α1-Antitrypsin Infusion for treatment of Steroid Resistant Acute Graft-versus-Host Disease

John M. Magenau, Steven C. Goldstein, Dan Peltier, Robert J. Soiffer, Thomas Braun, Attaphol Pawarode, Mary M. Riwes, Maggi Kennel, Joseph H. Antin, Corey S. Cutler, Vincent T. Ho, Edwin P Alyea, Brian L. Parkin, Gregory A. Yanik, Sung Won Choi, Eli C. Lewis, Charles A. Dinarello, John Koreth and Pavan Reddy

Key points

  • AAT infusion produced a high proportion of durable clinical responses in steroid-resistant acute graft-versus-host disease (SR-aGVHD).

  • AAT is associated with minimal toxicity and low rates of infection in SR-aGVHD patients who are at significant risk for mortality.


Corticosteroid resistance following acute GVHD (SR-aGVHD) results in high morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Current immunosuppressive therapies for SR-aGVHD provide marginal effectiveness due to poor response or excessive toxicity, primarily from infection. Alpha-1 antitrypsin (AAT), a naturally abundant serine protease inhibitor, is capable of suppressing experimental GVHD by down-modulation of inflammation and increasing ratios of regulatory to effector T cells. In this prospective multicenter clinical study we sought to determine the safety and response rate of AAT administration in SR-aGVHD (NCT01700036). Forty patients at a median age of 59 years received intravenous AAT twice weekly for four weeks as first line treatment for SR-aGVHD. The primary endpoint was overall response rate (ORR), the proportion of SR-aGVHD in CR+PR by day 28 without addition of further immunosuppression. Treatment was well tolerated without drug related adverse events. A significant increase in serum levels of AAT was observed after treatment. The ORR and CR rate by day 28 was 65% and 35%, respectively, and included responses in all aGVHD target organs. At day 60, responses were sustained in 73% of patients without intervening immunosuppression. Infectious-mortality was 10% at 6 months and 2.5% within 30 days of last AAT infusion. Consistent with pre-clinical data, correlative samples showed an increase in ratio of activated Tregs to effector T cells after AAT treatment. These data suggest that AAT is safe, and may be potentially efficacious in treating SR-aGVHD.

  • Submitted November 9, 2017.
  • Accepted January 24, 2018.