Journal of Clinical Apheresis 00:00–00 (2015)
Effect of Extracorporeal Photopheresis on Lung Function Decline for Severe Bronchiolitis Obliterans Syndrome Following Allogeneic Stem Cell Transplantation Kyle R. Brownback,1* Steven Q. Simpson,1 Lucas R. Pitts,1 Deepika Polineni,1 Joseph P. McGuirk,2 Siddhartha Ganguly,2 Omar S. Aljitawi,2 Tara L. Lin,2 Anurag Singh,2 and Sunil Abhyankar2 1
Division of Pulmonary and Critical Care Medicine, University of Kansas Medical Center, Kansas City, Kansas 2 Division of Hematology and Oncology, University of Kansas Medical Center, Kansas City, Kansas Extracorporeal photopheresis (ECP) is a commonly used treatment for severe graft-versus-host-disease (GVHD). We sought to evaluate the effects of ECP over a prolonged period on forced expiratory volume in 1 s (FEV1) in patients with pulmonary GVHD. We identified eight patients who developed new airflow obstruction following allogeneic stem cell transplantation and a substantial decline in FEV1 despite receiving corticosteroids and standard therapy for pulmonary GVHD. Those eight patients were treated with ECP for a period of 1 year, with a primary endpoint of FEV1 change during this treatment period. Over the first 3 months of ECP, there was no further decline in FEV1 in seven of the eight patients. However, over the 1 year period, only two of the eight patients had stability in FEV1. The rate of FEV1 decline was substantially less once ECP was initiated, though the median FEV1 continued to decline over 1 year of therapy. All patients survived through the first year of ECP therapy. There was a significant decrease in the median dose of prednisone per patient throughout the 12 months of ECP treatment. ECP shows promise in slowing rate of decline of FEV1 in pulmonary GVHD, though C 2015 Wiley Periodicals, Inc. the effects may not be long lived. J. Clin. Apheresis 00:000–000, 2015. V Key words: bronchiolitis obliterans syndrome; extracorporeal photopheresis; graft-versus-host-disease; pulmonary function testing; stem cell transplantation
INTRODUCTION
Chronic graft-versus-host-disease (GVHD) is a major barrier to long-term survival following allogeneic hematopoietic stem cell transplantation (HSCT). Chronic GVHD is defined as the emergence of specific signs or symptoms of GVHD between 100 days and 3 years following allogeneic HSCT, with features similar to autoimmune disorders, and often follows acute GVHD [1]. Chronic GVHD may be widespread or confined to a single organ system, and often causes significant debilitation and potentially death. The estimated incidence of chronic GVHD is between 6 and 80%, with that variability occurring due to differences in diagnostic criteria and patient risk factors [2–5]. First line treatment of chronic GVHD typically involves immunosuppression with topical or systemic corticosteroids, with alternative agents reserved for refractory cases [1]. Extracorporeal photopheresis (ECP) is an immunomodulatory therapy in which the blood is divided into separate components, upon which the isolated buffy coat is exposed to ultraviolet light and then returned to the patient [6]. ECP has been employed in the treatment of many conditions, including cutaneous T-cell C 2015 Wiley Periodicals, Inc. V
lymphoma, Crohn’s disease, systemic sclerosis, lung transplant rejection, and GVHD. In chronic GVHD, ECP has many advantages over traditional treatments such as corticosteroids, specifically in the lack of significant associated side effects. Chronic GVHD involving the lungs can present in different ways, including bronchiolitis obliterans syndrome (BOS), idiopathic pneumonia syndrome, and organizing pneumonia [7]. BOS, which is manifested as circumferential fibrosis of terminal airways, is the most common form of pulmonary GVHD [8]. BOS is diagnosed either by lung biopsy, or based on new or worsening fixed airflow obstruction on pulmonary function testing (PFT) following allogeneic HSCT with evidence of air trapping or bronchiectasis on highresolution chest CT. The clinical course is *Correspondence to: Kyle R. Brownback, Division of Pulmonary and Critical Care Medicine, University of Kansas Medical Center, 3901 Rainbow Blvd., Mail Stop 3007, Kansas City, KS 66160, USA. E-mail: [email protected]. Received 11 February 2015; Accepted 29 April 2015 Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jca.21404
2
Brownback et al.
