Vleeschauwer SI, Willems-Widyastuti A, Verleden SE, Dupont LJ et al. Obliterative bronchiolitis following lung transplantation: from old to new concepts? Transpl Int 2009; 22: 771–779.

    PubMed  Google Scholar 

  41. Alousi AM, Uberti J, Ratanatharathorn V . The role of B cell depleting therapy in graft versus host disease after allogeneic hematopoietic cell transplant. Leuk Lymphoma 2010; 51: 376–389.

    PubMed  Google Scholar 

  42. Sarantopoulos S, Stevenson KE, Kim HT, Cutler CS, Bhuiya NS, Schowalter M et al. Altered B-cell homeostasis and excess BAFF in human chronic graft-versus-host disease. Blood 2009; 113: 3865–3874.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Sarantopoulos S, Stevenson KE, Kim HT, Bhuiya NS, Cutler CS, Soiffer RJ et al. High levels of B-cell activating factor in patients with active chronic graft-versus-host disease. Clin Cancer Res 2007; 13: 6107–6114.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Kuzmina Z, Weigl R, Krenn K, Petkov V, Koermoeczi U, Rottal A et al. Excess of BAFF and distortion of B-cell homeostasis in patients with newly diagnosed bronchiolitis obliterans syndrome associated with chronic graft-versus-host disease. Bone Marrow Transplantation 2011; 46 (Suppl 1): S7. Ref Type: Abstract.

    Google Scholar 

  45. Jaramillo A, Smith MA, Phelan D, Sundaresan S, Trulock E, Lynch J et al. Temporal relationship between the development of anti-HLA antibodies and the development of bronchiolitis obliterans syndrome after lung transplantation. Transplant Proc 1999; 31: 185–186.

    CAS  PubMed  Google Scholar 

  46. Maruyama T, Jaramillo A, Narayanan K, Higuchi T, Mohanakumar T . Induction of obliterative airway disease by anti-HLA class I antibodies. Am J Transplant 2005; 5: 2126–2134.

    CAS  PubMed  Google Scholar 

  47. 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: 1262–1279.

    PubMed  PubMed Central  Google Scholar 

  48. Zhu KE, Hu JY, Zhang T, Chen J, Zhong J, Lu YH . Incidence, risks, and outcome of idiopathic pneumonia syndrome early after allogeneic hematopoietic stem cell transplantation. Eur J Haematol 2008; 81: 461–466.

    PubMed  Google Scholar 

  49. Gower WA, Collaco JM, Mogayzel Jr PJ . Lung function and late pulmonary complications among survivors of hematopoietic stem cell transplantation during childhood. Paediatr Respir Rev 2010; 11: 115–122.

    PubMed  Google Scholar 

  50. Fukuda T, Hackman RC, Guthrie KA, Sandmaier BM, Boeckh M, Maris MB et al. Risks and outcomes of idiopathic pneumonia syndrome after nonmyeloablative and conventional conditioning regimens for allogeneic hematopoietic stem cell transplantation. Blood 2003; 102: 2777–2785.

    PubMed  Google Scholar 

  51. 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 Transplant 2011; 46: 1283–1295.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Wolff D, Gerbitz A, Ayuk F, Kiani A, Hildebrandt GC, Vogelsang GB et al. Consensus conference on clinical practice in chronic graft-versus-host disease (GVHD): first-line and topical treatment of chronic GVHD. Biol Blood Marrow Transplant 2010; 16: 1611–1628.

    PubMed  Google Scholar 

  53. Wolff D, Schleuning M, von HS, Bacher U, Gerbitz A, Stadler M 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: 1–17.

    PubMed  Google Scholar 

  54. Ratjen F, Rjabko O, Kremens B . High-dose corticosteroid therapy for bronchiolitis obliterans after bone marrow transplantation in children. Bone Marrow Transplant 2005; 36: 135–138.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  56. 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.

    PubMed  Google Scholar 

  57. Khalid M, Al SA, Saleemi S, Al DS, Zeitouni M, Al MA et al. Azithromycin in bronchiolitis obliterans complicating bone marrow transplantation: a preliminary study. Eur Respir J 2005; 25: 490–493.

