Pilot study of a new online extracorporeal photopheresis system in patients with steroid refractory or dependent chronic graft vs host disease

Abstract

Background A new protocol has been developed on the Amicus Separator that enables the device to perform online extracorporeal photopheresis (ECP) procedures when used in conjunction with the Phelix photoactivation device and associated disposable kit. The objective of this study was to evaluate the safety and performance of the Amicus ECP System in adult subjects with steroid‐refractory or dependent chronic graft vs host disease (cGVHD). Study Design and Methods Eight subjects with mild to severe cGVHD underwent 31 procedures. Subject safety evaluations were performed pre and post procedure and adverse events (AEs) were recorded during treatment and 24 hours after the last procedure. In vitro evaluations of the treated cells included hematology counts and lymphocyte apoptosis, viability and proliferation as measures for ECP procedure validation. Results For n = 23 evaluable procedures, median (range) procedure time was 88 (78‐110) minutes, during which 2.9 (0.6‐4.7) × 10 9 TNCs (approximately 90% MNCs) were treated and reinfused to the subjects. All subject safety evaluations (vitals, cell counts, plasma hemoglobin and bacterial and endotoxin testing) were within expected ranges. All device or procedure related AEs were mild in nature. After 24 hours in culture, 86 (52‐98)% of treated lymphocytes were apoptotic compared to 27 (15‐51)% in controls. Inhibition of lymphocyte proliferation was >91% in all procedures. Conclusion ECP procedures were safely completed in adult subjects with SR‐cGVHD treated using the new online Amicus ECP system.

Impact of extracorporeal photopheresis on blood and coagulation parameters

“…Anticoagulation through heparins or citrate is essential for maintaining the extracorporeal blood flow on the apheresis circuit 17,18 . Heparin, which was used for ECP method in the present study, can cause prolongation of PT and the PTT by acting on the common pathway factors.…”

“…Anticoagulation through heparins or citrate is essential for maintaining the extracorporeal blood flow on the apheresis circuit. 17,18 Heparin, which was used for ECP method in the present study, can cause prolongation of PT and the PTT by acting on the common pathway factors. By contrast, the INR as another frequently used coagulation parameter is not affected by heparin directly, but can be falsely elevated by heparin due to thromboplastin test reagents.…”

“…While effective, heparin anticoagulation may be associated with an increased frequency of bleeding complications. The amount of heparin returned at the end of the first cycle of ECP can vary between patients, but is probably in the range of 1000–2000 USP units in a 2‐min period 1,18,19 . To our best knowledge, evaluation of systemic coagulation parameters in ECP patients have not been reported in the literature.…”

“…The amount of heparin returned at the end of the first cycle of ECP can vary between patients, but is probably in the range of 1000-2000 USP units in a 2-min period. 1,18,19 To our best knowledge, evaluation of systemic coagulation parameters in ECP patients have not been reported in the literature. Based on these considerations, we assessed various coagulation parameters in patients who underwent ECP, but did not observe any significant changes over time.…”

Untitled

“…Legend: Avg MNC count=(subject pre-procedure MNC + Subject post-procedure MNC)/2 and AC=anticoagulant volume. 7 Flow cytometry assessment: Three peripheral blood immunoprofiles were made by flow cytometry: at admission, at 21 and 28 days' post-transplantation (Figure 1). The pre-transplantation Neutrophil/ Lymphocytes Ratio was 1.4, and at days 21 and 28 were 3.3 and 1.5 respectively.…”