title: OKT3 muromonab as second-line and subsequent treatment in recipients of stem cell allografts with steroid-resistant acute graft-versus-host disease.
abstract: We retrospectively evaluated response to monoclonal antibody directed against CD3 (OKT3) treatment in 43 patients with steroid-resistant acute graft-versus-host disease (aGvHD) following allogeneic hematopoietic cell transplantation. Median duration of OKT3 therapy was 9 (range, 1-20) days. In all, 20 cycles were administered as second-line and 28 as third-plus line treatment. Side effects were mild to moderate. Overall response rate was 69 with 12% complete remissions and best response in skin involvement. Proportional reduction of concomitant steroids was higher in responding patients. Five patients (12%) achieved durable responses. Pharmacokinetic studies of OKT3 showed adequate plasma levels (> or = 1000 ng/ml) in 13 of 17 evaluable patients after a median of 6 (1-11) days on treatment. OKT3 became undetectable shortly after discontinuation of therapy. Median survival for all patients was 80 (2 to 2474+) days. There was a trend for better survival for patients on second-line vs third-plus line treatment (146 vs 46 days; P=0.07) and significant longer survival for patients with grade II when compared to those with grade III/IV aGvHD (206 vs 47 days; P=0.039). We conclude that salvage treatment with OKT3 shows considerable efficiency, however, sometimes of transient nature, and is well tolerated in patients with corticosteroid-resistant aGvHD.
authors.affiliation: Department of Hematology and Oncology, Wuerzburg University Hospital, Wuerzburg, Germany. knop_s@medizin.uni-wuerzburg.de
authors.forename: S
authors.initials: S
authors.lastname: Knop
authors.forename: H
authors.initials: H
authors.lastname: Hebart
authors.forename: H
authors.initials: H
authors.lastname: Gscheidle
authors.forename: E
authors.initials: E
authors.lastname: Holler
authors.forename: H-J
authors.initials: HJ
authors.lastname: Kolb
authors.forename: D
authors.initials: D
authors.lastname: Niederwieser
authors.forename: H
authors.initials: H
authors.lastname: Einsele
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D018572:Disease-Free Survival; D004351:Drug Resistance / Q000187:drug effects*; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D006801:Humans; D007938:Leukemia / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000008:administration & dosage*; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods
chemical_list: D000305:Adrenal Cortex Hormones; D016853:Muromonab-CD3