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Biomarker-guided preemption of steroid-refractory graft-versus-host disease with α-1-antitrypsin

Standard

Biomarker-guided preemption of steroid-refractory graft-versus-host disease with α-1-antitrypsin. / Gergoudis, Stephanie C; DeFilipp, Zachariah; Özbek, Umut; Sandhu, Karamjeet S; Etra, Aaron M; Choe, Hannah K; Kitko, Carrie L; Ayuk, Francis; Aziz, Mina; Baez, Janna; Ben-David, Kaitlyn; Bunworasate, Udomsak; Gandhi, Isha; Hexner, Elizabeth O; Hogan, William J; Holler, Ernst; Kasikis, Stelios; Kowalyk, Steven M; Lin, Jung-Yi; Merli, Pietro; Morales, George; Nakamura, Ryotaro; Reshef, Ran; Rösler, Wolf; Srinagesh, Hrishikesh; Young, Rachel; Chen, Yi-Bin; Ferrara, James L M; Levine, John E.

in: Blood Adv, Jahrgang 4, Nr. 24, 22.12.2020, S. 6098-6105.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Gergoudis, SC, DeFilipp, Z, Özbek, U, Sandhu, KS, Etra, AM, Choe, HK, Kitko, CL, Ayuk, F, Aziz, M, Baez, J, Ben-David, K, Bunworasate, U, Gandhi, I, Hexner, EO, Hogan, WJ, Holler, E, Kasikis, S, Kowalyk, SM, Lin, J-Y, Merli, P, Morales, G, Nakamura, R, Reshef, R, Rösler, W, Srinagesh, H, Young, R, Chen, Y-B, Ferrara, JLM & Levine, JE 2020, 'Biomarker-guided preemption of steroid-refractory graft-versus-host disease with α-1-antitrypsin', Blood Adv, Jg. 4, Nr. 24, S. 6098-6105. https://doi.org/10.1182/bloodadvances.2020003336

APA

Gergoudis, S. C., DeFilipp, Z., Özbek, U., Sandhu, K. S., Etra, A. M., Choe, H. K., Kitko, C. L., Ayuk, F., Aziz, M., Baez, J., Ben-David, K., Bunworasate, U., Gandhi, I., Hexner, E. O., Hogan, W. J., Holler, E., Kasikis, S., Kowalyk, S. M., Lin, J-Y., ... Levine, J. E. (2020). Biomarker-guided preemption of steroid-refractory graft-versus-host disease with α-1-antitrypsin. Blood Adv, 4(24), 6098-6105. https://doi.org/10.1182/bloodadvances.2020003336

Vancouver

Gergoudis SC, DeFilipp Z, Özbek U, Sandhu KS, Etra AM, Choe HK et al. Biomarker-guided preemption of steroid-refractory graft-versus-host disease with α-1-antitrypsin. Blood Adv. 2020 Dez 22;4(24):6098-6105. https://doi.org/10.1182/bloodadvances.2020003336

Bibtex

@article{00d2a5d8ff744097ab3c44098b2fcd31,
title = "Biomarker-guided preemption of steroid-refractory graft-versus-host disease with α-1-antitrypsin",
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 3α. We conducted a multicenter proof-of-concept {"}preemptive{"} treatment trial of α-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 = .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.",
author = "Gergoudis, {Stephanie C} and Zachariah DeFilipp and Umut {\"O}zbek and Sandhu, {Karamjeet S} and Etra, {Aaron M} and Choe, {Hannah K} and Kitko, {Carrie L} and Francis Ayuk and Mina Aziz and Janna Baez and Kaitlyn Ben-David and Udomsak Bunworasate and Isha Gandhi and Hexner, {Elizabeth O} and Hogan, {William J} and Ernst Holler and Stelios Kasikis and Kowalyk, {Steven M} and Jung-Yi Lin and Pietro Merli and George Morales and Ryotaro Nakamura and Ran Reshef and Wolf R{\"o}sler and Hrishikesh Srinagesh and Rachel Young and Yi-Bin Chen and Ferrara, {James L M} and Levine, {John E}",
note = "{\textcopyright} 2020 by The American Society of Hematology.",
year = "2020",
month = dec,
day = "22",
doi = "10.1182/bloodadvances.2020003336",
language = "English",
volume = "4",
pages = "6098--6105",
journal = "BLOOD ADV",
issn = "2473-9529",
publisher = "Elsevier BV",
number = "24",

}

RIS

TY - JOUR

T1 - Biomarker-guided preemption of steroid-refractory graft-versus-host disease with α-1-antitrypsin

AU - Gergoudis, Stephanie C

AU - DeFilipp, Zachariah

AU - Özbek, Umut

AU - Sandhu, Karamjeet S

AU - Etra, Aaron M

AU - Choe, Hannah K

AU - Kitko, Carrie L

AU - Ayuk, Francis

AU - Aziz, Mina

AU - Baez, Janna

AU - Ben-David, Kaitlyn

AU - Bunworasate, Udomsak

AU - Gandhi, Isha

AU - Hexner, Elizabeth O

AU - Hogan, William J

AU - Holler, Ernst

AU - Kasikis, Stelios

AU - Kowalyk, Steven M

AU - Lin, Jung-Yi

AU - Merli, Pietro

AU - Morales, George

AU - Nakamura, Ryotaro

AU - Reshef, Ran

AU - Rösler, Wolf

AU - Srinagesh, Hrishikesh

AU - Young, Rachel

AU - Chen, Yi-Bin

AU - Ferrara, James L M

AU - Levine, John E

N1 - © 2020 by The American Society of Hematology.

PY - 2020/12/22

Y1 - 2020/12/22

N2 - 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 3α. We conducted a multicenter proof-of-concept "preemptive" treatment trial of α-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 = .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.

AB - 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 3α. We conducted a multicenter proof-of-concept "preemptive" treatment trial of α-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 = .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.

U2 - 10.1182/bloodadvances.2020003336

DO - 10.1182/bloodadvances.2020003336

M3 - SCORING: Journal article

C2 - 33351103

VL - 4

SP - 6098

EP - 6105

JO - BLOOD ADV

JF - BLOOD ADV

SN - 2473-9529

IS - 24

ER -