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Extracorporeal photopheresis (ECP) is an effective therapy in children with refractory graft-versus-host disease (GVHD). The two most frequently used instruments are UVAR-XTS® and CELLEX®. We performed a retrospective chart review of ten patients who underwent ECP with both UVAR-XTS® and CELLEX® instruments for steroid-refractory acute or chronic GVHD to compare instrument run times, percentages of cells treated, and complication rates. We found that compared to the UVAR-XTS® instrument, use of the CELLEX® instrument resulted in shorter run times, increased percentage of mononuclear cells treated, reduced incidence of line occlusions requiring TPA treatment, and decreased incidence of patient-related complications. Pediatr Blood Cancer 2015;62:1485–1488. © 2015 Wiley Periodicals, Inc.