Amphiregulin modifies the Minnesota Acute Graft-versus-Host Disease Risk Score
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Amphiregulin modifies the Minnesota Acute Graft-versus-Host Disease Risk Score : results from BMT CTN 0302/0802. / Holtan, Shernan G; DeFor, Todd E; Panoskaltsis-Mortari, Angela; Khera, Nandita; Levine, John E; Flowers, Mary E D; Lee, Stephanie J; Inamoto, Yoshihiro; Chen, George L; Mayer, Sebastian; Arora, Mukta; Palmer, Jeanne; Cutler, Corey S; Arai, Sally; Lazaryan, Aleksandr; Newell, Laura F; Jagasia, Madan H; Pusic, Iskra; Wood, William A; Renteria, Anne S; Yanik, Gregory; Hogan, William J; Hexner, Elizabeth; Ayuk, Francis; Holler, Ernst; Bunworasate, Udomsak; Efebera, Yvonne A; Ferrara, James L M; Pidala, Joseph; Howard, Alan; Wu, Juan; Bolaños-Meade, Javier; Ho, Vincent; Alousi, Amin; Blazar, Bruce R; Weisdorf, Daniel J; MacMillan, Margaret L.
In: BLOOD ADV, Vol. 2, No. 15, 14.08.2018, p. 1882-1888.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Amphiregulin modifies the Minnesota Acute Graft-versus-Host Disease Risk Score
T2 - results from BMT CTN 0302/0802
AU - Holtan, Shernan G
AU - DeFor, Todd E
AU - Panoskaltsis-Mortari, Angela
AU - Khera, Nandita
AU - Levine, John E
AU - Flowers, Mary E D
AU - Lee, Stephanie J
AU - Inamoto, Yoshihiro
AU - Chen, George L
AU - Mayer, Sebastian
AU - Arora, Mukta
AU - Palmer, Jeanne
AU - Cutler, Corey S
AU - Arai, Sally
AU - Lazaryan, Aleksandr
AU - Newell, Laura F
AU - Jagasia, Madan H
AU - Pusic, Iskra
AU - Wood, William A
AU - Renteria, Anne S
AU - Yanik, Gregory
AU - Hogan, William J
AU - Hexner, Elizabeth
AU - Ayuk, Francis
AU - Holler, Ernst
AU - Bunworasate, Udomsak
AU - Efebera, Yvonne A
AU - Ferrara, James L M
AU - Pidala, Joseph
AU - Howard, Alan
AU - Wu, Juan
AU - Bolaños-Meade, Javier
AU - Ho, Vincent
AU - Alousi, Amin
AU - Blazar, Bruce R
AU - Weisdorf, Daniel J
AU - MacMillan, Margaret L
N1 - © 2018 by The American Society of Hematology.
PY - 2018/8/14
Y1 - 2018/8/14
N2 - Amphiregulin (AREG) is an epidermal growth factor receptor ligand that can restore integrity to damaged intestinal mucosa in murine models of acute graft-versus-host disease (aGVHD). We previously reported that circulating AREG is elevated in late-onset aGVHD (occurring after 100 days posttransplant), but its clinical relevance in the context of aGVHD risk is unknown. We measured AREG in 251 aGVHD onset blood samples from Blood and Marrow Clinical Trials Network (BMT CTN) primary treatment trials and determined their association with GVHD severity, day 28 complete or partial response (CR/PR) to first-line therapy, overall survival (OS), and nonrelapse mortality (NRM). Every doubling of plasma AREG was associated with a 33% decrease in the odds of day 28 CR/PR (odds ratio [OR], 0.67; P < .01). An AREG threshold of 33 pg/mL or greater divided patients with Minnesota standard-risk (SR) aGVHD into a distinct group with a significantly lower likelihood of: day 28 CR/PR (72% vs 85%; P = .02); greater 2-year NRM (42% vs 15%; P < .01); and inferior OS (40% vs 66%; P < .01). High AREG ≥ 33 pg/mL also stratified patients with Minnesota high-risk (HR) aGVHD: day 28 CR/PR (54% vs 83%; P = .03) and 2-year NRM (53% vs 11%; P < .01), with a trend toward inferior 2-year OS (37% vs 60%; P = .09). High-circulating AREG (≥33 pg/mL) reclassifies patients into HR subgroups and thereby further refines the Minnesota aGVHD clinical risk score.
AB - Amphiregulin (AREG) is an epidermal growth factor receptor ligand that can restore integrity to damaged intestinal mucosa in murine models of acute graft-versus-host disease (aGVHD). We previously reported that circulating AREG is elevated in late-onset aGVHD (occurring after 100 days posttransplant), but its clinical relevance in the context of aGVHD risk is unknown. We measured AREG in 251 aGVHD onset blood samples from Blood and Marrow Clinical Trials Network (BMT CTN) primary treatment trials and determined their association with GVHD severity, day 28 complete or partial response (CR/PR) to first-line therapy, overall survival (OS), and nonrelapse mortality (NRM). Every doubling of plasma AREG was associated with a 33% decrease in the odds of day 28 CR/PR (odds ratio [OR], 0.67; P < .01). An AREG threshold of 33 pg/mL or greater divided patients with Minnesota standard-risk (SR) aGVHD into a distinct group with a significantly lower likelihood of: day 28 CR/PR (72% vs 85%; P = .02); greater 2-year NRM (42% vs 15%; P < .01); and inferior OS (40% vs 66%; P < .01). High AREG ≥ 33 pg/mL also stratified patients with Minnesota high-risk (HR) aGVHD: day 28 CR/PR (54% vs 83%; P = .03) and 2-year NRM (53% vs 11%; P < .01), with a trend toward inferior 2-year OS (37% vs 60%; P = .09). High-circulating AREG (≥33 pg/mL) reclassifies patients into HR subgroups and thereby further refines the Minnesota aGVHD clinical risk score.
KW - Journal Article
U2 - 10.1182/bloodadvances.2018017343
DO - 10.1182/bloodadvances.2018017343
M3 - SCORING: Journal article
C2 - 30087106
VL - 2
SP - 1882
EP - 1888
JO - BLOOD ADV
JF - BLOOD ADV
SN - 2473-9529
IS - 15
ER -