unpredictable, varying from a slow decline in lung function over several years to a precipitous drop leading to respiratory failure within a few months [1]. BOS is also the prevailing manifestation of chronic lung allograft rejection, and is the leading cause of death in lung transplant recipients after the second posttransplant year [9]. Therapy for BOS associated with chronic GVHD is diverse, employing agents such as systemic and topical corticosteroids, mTOR inhibitors, azithromycin, montelukast, imatinib, and various combinations of these agents [10]. ECP can improve GVHD scores [11], and stabilizes lung function decline in BOS following lung transplantation [12,13]. We hypothesized that ECP would stabilize or improve the pulmonary manifestations of GVHD in HSCT patients and performed this observational study to determine the effects of ECP on lung function in HSCT-induced BOS over a 1-year period.
MATERIALS AND METHODS
Patients were identified from the apheresis records of the University of Kansas Medical Center. All patients had a history of allogeneic HSCT from peripheral blood stem cell source and were receiving ECP for treatment of chronic, extensive GVHD that was graded as severe by NIH criteria. From those records, we identified patients with severe BOS as a manifestation of pulmonary GVHD. BOS was defined by PFTs showing a forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio of less than 0.7, along with a FEV1 of 500,000
Photopheresis for Severe Pulmonary GVHD
ECP treatments have been performed worldwide, and the reported incidence of side effects is very low at less than 0.003% [29]. BOS also occurs in the lung transplant population as the predominant manifestation of chronic allograft rejection, and experience with ECP in this population is much larger than in the post-HSCT patient subset. One retrospective study of 65 patients with declining lung function despite receiving azithromycin showed that 53.8% either had stability or improvement in FEV1 over a median of 538 days [30]. Another study of 51 lung transplant recipients showed that 61% of patients had stability of FEV1 after 6 months of ECP therapy, although a substantial portion of patients had ongoing decline in lung function in subsequent months [12]. One earlier study revealed a decrease in the slope of decline of FEV1 upon ECP initiation in 60 lung allograft recipients with BOS [13]. These studies demonstrate that while many patients have improvement in lung function with ECP, a substantial proportion of patients fail to respond to this treatment. Identifying potential responders may be more important than implementing ECP across the board in patients with BOS; as of yet, no biomarkers of progression have been identified. Our study has some limitations. The small number of patients, with differing background medical histories, infectious pathogens and immunosuppressive regimens makes it difficult to judge the ultimate effect of ECP on FEV1. The ongoing decline in FEV1 once ECP was initiated may be due to reduced frequency of ECP treatments after the first 3 months of therapy, and future studies should focus on frequency of treatment with ECP on GVHD scoring. Additionally, the natural history of BOS following GVHD is highly variable, and whether ECP is changing the progression of the disease will be difficult to judge in the absence of a well-designed randomized, controlled clinical trial. Our recognition that median daily dose of prednisone decreased during the study period may serve as a surrogate for overall improvement in GVHD severity.
