Amphiregulin modifies the Minnesota acute graft-versus-host disease risk score: Results from BMT CTN 0302/0802

Shernan G. Holtan, Todd E. DeFor, Angela Panoskaltsis-Mortari, Nandita Khera, John E. Levine, Mary E.D. Flowers, Stephanie J. Lee, Yoshihiro Inamoto, George L. Chen, Sebastian Mayer, Mukta Arora, Jeanne Palmer, Corey S. Cutler, Sally Arai, Aleksandr Lazaryan, Laura F. Newell, Madan H. Jagasia, Iskra Pusic, William A. Wood, Anne S. RenteriaGregory Yanik, William J. Hogan, Elizabeth Hexner, Francis Ayuk, Ernst Holler, Udomsak Bunworasate, Yvonne A. Efebera, James L.M. Ferrara, Joseph Pidala, Alan Howard, Juan Wu, Javier Bolaños-Meade, Vincent Ho, Amin Alousi, Bruce R. Blazar, Daniel J. Weisdorf, Margaret L. MacMillan

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 5 .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 5 .03) and 2-year NRM (53% vs 11%; P, .01), with a trend toward inferior 2-year OS (37% vs 60%; P 5 .09). High-circulating AREG ($33 pg/mL) reclassifies patients into HR subgroups and thereby further refines the Minnesota aGVHD clinical risk score.

Original languageEnglish (US)
Pages (from-to)1882-1888
Number of pages7
JournalBlood Advances
Volume2
Issue number15
DOIs
StatePublished - Aug 14 2018

Fingerprint

Graft vs Host Disease
Survival
Mortality
Intestinal Mucosa
trans-crotonin
Amphiregulin
Epidermal Growth Factor Receptor
Bone Marrow
Odds Ratio
Clinical Trials
Ligands
Therapeutics

Cite this

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 Advances, Vol. 2, No. 15, 14.08.2018, p. 1882-1888.

Research output: Contribution to journalArticle

Holtan, SG, DeFor, TE, Panoskaltsis-Mortari, A, Khera, N, Levine, JE, Flowers, MED, Lee, SJ, Inamoto, Y, Chen, GL, Mayer, S, Arora, M, Palmer, J, Cutler, CS, Arai, S, Lazaryan, A, Newell, LF, Jagasia, MH, Pusic, I, Wood, WA, Renteria, AS, Yanik, G, Hogan, WJ, Hexner, E, Ayuk, F, Holler, E, Bunworasate, U, Efebera, YA, Ferrara, JLM, Pidala, J, Howard, A, Wu, J, Bolaños-Meade, J, Ho, V, Alousi, A, Blazar, BR, Weisdorf, DJ & MacMillan, ML 2018, 'Amphiregulin modifies the Minnesota acute graft-versus-host disease risk score: Results from BMT CTN 0302/0802', Blood Advances, vol. 2, no. 15, pp. 1882-1888. https://doi.org/10.1182/bloodadvances.2018017343
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. / Amphiregulin modifies the Minnesota acute graft-versus-host disease risk score : Results from BMT CTN 0302/0802. In: Blood Advances. 2018 ; Vol. 2, No. 15. pp. 1882-1888.
@article{6f96b5825c624b76a18c52a46e642983,
title = "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 5 .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 5 .03) and 2-year NRM (53{\%} vs 11{\%}; P, .01), with a trend toward inferior 2-year OS (37{\%} vs 60{\%}; P 5 .09). High-circulating AREG ($33 pg/mL) reclassifies patients into HR subgroups and thereby further refines the Minnesota aGVHD clinical risk score.",
author = "Holtan, {Shernan G.} and DeFor, {Todd E.} and Angela Panoskaltsis-Mortari and Nandita Khera and Levine, {John E.} and Flowers, {Mary E.D.} and Lee, {Stephanie J.} and Yoshihiro Inamoto and Chen, {George L.} and Sebastian Mayer and Mukta Arora and Jeanne Palmer and Cutler, {Corey S.} and Sally Arai and Aleksandr Lazaryan and Newell, {Laura F.} and Jagasia, {Madan H.} and Iskra Pusic and Wood, {William A.} and Renteria, {Anne S.} and Gregory Yanik and Hogan, {William J.} and Elizabeth Hexner and Francis Ayuk and Ernst Holler and Udomsak Bunworasate and Efebera, {Yvonne A.} and Ferrara, {James L.M.} and Joseph Pidala and Alan Howard and Juan Wu and Javier Bola{\~n}os-Meade and Vincent Ho and Amin Alousi and Blazar, {Bruce R.} and Weisdorf, {Daniel J.} and MacMillan, {Margaret L.}",
year = "2018",
month = "8",
day = "14",
doi = "10.1182/bloodadvances.2018017343",
language = "English (US)",
volume = "2",
pages = "1882--1888",
journal = "Blood advances",
issn = "2473-9529",
publisher = "American Society of Hematology",
number = "15",

}

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.

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 5 .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 5 .03) and 2-year NRM (53% vs 11%; P, .01), with a trend toward inferior 2-year OS (37% vs 60%; P 5 .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 5 .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 5 .03) and 2-year NRM (53% vs 11%; P, .01), with a trend toward inferior 2-year OS (37% vs 60%; P 5 .09). High-circulating AREG ($33 pg/mL) reclassifies patients into HR subgroups and thereby further refines the Minnesota aGVHD clinical risk score.

UR - http://www.scopus.com/inward/record.url?scp=85058518379&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058518379&partnerID=8YFLogxK

U2 - 10.1182/bloodadvances.2018017343

DO - 10.1182/bloodadvances.2018017343

M3 - Article

C2 - 30087106

AN - SCOPUS:85058518379

VL - 2

SP - 1882

EP - 1888

JO - Blood advances

JF - Blood advances

SN - 2473-9529

IS - 15

ER -