title: Response of Steroid-Refractory Acute GVHD to α1-Antitrypsin.
abstract: α1-Antitrypsin (AAT) is a serine protease inhibitor with anti-inflammatory, antiapoptotic, and immunomodulatory properties. It has therapeutic efficacy in animal models of autoimmune diseases, inflammatory disorders, and transplantation. In a phase I/II open-label single-center study, we administered AAT (Glassia; Baxalta/Kamada, New Ziona, Israel) as salvage therapy to 12 patients with steroid-refractory acute graft-versus-host disease (GVHD). AAT was given i.v. at 2 dose levels over a 15-day course. All patients had grades III or IV GVHD with stage 4 gut involvement. After treatment, plasma AAT levels increased in both cohorts and remained within 2 to 4 mg/mL for the duration of treatment. No clinically relevant toxicities attributable to AAT were observed. GVHD manifestations improved in 8 of 12 patients, and 4 responses were complete. Six patients (50%) were alive at last follow-up (>104 to >820 days). These findings show that AAT is well tolerated and has efficacy in the treatment of steroid-refractory severe acute GVHD. Further studies are warranted.
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Washington/Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: A Mario
authors.initials: AM
authors.lastname: Marcondes
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Washington/Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: David
authors.initials: D
authors.lastname: Hockenbery
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Marina
authors.initials: M
authors.lastname: Lesnikova
authors.affiliation: University of Colorado, Aurora, Colorado; Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Washington/Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: Ann
authors.initials: A
authors.lastname: Woolfrey
authors.affiliation: University of Washington/Seattle Cancer Care Alliance, Seattle, Washington; Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: Terry
authors.initials: T
authors.lastname: Gernsheimer
authors.affiliation: Baxalta US Inc., Westlake Village, California.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Loghman-Adham
authors.affiliation: Baxalta US Inc., Westlake Village, California.
authors.forename: David
authors.initials: D
authors.lastname: Gelmont
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Washington/Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: Barry
authors.initials: B
authors.lastname: Storer
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Washington/Seattle Cancer Care Alliance, Seattle, Washington.
authors.forename: John A
authors.initials: JA
authors.lastname: Hansen
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington; University of Washington/Seattle Cancer Care Alliance, Seattle, Washington. Electronic address: blarson@fhcrc.org.
authors.forename: H Joachim
authors.initials: HJ
authors.lastname: Deeg
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007410:Intestinal Diseases / Q000209:etiology; D008297:Male; D008875:Middle Aged; D016879:Salvage Therapy / Q000379:methods; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D013256:Steroids / Q000494:pharmacology / Q000627:therapeutic use; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D000515:alpha 1-Antitrypsin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D015842:Serine Proteinase Inhibitors; D013256:Steroids; D000515:alpha 1-Antitrypsin
keywords: AAT; Protease inhibitor; Steroid-refractory acute GVHD; α(1)-antitrypsin