CONCLUSION
Institution of ECP in patients with severe BOS following HSCT is associated with a slower rate of decline in FEV1 than before initiation of the therapy. ECP appeared to facilitate prescription of a lower dose of prednisone to all eight patients that persisted throughout the first year of ECP treatment. While the majority of patients had stability or improvement in FEV1 over the first 3 months of ECP therapy, only 25% avoided a further decline of FEV1 over a 1 year treatment period with ECP. ECP holds promise as a therapeutic modality for patients with BOS following
5
HSCT; however, it is difficult to determine which patients may benefit the most from therapy. REFERENCES 1. Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National institutes of health consensus development project on criteria for clinical trials in chronic graftversus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005;11:945–956. 2. Atkinson K, Horowitz MM, Gale RP, van Bekkum DW, Gluckman E, Good RA, Jacobsen N, Kolb HJ, Rimm AA, Ringden O. Risk factors for chronic graft-versus-host disease after HLA-identical sibling bone marrow transplantation. Blood 1990;75:2459–2464. 3. Carlens S, Ringden O, Remberger M, Lonnqvist B, Hagglund H, Klaesson S, Mattsson J, Svahn Bm, Winiarski J, Ljungman P, Aschan J. Risk factors for chronic graft-versus-host disease after bone marrow transplantation: A retrospective single centre analysis. Bone Marrow Transplant 1998;22:755–761. 4. Rocha V, Wagner JE, Jr., Sobocinski KA, Klein JP, Zhang MJ, Horowitz MM, Horowitz MM, Gluckman E. Graft-versus-host disease in children who have received a cord-blood or bone marrow transplant from an HLA-identical sibling. Eurocord and international bone marrow transplant registry working committee on alternative donor and stem cell sources. N Engl J Med 2000;342:1846–1854. 5. Sullivan KM, Agura E, Anasetti C, Appelbaum F, Badger C, Bearman S, Erickson K, Flowers M, Hansen J, Loughran T. Chronic graft-versus-host disease and other late complications of bone marrow transplantation. Semin Hematol 1991;28:250– 259. 6. Sanford KW, Balogun RA. Extracorporeal photopheresis: Clinical use so far. J Clin Apheresis 2012;27:126–131. 7. Yanik G, Kitko C. Management of noninfectious lung injury following hematopoietic cell transplantation. Curr Opin Oncol 2013;25:187–194. 8. Williams KM, Chien JW, Gladwin MT, Pavletic SZ. Bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation. JAMA 2009;302:306–314. 9. Christie JD, Edwards LB, Aurora P, Dobbels F, Kirk R, Rahmel AO, Taylor Do, Kucheryavaya AY, Hertz MI. Registry of the international society for heart and lung transplantation: twentyfifth official adult lung and heart/lung transplantation report– 2008. J Heart Lung Transplant 2008;27:957–969. 10. Hildebrandt GC, Fazekas T, Lawitschka A, Bertz H, Greinix H, Halter J, Pavletic SZ, Holler E, Wolff D. 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. 11. Couriel D, Hosing C, Saliba R, Shpall EJ, Andelini P, Popat U, Donato M, Champlin R. Extracorporeal photopheresis for acute and chronic graft-versus-host disease: Does it work? Biol Blood Marrow Transplant 2006;12(1 Suppl 2):37–40. 12. Jaksch P, Scheed A, Keplinger M, Ernst MB, Dani T, Just U, Nahavandi H, Klepetko W, Knobler R. A prospective interventional study on the use of extracorporeal photopheresis in patients with bronchiolitis obliterans syndrome after lung transplantation. J Heart Lung Transplant 2012;31:950–957. 13. Morrell MR, Despotis GJ, Lublin DM, Patterson GA, Trulock EP, Hachem RR. The efficacy of photopheresis for bronchiolitis Journal of Clinical Apheresis DOI 10.1002/jca
6
14.
15.
16.
17.
18.
19.
20.
21.
22.
Brownback et al. obliterans syndrome after lung transplantation. J Heart Lung Transplant 2010;29:424–431. Di Biaso I, Di Maio L, Bugarin C, Gaipa G, Dander E, Balduzzi A, et al. Regulatory T cells and extracorporeal photochemotherapy: Correlation with clinical response and decreased frequency of proinflammatory T cells. Transplantation 2009;87: 1422–1425. Lucid CE, Savani BN, Engelhardt BG, Shah P, Clifton C, Greenhut SL, Vaughan LA, Kassim A, Schuening F, Jagasi M. Extracorporeal photopheresis in patients with refractory bronchiolitis obliterans developing after allo-SCT. Bone Marrow Transplant 2011;46:426–429. Chien JW, Martin PJ, Gooley TA, Flowers ME, Heckbert SR, Nichols WG, Clark JG. Airflow obstruction after myeloablative allogeneic hematopoietic stem cell transplantation. Am J Respir Crit Care Med 2003;168:208–214. 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. Santo Tomas LH, Loberiza FR, Jr., Klein JP, Layde PM, Lipchik RJ, Rizzo JD, Bredeson CN, Horowitz MM. Risk factors for bronchiolitis obliterans in allogeneic hematopoietic stem-cell transplantation for leukemia. Chest 2005;128:153–161. 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 Transplant 2007;13:749–759. Afessa B, Litzow MR, Tefferi A. Bronchiolitis obliterans and other late onset non-infectious pulmonary complications in hematopoietic stem cell transplantation. Bone Marrow Transplant 2001;28:425–434. 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. 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.
