Gergoudis, Stephanie C. and DeFilipp, Zachariah and Ozbek, Umut and Sandhu, Karamjeet S. and Etra, Aaron M. and Choe, Hannah K. and Kitko, Carrie L. and Ayuk, Francis and Aziz, Mina and Baez, Janna and Ben-David, Kaitlyn and Bunworasate, Udomsak and Gandhi, Isha and Hexner, Elizabeth O. and Hogan, William J. and Holler, Ernst and Kasikis, Stelios and Kowalyk, Steven M. and Lin, Jung-Yi and Merli, Pietro and Morales, George and Nakamura, Ryotaro and Reshef, Ran and Roesler, Wolf and Srinagesh, Hrishikesh and Young, Rachel and Chen, Yi-Bin and Ferrara, James L. M. and Levine, John E. (2020) Biomarker-guided preemption of steroid-refractory graft-versus-host disease with alpha-1-antitrypsin. BLOOD ADVANCES, 4 (24). pp. 6098-6105. ISSN 2473-9529, 2473-9537
Full text not available from this repository. (Request a copy)Abstract
Steroid-refractory (SR) acute graft-versus-host disease (GVHD) remains a major cause of nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation (HCT), but its occurrence is not accurately predicted by pre-HCT clinical risk factors. The Mount Sinai Acute GVHD International Consortium (MAGIC) algorithm probability (MAP) identifies patients who are at high risk for developing SR GVHD as early as 7 days after HCT based on the extent of intestinal crypt damage as measured by the concentrations of 2 serum biomarkers, suppressor of tumorigenesis 2 and regenerating islet-derived 3 alpha. We conducted a multicenter proof-of-concept "preemptive" treatment trial of alpha-1-antitrypsin (AAT), a serine protease inhibitor with demonstrated activity against GVHD, in patients at high risk for developing SR GVHD. Patients were eligible if they possessed a high-risk MAP on day 7 after HCT or, if initially low risk, became high risk on repeat testing at day 14. Thirty high-risk patients were treated with twice-weekly infusions of AAT for a total of 16 doses, and their outcomes were compared with 90 high-risk near-contemporaneous MAGIC control patients. AAT treatment was well tolerated with few toxicities, but it did not lower the incidence of SR GVHD compared with controls (20% vs 14%, P = 5.56). We conclude that real-time biomarker-based risk assignment is feasible early after allogeneic HCT but that this dose and schedule of AAT did not change the incidence of SR acute GVHD. This trial was registered at www.clinicaltrials.gov as #NCT03459040.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HEMATOPOIETIC-CELL TRANSPLANTATION; ACUTE GVHD; MARROW-TRANSPLANTATION; CLINICAL-TRIAL; GLOBULIN; SURVIVAL; PREVENTION; PROTECTS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 05 Mar 2021 07:31 |
| Last Modified: | 05 Mar 2021 07:31 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43101 |
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