Lung transplantation has become the treatment of choice for selected patients with end-stage lung disease.
However, according to the International Society of Heart and Lung Transplantation, the average patient survives just 5 years after transplantation, due primarily to chronic rejection of the transplant. The histologic hallmark of chronic rejection after lung transplantation is obliterative bronchiolitis, a fibroproliferative scarring process that involves the respiratory and membranous bronchioles, resulting in narrowing of the airway lumen and ultimately complete luminal obliteration. Physiologically and clinically, this luminal narrowing results in airflow limitation and breathlessness. Bronchiolitis Obliterans Syndrome (BOS) is the leading cause of death beyond the first year after transplantation.
The management of BOS includes optimizing immunosuppressive drugs. At some centers, a procedure called Extracorporeal Photopheresis (ECP) has been used as a salvage treatment for progressive BOS with favorable clinical results in many cases. ECP involves separating the patient’s blood into a leukocyte-enriched component (buffy coat) and a leukocyte-depleted component. The buffy coat is then photosensitized with 8-methoxypsoralen and treated with ultraviolet light within a photosensitization chamber, and reinfused into the patient’s circulation. This process is thought to result in alterations in antigen presenting cells, cytokine profiles, and the expansion of regulatory T cells. Multiple small case series as well as a couple of larger case series (e.g. one from Washington University involving 60 patients) have described a reduction or stabilization in the rate of decline in lung function after the initiation of ECP for progressive BOS. Studies indicate that ECP is often effective in the majority of patients with respect to preventing further lung damage from BOS.
However, what is not understood at this time is which patients are most likely to benefit from ECP treatment – specifically, whether certain co-existing disease states or patient-related demographic, functional, treatment-related or diagnostic variables might prove to have predictive value in identifying who will respond to the treatment. This represents the primary rationale for conducting this study.
On May 2, 2012, CMS issued a Decision Memo stating that ECP is covered for Medicare beneficiaries for the treatment of BOS following lung transplantation only when the procedure is provided under a clinical research study. Washington University investigators led by Dr. George Despotis developed the ECP Trial as a way to capture important information about the use of ECP in multiple centers to confirm the overall effectiveness of the treatment in multiple sites and to identify any factors that predict which patients will benefit from this therapy.