Journal of Clinical Apheresis DOI 10.1002/jca
23. Bashoura L, Gupta S, Jain A, Couriel DR, Komanduri KV, Eapen GA, Safdar A, Broglio KR, Adachi R, Dickey BF. Inhaled corticosteroids stabilize constrictive bronchiolitis after hematopoietic stem cell transplantation. Bone Marrow Transplant 2008;41:63–67. 24. Khalid M, Al Saghir A, Saleemi S, Al Dammas S, Zeitouni M, Al Mobeireek A, Chaudhry N, Sahovic E. Azithromycin in bronchiolitis obliterans complicating bone marrow transplantation: A preliminary study. Eur Respir J 2005;25:490–493. 25. Or R, Gesundheit B, Resnick I, Bitan M, Avraham A, Avgil M, Sacks Z, Shapira MY. Sparing effect by montelukast treatment for chronic graft versus host disease: A pilot study. Transplantation 2007;83:577–581. 26. Norman BC, Jacobsohn DA, Williams KM, Au BK, Au MA, Lee SJ, Moravec CK, Chien JW. 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. 27. Pierelli L, Perseghin P, Marchetti M, Messina C, Perotti C, Mazzoni A, Bacigalupo A, Locatelli F, Carlier P, Bosi A. Extracorporeal photopheresis for the treatment of acute and chronic graft-versus-host disease in adults and children: Best practice recommendations from an Italian society of hemapheresis and cell manipulation (SIdEM) and Italian group for bone marrow transplantation (GITMO) consensus process. Transfusion 2013;53:2340–2352. 28. Biagi E, Di Biaso I, Leoni V, Gaipa G, Rossi V, Bugarin C, Renoldi G, Parma M, Balduzzi A, Perseghin P, Biondi A. Extracorporeal photochemotherapy is accompanied by increasing levels of circulating cd41cd251GITR1foxp31 CD62L1 functional regulatory T-cells in patients with graft-versus-host disease. Transplantation 2007;84:31–39. 29. Klassen J. The role of photopheresis in the treatment of graftversus-host disease. Curr Oncol 2010;17:55–58. 30. Greer M, Dierich M, De Wall C, Suhling H, Rademacher J, Welte T, Haverich A, Warnecke G, Ivanyi P, Buchholz S. Gottlieb J, Fuehner T. Phenotyping established chronic lung allograft dysfunction predicts extracorporeal photopheresis response in lung transplant patients. Am J Transplant 2013;13:911–918.
