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Amphiregulin modifies the Minnesota Acute Graft-versus-Host Disease Risk Score: results from BMT CTN 0302/0802.


ABSTRACT: 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.

SUBMITTER: Holtan SG 

PROVIDER: S-EPMC6093743 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Amphiregulin modifies the Minnesota Acute Graft-versus-Host Disease Risk Score: results from BMT CTN 0302/0802.

Holtan Shernan G SG   DeFor Todd E TE   Panoskaltsis-Mortari Angela A   Khera Nandita N   Levine John E JE   Flowers Mary E D MED   Lee Stephanie J SJ   Inamoto Yoshihiro Y   Chen George L GL   Mayer Sebastian S   Arora Mukta M   Palmer Jeanne J   Cutler Corey S CS   Arai Sally S   Lazaryan Aleksandr A   Newell Laura F LF   Jagasia Madan H MH   Pusic Iskra I   Wood William A WA   Renteria Anne S AS   Yanik Gregory G   Hogan William J WJ   Hexner Elizabeth E   Ayuk Francis F   Holler Ernst E   Bunworasate Udomsak U   Efebera Yvonne A YA   Ferrara James L M JLM   Pidala Joseph J   Howard Alan A   Wu Juan J   Bolaños-Meade Javier J   Ho Vincent V   Alousi Amin A   Blazar Bruce R BR   Weisdorf Daniel J DJ   MacMillan Margaret L ML  

Blood advances 20180801 15


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 trial  ...[more]

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