Extracorporeal photopheresis to attenuate decline in lung function due to refractory obstructive allograft dysfunction

EPI Study Group; Chadi A Hage; Julia Klesney-Tait; Keith Wille; Selim Arcasoy; Gordon Yung; Marshall Hertz; Kevin M Chan; Matt Morrell; Hilary Goldberg; Suresh Vedantham; Mary Clare Derfler; Paul Commean; Keith Berman; Ed Spitznagel; Jeff Atkinson; George Despotis

doi:10.1111/tme.12779

Extracorporeal photopheresis to attenuate decline in lung function due to refractory obstructive allograft dysfunction

Transfus Med. 2021 Aug;31(4):292-302. doi: 10.1111/tme.12779. Epub 2021 May 5.

Authors

EPI Study Group; Chadi A Hage¹, Julia Klesney-Tait², Keith Wille³, Selim Arcasoy⁴, Gordon Yung⁵, Marshall Hertz⁶, Kevin M Chan⁷, Matt Morrell⁸, Hilary Goldberg⁹, Suresh Vedantham¹⁰, Mary Clare Derfler¹⁰, Paul Commean¹¹, Keith Berman¹², Ed Spitznagel¹³, Jeff Atkinson¹⁴, George Despotis¹⁵

Affiliations

¹ Department of Medicine, Division of Pulmonology, Indiana University, Bloomington, Indiana, USA.
² Department of Medicine, Division of Pulmonology, University of Iowa, Iowa City, Iowa, USA.
³ Department of Medicine, Division of Pulmonology, University of Alabama, Tuscaloosa, Alabama, USA.
⁴ Department of Medicine, Division of Pulmonology, Columbia University of Alabama, Orange Beach, Alabama, USA.
⁵ Division of Pulmonary, Critical Care, and Sleep Medicine, University of California San Diego, La Jolla, California, USA.
⁶ Department of Medicine, Division of Pulmonology, University of Minnesota, Minneapolis, Minnesota, USA.
⁷ Department of Medicine, Division of Pulmonology, University of Michigan, Ann Arbor, Michigan, USA.
⁸ Department of Medicine, Division of Pulmonology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
⁹ Harvard Medical School, Department of Medicine, Division of Pulmonology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
¹⁰ Clinical Coordinating Center, Washington University School of Medicine, Mallinckrodt Institute of Radiology, St. Louis, Missouri, USA.
¹¹ Data Coordinating Center, Washington University School of Medicine, Mallinckrodt Institute of Radiology, St. Louis, Missouri, USA.
¹² Health Research Associates, Mountlake Terrace, Washington, USA.
¹³ Department of Mathematics, Washington University, St. Louis, Missouri, USA.
¹⁴ Department of Internal Medicine, Division of Pulmonary Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
¹⁵ Department of Pathology & Immunology, Division of Laboratory & Genomic Medicine, Department of Anesthesiology, Division of Cardiothoracic Anesthesiology, Washington University School of Medicine, St. Louis, Missouri, USA.

Abstract

Background: This study was designed to prospectively evaluate the efficacy of extracorporeal photopheresis (ECP) to attenuate the rate of decline of FEV₁ in lung transplant recipients with refractory bronchiolitis obliterans. Due to an observed higher than expected early mortality, a preliminary analysis was performed.

Study design and methods: Subjects from 10 lung transplant centres were assigned to ECP treatment or to observation based on spirometric criteria, with potential crossover for those under observation. The primary endpoint of this study was to assess response to ECP (i.e., greater than a 50% decrease in the rate of FEV₁ decline) before and 6 months after initiation of ECP. Mortality was also evaluated 6 and 12 months after enrolment as a secondary endpoint.

Results: Of 44 enrolled subjects, 31 were assigned to ECP treatment while 13 were initially assigned to observation on a non-random basis using specific spirometric inclusion criteria (seven of the observation patients subsequently crossed over to receive ECP). Of evaluable patients, 95% of patients initially assigned to treatment responded to ECP with rates of FEV₁ decline that were reduced by 93% in evaluable ECP-treated patients. Mortality rates (percentages) at 6 and 12 months after enrolment was 32% and 41%, respectively. The most common (92%) primary cause of death was respiratory or graft failure. Significantly (p = 0.002) higher rates of FEV₁ decline were observed in the non-survivors (-212 ± 177 ml/month) when compared to the survivors (-95 ± 117 ml/month) 12 months after enrolment. In addition, 18 patients with bronchiolitis obliterans syndrome (BOS) diagnosis within 6 months of enrolment had lost 38% of their baseline lung function at BOS diagnosis and 50% of their lung function at enrolment.

Conclusions: These analyses suggest that earlier detection and treatment of BOS should be considered to appreciate improved outcomes with ECP.

Keywords: bronchiolitis obliterans syndrome; extracorporeal photopheresis; forced expiratory volume in 1 s; lung transplantation.

MeSH terms

Allografts
Bronchiolitis Obliterans* / therapy
Humans
Lung
Lung Transplantation*
Photopheresis*

Abstract

MeSH terms

Grants and funding