title: Safety and efficacy of denileukin diftitox in patients with steroid-refractory acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.
abstract: Denileukin diftitox (Ontak), a recombinant protein composed of human interleukin 2 (IL-2) fused to diphtheria toxin, has selective cytotoxicity against activated lymphocytes expressing the high-affinity IL-2 receptor. We conducted a phase 1 study of denileukin diftitox in 30 patients with steroid refractory acute graft-versus-host disease (GVHD). Seven patients received 9 microg/kg intravenously on days 1 and 15; 18 received 9 microg/kg intravenously on days 1, 3, 5, 15, 17, and 19; and 5 received 9 microg/kg intravenously on days 1 to 5 and 15 to 19. Hepatic transaminase elevation was the dose-limiting toxicity (DLT), and dose level 2 was the maximum tolerated dose (MTD). Overall, 71% of patients responded with complete resolution (12 of 24; 50%) or partial resolution (5 of 24; 21%) of GVHD. Eight of 24 patients (33%) are alive at 6.3 to 24.6 months (median, 7.2 months). Denileukin diftitox is tolerable and has promising activity in steroid-refractory acute GVHD.
authors.affiliation: Dana-Farber Cancer Institute, 44 Binney St, D1B21, Boston, MA 02115, USA. vtho@partners.org
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Ho
authors.forename: David
authors.initials: D
authors.lastname: Zahrieh
authors.forename: Ephraim
authors.initials: E
authors.lastname: Hochberg
authors.forename: Eileen
authors.initials: E
authors.lastname: Micale
authors.forename: Jesse
authors.initials: J
authors.lastname: Levin
authors.forename: Carol
authors.initials: C
authors.lastname: Reynolds
authors.forename: Steve
authors.initials: S
authors.lastname: Steckel
authors.forename: Corey
authors.initials: C
authors.lastname: Cutler
authors.forename: David C
authors.initials: DC
authors.lastname: Fisher
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Alyea
authors.forename: Jerome
authors.initials: J
authors.lastname: Ritz
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Soiffer
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Antin
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D004167:Diphtheria Toxin / Q000008:administration & dosage* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000633:toxicity; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000633:toxicity; D016879:Salvage Therapy; D013256:Steroids; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D004167:Diphtheria Toxin; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D013256:Steroids; C078456:denileukin diftitox