    CAS  PubMed  Google Scholar 

  58. Lam DCL, Lam B, Wong MKY, Lu C, Au WY, Tse EWC et al. Effects of Azithromycin in bronchiolitis obliterans syndrome after hematopoietic SCT—a randomized double-blinded placebo-controlled study. Bone Marrow Transplant 2011; 46: 1551–1556.

    CAS  PubMed  Google Scholar 

  59. Busca A, Locatelli F, Marmont F, Ceretto C, Falda M . Recombinant human soluble tumor necrosis factor receptor fusion protein as treatment for steroid refractory graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. Am J Hematol 2007; 82: 45–52.

    CAS  PubMed  Google Scholar 

  60. Chiang KY, Abhyankar S, Bridges K, Godder K, Henslee-Downey JP . Recombinant human tumor necrosis factor receptor fusion protein as complementary treatment for chronic graft-versus-host disease. Transplantation 2002; 73: 665–667.

    CAS  PubMed  Google Scholar 

  61. Flowers ME, Apperley JF, van BK, 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: 2667–2674.

    CAS  PubMed  Google Scholar 

  62. Couriel DR, Hosing C, Saliba R, Shpall EJ, Anderlini P, Rhodes B et al. Extracorporeal photochemotherapy for the treatment of steroid-resistant chronic GVHD. Blood 2006; 107: 3074–3080.

    CAS  PubMed  Google Scholar 

  63. Messina C, Locatelli F, Lanino E, Uderzo C, Zacchello G, Cesaro S et al. Extracorporeal photochemotherapy for paediatric patients with graft-versus-host disease after haematopoietic stem cell transplantation. Br J Haematol 2003; 122: 118–127.

    CAS  PubMed  Google Scholar 

  64. Rubegni P, Cuccia A, Sbano P, Cevenini G, Carcagni MR, D’Ascenzo G et al. Role of extracorporeal photochemotherapy in patients with refractory chronic graft-versus-host disease. Br J Haematol 2005; 130: 271–275.

    CAS  PubMed  Google Scholar 

  65. Lucid CE, Savani BN, Engelhardt BG, Shah P, Clifton C, Greenhut SL et al. Extracorporeal photopheresis in patients with refractory bronchiolitis obliterans developing after allo-SCT. Bone Marrow Transplant 2011; 46: 426–429.

    CAS  PubMed  Google Scholar 

  66. 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: 273–277.

    CAS  PubMed  Google Scholar 

  67. 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: 1935–1942.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Jacobsohn DA, Chen AR, Zahurak M, Piantadosi S, Anders V, Bolanos-Meade J et al. Phase II study of pentostatin in patients with corticosteroid-refractory chronic graft-versus-host disease. J Clin Oncol 2007; 25: 4255–4261.

    CAS  PubMed  Google Scholar 

  69. Olivieri A, Locatelli F, Zecca M, Sanna A, Cimminiello M, Raimondi R et al. Imatinib for refractory chronic graft-versus-host disease with fibrotic features. Blood 2009; 114: 709–718.

    CAS  PubMed  Google Scholar 

  70. Stadler M, Ahlborn R, Kamal H, Diedrich H, Buchholz S, Eder M et al. Limited efficacy of imatinib in severe pulmonary chronic graft-versus-host disease. Blood 2009; 114: 3718–3719.

    CAS  PubMed  Google Scholar 

  71. Kulkarni S, Powles R, Sirohi B, Treleaven J, Saso R, Horton C et al. Thalidomide after allogeneic haematopoietic stem cell transplantation: activity in chronic but not in acute graft-versus-host disease. Bone Marrow Transplant 2003; 32: 165–170.

    CAS  PubMed  Google Scholar 

  72. Couriel D, Carpenter PA, Cutler C, Bolaños-Meade J, Treister NS, Gea-Banacloche J et al. Ancillary therapy and supportive care of chronic graft-versus-host disease: national institutes of health consensus development project on criteria for clinical trials in chronic Graft-versus-host disease: V. Ancillary Therapy and Supportive Care Working Group Report. Biol Blood Marrow Transplant 2006; 12: 375–396.