Effect of Extracorporeal Photopheresis on Lung Function Decline for Severe Bronchiolitis Obliterans Syndrome Following Allogeneic Stem Cell Transplantation Kyle R. Brownback,1* Steven Q. Simpson,1 Lucas R. Pitts,1 Deepika Polineni,1 Joseph P. McGuirk,2 Siddhartha Ganguly,2 Omar S. Aljitawi,2 Tara L. Lin,2 Anurag Singh,2 and Sunil Abhyankar2 1
Division of Pulmonary and Critical Care Medicine, University of Kansas Medical Center, Kansas City, Kansas 2 Division of Hematology and Oncology, University of Kansas Medical Center, Kansas City, Kansas Extracorporeal photopheresis (ECP) is a commonly used treatment for severe graft-versus-host-disease (GVHD). We sought to evaluate the effects of ECP over a prolonged period on forced expiratory volume in 1 s (FEV1) in patients with pulmonary GVHD. We identified eight patients who developed new airflow obstruction following allogeneic stem cell transplantation and a substantial decline in FEV1 despite receiving corticosteroids and standard therapy for pulmonary GVHD. Those eight patients were treated with ECP for a period of 1 year, with a primary endpoint of FEV1 change during this treatment period. Over the first 3 months of ECP, there was no further decline in FEV1 in seven of the eight patients. However, over the 1 year period, only two of the eight patients had stability in FEV1. The rate of FEV1 decline was substantially less once ECP was initiated, though the median FEV1 continued to decline over 1 year of therapy. All patients survived through the first year of ECP therapy. There was a significant decrease in the median dose of prednisone per patient throughout the 12 months of ECP treatment. ECP shows promise in slowing rate of decline of FEV1 in pulmonary GVHD, though C 2015 Wiley Periodicals, Inc. the effects may not be long lived. J. Clin. Apheresis 00:000–000, 2015. V Key words: bronchiolitis obliterans syndrome; extracorporeal photopheresis; graft-versus-host-disease; pulmonary function testing; stem cell transplantation
INTRODUCTION
Chronic graft-versus-host-disease (GVHD) is a major barrier to long-term survival following allogeneic hematopoietic stem cell transplantation (HSCT). Chronic GVHD is defined as the emergence of specific signs or symptoms of GVHD between 100 days and 3 years following allogeneic HSCT, with features similar to autoimmune disorders, and often follows acute GVHD [1]. Chronic GVHD may be widespread or confined to a single organ system, and often causes significant debilitation and potentially death. The estimated incidence of chronic GVHD is between 6 and 80%, with that variability occurring due to differences in diagnostic criteria and patient risk factors [2–5]. First line treatment of chronic GVHD typically involves immunosuppression with topical or systemic corticosteroids, with alternative agents reserved for refractory cases [1]. Extracorporeal photopheresis (ECP) is an immunomodulatory therapy in which the blood is divided into separate components, upon which the isolated buffy coat is exposed to ultraviolet light and then returned to the patient [6]. ECP has been employed in the treatment of many conditions, including cutaneous T-cell C 2015 Wiley Periodicals, Inc. V
lymphoma, Crohn’s disease, systemic sclerosis, lung transplant rejection, and GVHD. In chronic GVHD, ECP has many advantages over traditional treatments such as corticosteroids, specifically in the lack of significant associated side effects. Chronic GVHD involving the lungs can present in different ways, including bronchiolitis obliterans syndrome (BOS), idiopathic pneumonia syndrome, and organizing pneumonia [7]. BOS, which is manifested as circumferential fibrosis of terminal airways, is the most common form of pulmonary GVHD [8]. BOS is diagnosed either by lung biopsy, or based on new or worsening fixed airflow obstruction on pulmonary function testing (PFT) following allogeneic HSCT with evidence of air trapping or bronchiectasis on highresolution chest CT. The clinical course is *Correspondence to: Kyle R. Brownback, Division of Pulmonary and Critical Care Medicine, University of Kansas Medical Center, 3901 Rainbow Blvd., Mail Stop 3007, Kansas City, KS 66160, USA. E-mail: [email protected]. Received 11 February 2015; Accepted 29 April 2015 Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jca.21404
2
Brownback et al.
unpredictable, varying from a slow decline in lung function over several years to a precipitous drop leading to respiratory failure within a few months [1]. BOS is also the prevailing manifestation of chronic lung allograft rejection, and is the leading cause of death in lung transplant recipients after the second posttransplant year [9]. Therapy for BOS associated with chronic GVHD is diverse, employing agents such as systemic and topical corticosteroids, mTOR inhibitors, azithromycin, montelukast, imatinib, and various combinations of these agents [10]. ECP can improve GVHD scores [11], and stabilizes lung function decline in BOS following lung transplantation [12,13]. We hypothesized that ECP would stabilize or improve the pulmonary manifestations of GVHD in HSCT patients and performed this observational study to determine the effects of ECP on lung function in HSCT-induced BOS over a 1-year period.
