title: Denileukin diftitox for the treatment of steroid-resistant acute graft-versus-host disease.
abstract: Acute graft-versus-host disease (aGVHD) is partly mediated through activated T cells, and these cells are known to express the high-affinity receptor for interleukin 2 (IL-2R). Denileukin diftitox is composed of human IL-2 and diphtheria toxin that is cytotoxic to activated lymphocytes expressing the high-affinity IL-2R. We describe the results of a phase II study of denileukin diftitox in 22 patients with steroid-resistant aGVHD. Twenty patients were treated at dose level 1 (4.5 microg/kg daily on days 1-5 and then weekly on study days 8, 15, 22, and 29), and 2 patients were treated at dose level 2 (9.0 microg/kg delivered on the same schedule). Dose level 2 was associated with grade 3/4 renal and hepatic toxicity and vascular leak syndrome, and no further patients were treated at this level. Dose level 1 was generally well tolerated. The response of aGVHD was assessed at study days 36 and 100. Nine patients (41%) responded, all with a complete response at study day 36, and 6 patients (27%) responded at study day 100 (4 complete responses and 2 partial responses). Denileukin diftitox has promising activity in steroid-resistant aGVHD, and further study is warranted.
authors.affiliation: Texas Transplant Institute, San Antonio 78229, USA. Paul.Shaughnessy@MHShealth.com
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Shaughnessy
authors.forename: Carlos
authors.initials: C
authors.lastname: Bachier
authors.forename: Michael
authors.initials: M
authors.lastname: Grimley
authors.forename: Cesar O
authors.initials: CO
authors.lastname: Freytes
authors.forename: Natalie S
authors.initials: NS
authors.lastname: Callander
authors.forename: James H
authors.initials: JH
authors.lastname: Essell
authors.forename: Neal
authors.initials: N
authors.lastname: Flomenberg
authors.forename: George
authors.initials: G
authors.lastname: Selby
authors.forename: C F
authors.initials: CF
authors.lastname: Lemaistre
mesh_terms: D000208:Acute Disease; D019559:Capillary Leak Syndrome / Q000139:chemically induced; D056486:Chemical and Drug Induced Liver Injury; D004167:Diphtheria Toxin / Q000008:administration & dosage* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004351:Drug Resistance; D006086:Graft vs Host Disease / Q000188:drug therapy*; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000633:toxicity; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000633:toxicity; D012074:Remission Induction; D013256:Steroids
chemical_list: D004167:Diphtheria Toxin; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D013256:Steroids; C078456:denileukin diftitox