    PubMed  Google Scholar 

  73. De Jong PA, Dodd JD, Coxson HO, Storness-Bliss C, Paré PD, Mayo JR et al. Bronchiolitis obliterans following lung transplantation: early detection using computed tomographic scanning. Thorax 2006; 61: 799–804.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. American Thoracic Society. Lung function testing: selection of reference values and interpretative strategies. Am Rev Respir Dis 1992; 146 (5 Part 1): 1368–1369.

    Google Scholar 

  75. Clement A . Task force on chronic interstitial lung disease in immunocompetent children. Eur Respir J 2004; 24: 686–697.

    CAS  PubMed  Google Scholar 

  76. Desmarquest P, Tamalet A, Fauroux B, Boule M, Boccon-Gibod L, Tournier G et al. Chronic interstitial lung disease in children: response to high-dose intravenous methylprednisolone pulses. Pediatr Pulmonol 1998; 26: 332–338.

    CAS  PubMed  Google Scholar 

  77. Buchvald F, Petersen BL, Damgaard K, Deterding R, Langston C, Fan LL et al. Frequency, treatment, and functional outcome in children with hypersensitivity pneumonitis. Pediatr Pulmonol (e-pub ahead of print 26 May 2011).

    PubMed  Google Scholar 

  78. Akikusa JD, Feldman BM, Gross GJ, Silverman ED, Schneider R . Sinus bradycardia after intravenous pulse methylprednisolone. Pediatrics 2007; 119: e778–e782.

    PubMed  Google Scholar 

  79. Sullivan KM, Witherspoon RP, Storb R, Weiden P, Flournoy N, Dahlberg S 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: 546–554.

    CAS  PubMed  Google Scholar 

  80. Koc S, Leisenring W, Flowers ME, Anasetti C, Deeg HJ, Nash RA et al. Therapy for chronic graft-versus-host disease: a randomized trial comparing cyclosporine plus prednisone versus prednisone alone. Blood 2002; 100: 48–51.

    CAS  PubMed  Google Scholar 

  81. Bergeron A, Chagnon K, Feuillet S, Chevret S, Tazi A . Prospective evaluation of the efficacy of the combination of budesonide/formoterol in obstructive airway disease after allogeneic hematopoietic stem cell transplantation]. Rev Mal Respir 2009; 26: 794–800.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Fullmer JJ, Fan LL, Dishop MK, Rodgers C, Krance R . Successful treatment of bronchiolitis obliterans in a bone marrow transplant patient with tumor necrosis factor-alpha blockade. Pediatrics 2005; 116: 767–770.

    PubMed  Google Scholar 

  83. Gottlieb J, Szangolies J, Koehnlein T, Golpon H, Simon A, Welte T . Long-term azithromycin for bronchiolitis obliterans syndrome after lung transplantation. Transplantation 2008; 85: 36–41.

    CAS  PubMed  Google Scholar 

  84. Vanaudenaerde BM, Meyts I, Vos R, Geudens N, De WW, Verbeken EK et al. A dichotomy in bronchiolitis obliterans syndrome after lung transplantation revealed by azithromycin therapy. Eur Respir J 2008; 32: 832–843.

    CAS  PubMed  Google Scholar 

  85. 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 SCT: a case series of eight patients. Bone Marrow Transplant 2011; 46: 1369–1373.

    CAS  PubMed  Google Scholar 

  86. Kanold J, Merlin E, Halle P, Paillard C, Marabelle A, Rapatel C et al. Photopheresis in pediatric graft-versus-host disease after allogeneic marrow transplantation: clinical practice guidelines based on field experience and review of the literature. Transfusion 2007; 47: 2276–2289.

    PubMed  Google Scholar 

  87. Ilhan O, Arat M, Arslan O, Ayyildiz E, Sanli H, Beksac M et al. Extracorporeal photoimmunotherapy for the treatment of steroid refractory progressive chronic graft-versus-host disease. Transfus Apher Sci 2004; 30: 185–187.

    PubMed  Google Scholar 

  88. Garban F, Drillat P, Makowski C, Jacob MC, Richard MJ, Favrot M et al. Extracorporeal chemophototherapy for the treatment of graft-versus-host disease: hematologic consequences of short-term, intensive courses. Haematologica 2005; 90: 1096–1101.