MATERIALS AND METHODS
Patients were identified from the apheresis records of the University of Kansas Medical Center. All patients had a history of allogeneic HSCT from peripheral blood stem cell source and were receiving ECP for treatment of chronic, extensive GVHD that was graded as severe by NIH criteria. From those records, we identified patients with severe BOS as a manifestation of pulmonary GVHD. BOS was defined by PFTs showing a forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio of less than 0.7, along with a FEV1 of 500,000
Photopheresis for Severe Pulmonary GVHD
ECP treatments have been performed worldwide, and the reported incidence of side effects is very low at less than 0.003% [29]. BOS also occurs in the lung transplant population as the predominant manifestation of chronic allograft rejection, and experience with ECP in this population is much larger than in the post-HSCT patient subset. One retrospective study of 65 patients with declining lung function despite receiving azithromycin showed that 53.8% either had stability or improvement in FEV1 over a median of 538 days [30]. Another study of 51 lung transplant recipients showed that 61% of patients had stability of FEV1 after 6 months of ECP therapy, although a substantial portion of patients had ongoing decline in lung function in subsequent months [12]. One earlier study revealed a decrease in the slope of decline of FEV1 upon ECP initiation in 60 lung allograft recipients with BOS [13]. These studies demonstrate that while many patients have improvement in lung function with ECP, a substantial proportion of patients fail to respond to this treatment. Identifying potential responders may be more important than implementing ECP across the board in patients with BOS; as of yet, no biomarkers of progression have been identified. Our study has some limitations. The small number of patients, with differing background medical histories, infectious pathogens and immunosuppressive regimens makes it difficult to judge the ultimate effect of ECP on FEV1. The ongoing decline in FEV1 once ECP was initiated may be due to reduced frequency of ECP treatments after the first 3 months of therapy, and future studies should focus on frequency of treatment with ECP on GVHD scoring. Additionally, the natural history of BOS following GVHD is highly variable, and whether ECP is changing the progression of the disease will be difficult to judge in the absence of a well-designed randomized, controlled clinical trial. Our recognition that median daily dose of prednisone decreased during the study period may serve as a surrogate for overall improvement in GVHD severity.
CONCLUSION
Institution of ECP in patients with severe BOS following HSCT is associated with a slower rate of decline in FEV1 than before initiation of the therapy. ECP appeared to facilitate prescription of a lower dose of prednisone to all eight patients that persisted throughout the first year of ECP treatment. While the majority of patients had stability or improvement in FEV1 over the first 3 months of ECP therapy, only 25% avoided a further decline of FEV1 over a 1 year treatment period with ECP. ECP holds promise as a therapeutic modality for patients with BOS following
5
HSCT; however, it is difficult to determine which patients may benefit the most from therapy. REFERENCES 1. Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National institutes of health consensus development project on criteria for clinical trials in chronic graftversus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005;11:945–956. 2. Atkinson K, Horowitz MM, Gale RP, van Bekkum DW, Gluckman E, Good RA, Jacobsen N, Kolb HJ, Rimm AA, Ringden O. Risk factors for chronic graft-versus-host disease after HLA-identical sibling bone marrow transplantation. Blood 1990;75:2459–2464. 