Response of Steroid-Refractory Acute GVHD to α1-Antitrypsin

Biol Blood Marrow Transplant. 2016 Sep;22(9):1596-1601. doi: 10.1016/j.bbmt.2016.05.011. Epub 2016 May 17.

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.

Keywords: AAT; Protease inhibitor; Steroid-refractory acute GVHD; α(1)-antitrypsin.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Female
  • Graft vs Host Disease / drug therapy*
  • Graft vs Host Disease / etiology
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Intestinal Diseases / etiology
  • Male
  • Middle Aged
  • Salvage Therapy / methods
  • Serine Proteinase Inhibitors / pharmacology
  • Serine Proteinase Inhibitors / therapeutic use
  • Steroids / pharmacology
  • Steroids / therapeutic use
  • Transplantation, Homologous
  • Treatment Outcome
  • alpha 1-Antitrypsin / administration & dosage
  • alpha 1-Antitrypsin / blood
  • alpha 1-Antitrypsin / pharmacology*
  • alpha 1-Antitrypsin / therapeutic use

Substances

  • Serine Proteinase Inhibitors
  • Steroids
  • alpha 1-Antitrypsin