    PubMed  Google Scholar 

  89. Foss FM, DiVenuti GM, Chin K, Sprague K, Grodman H, Klein A et al. Prospective study of extracorporeal photopheresis in steroid-refractory or steroid-resistant extensive chronic graft-versus-host disease: analysis of response and survival incorporating prognostic factors. Bone Marrow Transplant 2005; 35: 1187–1193.

    CAS  PubMed  Google Scholar 

  90. Berger M, Pessolano R, Albiani R, Asaftei S, Barat V, Carraro F et al. Extracorporeal photopheresis for steroid resistant graft versus host disease in pediatric patients: a pilot single institution report. J Pediatr Hematol Oncol 2007; 29: 678–687.

    PubMed  Google Scholar 

  91. Bisaccia E, Palangio M, Gonzalez J, Adler KR, Scarborough R, Goldberg SL et al. Treatment of extensive chronic graft-versus-host disease with extracorporeal photochemotherapy. J Clin Apher 2006; 21: 181–187.

    PubMed  Google Scholar 

  92. O’Hagan AR, Stillwell PC, Arroliga A, Koo A . Photopheresis in the treatment of refractory bronchiolitis obliterans complicating lung transplantation. Chest 1999; 115: 1459–1462.

    PubMed  Google Scholar 

  93. Benden C, Speich R, Hofbauer GF, Irani S, Eich-Wanger C, Russi EW et al. Extracorporeal photopheresis after lung transplantation: a 10-year single-center experience. Transplantation 2008; 86: 1625–1627.

    PubMed  Google Scholar 

  94. Morrell MR, Despotis GJ, Lublin DM, Patterson GA, Trulock EP, Hachem RR . The efficacy of photopheresis for bronchiolitis obliterans syndrome after lung transplantation. J Heart Lung Transplant 2010; 29: 424–431.

    PubMed  Google Scholar 

  95. Kharfan-Dabaja MA, Mhaskar AR, Djulbegovic B, Cutler C, Mohty M, Kumar A . 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: 1005–1013.

    CAS  PubMed  Google Scholar 

  96. Teshima T, Nagafuji K, Henzan H, Miyamura K, Takase K, Hidaka M et al. Rituximab for the treatment of corticosteroid-refractory chronic graft-versus-host disease. Int J Hematol 2009; 90: 253–260.

    PubMed  Google Scholar 

  97. Cutler C, Miklos D, Kim HT, Treister N, Woo SB, Bienfang D et al. Rituximab for steroid-refractory chronic graft-versus-host disease. Blood 2006; 108: 756–762.

    CAS  PubMed  PubMed Central  Google Scholar 

  98. von BM, Oelschlagel U, Radke J, Stewart M, Ehninger G, Bornhauser M et al. Treatment of chronic steroid-refractory graft-versus-host disease with low-dose rituximab. Transplantation 2008; 86: 875–879.

    Google Scholar 

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Acknowledgements

This work was supported by grants from the Danish Children's Cancer Association and the Research Council at the National University Hospital Rigshospitalet.

Author information

Authors and Affiliations

  1. Paediatric Clinic, National University Hospital Rigshospitalet, Copenhagen, Denmark

    H H Uhlving, F Buchvald, C J Heilmann, K G Nielsen & K G Müller

  2. Department of Rheumatology, Institute of Inflammation Research, National University Hospital Rigshospitalet, Copenhagen, Denmark

    H H Uhlving & K G Müller

  3. Paediatric Pulmonary Service, National University Hospital Rigshospitalet, Copenhagen, Denmark

    F Buchvald & K G Nielsen

  4. Department of Radiology, National University Hospital Rigshospitalet, Copenhagen, Denmark

    M Gormsen

Authors
  1. H H Uhlving
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  2. F Buchvald
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  3. C J Heilmann
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  4. K G Nielsen
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  5. M Gormsen
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  6. K G Müller
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Correspondence to H H Uhlving.

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Uhlving, H., Buchvald, F., Heilmann, C. et al. Bronchiolitis obliterans after allo-SCT: clinical criteria and treatment options. Bone Marrow Transplant 47, 1020–1029 (2012). https://doi.org/10.1038/bmt.2011.161

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  • DOI: https://doi.org/10.1038/bmt.2011.161

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