3. Carlens S, Ringden O, Remberger M, Lonnqvist B, Hagglund H, Klaesson S, Mattsson J, Svahn Bm, Winiarski J, Ljungman P, Aschan J. Risk factors for chronic graft-versus-host disease after bone marrow transplantation: A retrospective single centre analysis. Bone Marrow Transplant 1998;22:755–761. 4. Rocha V, Wagner JE, Jr., Sobocinski KA, Klein JP, Zhang MJ, Horowitz MM, Horowitz MM, Gluckman E. Graft-versus-host disease in children who have received a cord-blood or bone marrow transplant from an HLA-identical sibling. Eurocord and international bone marrow transplant registry working committee on alternative donor and stem cell sources. N Engl J Med 2000;342:1846–1854. 5. Sullivan KM, Agura E, Anasetti C, Appelbaum F, Badger C, Bearman S, Erickson K, Flowers M, Hansen J, Loughran T. Chronic graft-versus-host disease and other late complications of bone marrow transplantation. Semin Hematol 1991;28:250– 259. 6. Sanford KW, Balogun RA. Extracorporeal photopheresis: Clinical use so far. J Clin Apheresis 2012;27:126–131. 7. Yanik G, Kitko C. Management of noninfectious lung injury following hematopoietic cell transplantation. Curr Opin Oncol 2013;25:187–194. 8. Williams KM, Chien JW, Gladwin MT, Pavletic SZ. Bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation. JAMA 2009;302:306–314. 9. Christie JD, Edwards LB, Aurora P, Dobbels F, Kirk R, Rahmel AO, Taylor Do, Kucheryavaya AY, Hertz MI. Registry of the international society for heart and lung transplantation: twentyfifth official adult lung and heart/lung transplantation report– 2008. J Heart Lung Transplant 2008;27:957–969. 10. Hildebrandt GC, Fazekas T, Lawitschka A, Bertz H, Greinix H, Halter J, Pavletic SZ, Holler E, Wolff D. 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. 11. Couriel D, Hosing C, Saliba R, Shpall EJ, Andelini P, Popat U, Donato M, Champlin R. Extracorporeal photopheresis for acute and chronic graft-versus-host disease: Does it work? Biol Blood Marrow Transplant 2006;12(1 Suppl 2):37–40. 12. Jaksch P, Scheed A, Keplinger M, Ernst MB, Dani T, Just U, Nahavandi H, Klepetko W, Knobler R. A prospective interventional study on the use of extracorporeal photopheresis in patients with bronchiolitis obliterans syndrome after lung transplantation. J Heart Lung Transplant 2012;31:950–957. 13. Morrell MR, Despotis GJ, Lublin DM, Patterson GA, Trulock EP, Hachem RR. The efficacy of photopheresis for bronchiolitis Journal of Clinical Apheresis DOI 10.1002/jca
6
14.
15.
16.
17.
18.
19.
20.
21.
22.
Brownback et al. obliterans syndrome after lung transplantation. J Heart Lung Transplant 2010;29:424–431. Di Biaso I, Di Maio L, Bugarin C, Gaipa G, Dander E, Balduzzi A, et al. Regulatory T cells and extracorporeal photochemotherapy: Correlation with clinical response and decreased frequency of proinflammatory T cells. Transplantation 2009;87: 1422–1425. Lucid CE, Savani BN, Engelhardt BG, Shah P, Clifton C, Greenhut SL, Vaughan LA, Kassim A, Schuening F, Jagasi M. Extracorporeal photopheresis in patients with refractory bronchiolitis obliterans developing after allo-SCT. Bone Marrow Transplant 2011;46:426–429. Chien JW, Martin PJ, Gooley TA, Flowers ME, Heckbert SR, Nichols WG, Clark JG. Airflow obstruction after myeloablative allogeneic hematopoietic stem cell transplantation. Am J Respir Crit Care Med 2003;168:208–214. 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. Santo Tomas LH, Loberiza FR, Jr., Klein JP, Layde PM, Lipchik RJ, Rizzo JD, Bredeson CN, Horowitz MM. Risk factors for bronchiolitis obliterans in allogeneic hematopoietic stem-cell transplantation for leukemia. Chest 2005;128:153–161. 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 Transplant 2007;13:749–759. Afessa B, Litzow MR, Tefferi A. Bronchiolitis obliterans and other late onset non-infectious pulmonary complications in hematopoietic stem cell transplantation. Bone Marrow Transplant 2001;28:425–434. 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. 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.
Journal of Clinical Apheresis DOI 10.1002/jca
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