title: Progressive improvement in cutaneous and extracutaneous chronic graft-versus-host disease after a 24-week course of extracorporeal photopheresis--results of a crossover randomized study.
abstract: In a prior multicenter randomized controlled trial, we found that a 12-week course of extracorporeal photopheresis (ECP) plus standard immunosuppressive therapy resulted in several beneficial outcomes in patients with corticosteroid-refractory/intolerant/dependent chronic graft-versus-host disease (GVHD). Here, we report the results of an open-label crossover ECP study in 29 eligible participants randomized initially to the standard of care non-ECP (control) arm. Eligible for the crossover ECP study were control arm patients who either (1) had progression of cutaneous chronic GVHD (cGVHD), defined as >25% worsening from baseline as measured by the percent change in the total skin score (TSS) at any time, or (2) had less than 15% improvement in the TSS, or had a ≤25% reduction in corticosteroid dose at week 12 of the initial study. ECP was administered 3 times during week 1, then twice weekly until week 12, followed by 2 treatments monthly until week 24. The median age of the study cohort was 43 (20-67) years and 90% had extensive cGVHD. The median months from onset of cGVHD to start of ECP were 26 (range: 4-79). Twenty-five of 29 patients (86%) completed the 24-week course of ECP. Complete or partial skin response at week 24 was noted in 9 patients (31%). The median percent of decrease in TSS from baseline to weeks 12 and 24 was -7.9 and -25.8, respectively. In 4 (17%) and 8 (33%) patients, a ≥50% reduction in corticosteroid dose at weeks 12 and 24 was observed. Extracutaneous cGVHD response was highest in oral mucosa with 70% complete and partial resolution after week 24. In conclusion, progressive improvement in cutaneous and extracutaneous cGVHD was observed after a 24-week course of ECP in patients who previously had no clinical improvement or exhibited worsening of cGVHD while receiving standard immunosuppressive therapy alone in a randomized study. These results confirm previous findings and support the notion that prolonged ECP appears to be necessary for optimal therapeutic effects in corticosteroid-refractory cGVHD patients.
authors.affiliation: Medical University of Vienna, Departments of Internal Medicine I and Dermatology, Vienna, Austria. Hildegard.greinix@meduniwien.ac.at
authors.forename: Hildegard T
authors.initials: HT
authors.lastname: Greinix
authors.forename: Koen
authors.initials: K
authors.lastname: van Besien
authors.forename: Ahmet H
authors.initials: AH
authors.lastname: Elmaagacli
authors.forename: Uwe
authors.initials: U
authors.lastname: Hillen
authors.forename: Andrew
authors.initials: A
authors.lastname: Grigg
authors.forename: Robert
authors.initials: R
authors.lastname: Knobler
authors.forename: Dennis
authors.initials: D
authors.lastname: Parenti
authors.forename: Vijay
authors.initials: V
authors.lastname: Reddy
authors.forename: Koen
authors.initials: K
authors.lastname: Theunissen
authors.forename: Mauricette
authors.initials: M
authors.lastname: Michallet
authors.forename: Mary E D
authors.initials: ME
authors.lastname: Flowers
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors; D018592:Cross-Over Studies; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D017893:Photopheresis / Q000379:methods*; D012871:Skin Diseases / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D065095:Calcineurin Inhibitors; D009173:Mycophenolic Acid