Details

Autor(en) / Beteiligte

• Magenau, John M
• Goldstein, Steven C
• Peltier, Dan
• Soiffer, Robert J
• Braun, Thomas
• Pawarode, Attaphol
• Riwes, Mary M
• Kennel, Maggi
• Antin, Joseph H
• Cutler, Corey S
• Ho, Vincent T
• Alyea, 3rd, Edwin P
• Parkin, Brian L
• Yanik, Gregory A
• Choi, Sung Won
• Lewis, Eli C
• Dinarello, Charles A
• Koreth, John
• Reddy, Pavan

Titel

α 1 -Antitrypsin infusion for treatment of steroid-resistant acute graft-versus-host disease

Ist Teil von

• Blood, 2018-03, Vol.131 (12), p.1372

Ort / Verlag

United States

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• Corticosteroid resistance after acute graft-versus-host disease (SR-aGVHD) results in high morbidity and mortality after allogeneic hematopoietic cell transplantation. Current immunosuppressive therapies for SR-aGVHD provide marginal effectiveness because of poor response or excessive toxicity, primarily from infection. α -Antitrypsin (AAT), a naturally abundant serine protease inhibitor, is capable of suppressing experimental GVHD by downmodulating inflammation and increasing ratios of regulatory (T ) to effector T cells (T s). In this prospective multicenter clinical study, we sought to determine the safety and response rate of AAT administration in SR-aGVHD. Forty patients with a median age of 59 years received intravenous AAT twice weekly for 4 weeks as first-line treatment of SR-aGVHD. The primary end point was overall response rate (ORR), the proportion of patients with SR-aGVHD in complete (CR) or partial response 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 rates by day 28 were 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 preclinical data, correlative samples showed an increase in ratio of activated T s to T s after AAT treatment. These data suggest that AAT is safe and may be potentially efficacious in treating SR-aGVHD. This trial was registered at www.clinicaltrials.gov as #NCT01700036.