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A Prospective, Multicenter Study of Closed System Extracorporeal Photopheresis for Children With Steroid-Refractory Acute Graft-Versus-Host Disease
Kitko, C. L., Abdel-Azim, H., Carpenter, P. A., Dalle, J. H., Diaz-de-Heredia, C., Gaspari, S., Gennery, A. R., Handgretinger, R., Lawitschka, A.
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND Steroid-refractory (SR) acute graft-versus-host disease (aGvHD) therapy involves intensive immunosuppression, which is associated with significant infectious risk. Extracorporeal photopheresis (ECP) is used to treat SR-aGvHD and is considered to be more immunomodulatory than immunosuppressive. However, pediatric data are mostly retrospective and often involve multi-step ECP that includes apheresis followed by separate photosensitizing/reinfusion on another device. OBJECTIVE To prospectively evaluate the efficacy and safety of a single-device ECP system in children with SR-aGvHD. STUDY DESIGN Open-label, multicenter, phase 3 study of the THERAKOS® CELLEX® Photopheresis System in children/young adults aged 1 to 21 years with SR-aGvHD. Patients were treated 3 times per week for 4 weeks, then twice weekly through week 12 while maintaining standard aGvHD prophylaxis. The primary efficacy endpoint was the proportion of patients achieving overall response (OR) at day 28 without the addition of next-line systemic treatment. Secondary endpoints included the proportion of patients achieving OR at weeks 8 and 12; the mean weekly steroid dose at weeks 4, 8, and 12; and treatment-emergent adverse events (TEAEs). RESULTS Twenty-nine children (median age, 8 years) were enrolled. OR was 55% by day 28, 74% by week 8, and 79% by week 12. Progressive improvements were observed in the skin and the gastrointestinal tract. Mean steroid dose decreased from 1.54 mg/kg/day at baseline to 0.90 mg/kg/day at week 4; 35% of patients achieved >50% steroid dose reduction at week 4 and 75% achieved >50% steroid dose reduction at week 12. Of 168 TEAEs reported among 25 patients (86%), 28 (17%) events were infections and 14 (8%) events were considered to be probably treatment related (all nonserious). Of 627 ECP treatments administered in children/young adults, 68% required blood priming. Treatment-related AEs, including hypotension, hypocalcemia, central line infection, and catheter-site bruising, were rare (1 event each). Three deaths occurred and were deemed unrelated to ECP by the investigators. CONCLUSION Use of the THERAKOS® CELLEX® Photopheresis System was effective in children with SR-aGvHD, with more than half experiencing improvement by day 28 and further responses observed over 12 weeks. Very few TEAEs were attributable to ECP, and no new safety signals were observed.