Extracorporeal Photopheresis in CLAD: A 15-Year Single Centre Experience

Abstract

<h3>Purpose</h3> Use of extracorporeal photopheresis (ECP) in chronic lung allograft dysfunction (CLAD) extends over 25 years. Various single centre reports suggest some benefit, but unequivocal data is lacking. Methodology and changes in CLAD definitions have hindered comparisons, and uncertainty remains about ECP efficacy in current CLAD phenotypes. This study summaries our experience of ECP in CLAD, assessing outcomes and determining treatment duration. <h3>Methods</h3> A retrospective review of all patients receiving ECP for CLAD was performed. Data from legacy patients was reanalysed according to current definitions. Patients were treated with 2-cycles fortnightly, or occasionally 1-cycle weekly for 6 months depending on resources. Primary outcomes were nature of ECP response: stabilized, partial response or non-response and graft survival. Secondary endpoints include time to ECP response and the effect of CLAD phenotype shift during ECP, particularly regarding timing and development of restrictive spirometry. <h3>Results</h3> In total 369 patients commenced ECP for CLAD. Median follow-up was 27 [IQR 8.6-70.6] months. Graft stabilization was achieved in 140/369 (38%) patients. A further 85/369 (23%) of patients exhibited slowing in FEV₁ decline but failed to stabilize during the study. The remaining 144/369 (39%) demonstrated no appreciable response to ECP. Graft survival in the latter group was poorest, with 3-year survival of 18%. Among transient responders 3-year survival was surprisingly good at almost 75%, with almost all stabilized patients surviving 3 years. Patients commenced on ECP for restrictive allograft syndrome (RAS) did poorly. Bronchiolitis obliterans patients who subsequently developed restrictive features, subsequently developed ECP responses similar to RAS. A reliable prediction of lack of ECP response was evident after 106 [71 - 181] days. <h3>Conclusion</h3> ECP appears to offer a survival benefit in some CLAD patients. A sizeable minority of patients stabilized and this conferred the best prognosis. Any demonstrable effect on dFEV1 within 6 months of initiation may support ECP continuation. Should no change in dFEV1 occur in this period, treatment withdrawal should be considered. Restrictive phenotypes, developing either prior to or during ECP treatment confer a very poor prognosis.