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Blood Adv. 2018 Aug 14;2(15):1882-1888. doi: 10.1182/bloodadvances.2018017343.

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

Author information

1
Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN.
2
Mayo Clinic, Phoenix, AZ.
3
Blood and Marrow Transplantation Program, The Icahn School of Medicine at Mount Sinai, New York, NY.
4
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
5
Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan.
6
Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY.
7
Department of Medicine, Weill Cornell Medical Center, New York, NY.
8
Hematologic Malignancies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
9
Division of Blood and Marrow Transplantation, Stanford University Medical Center, Stanford, CA.
10
Center for Hematologic Malignancies, Oregon Health and Science University, Portland, OR.
11
Division of Hematology/Oncology, Stem Cell Transplantation, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
12
Medical Oncology, Washington University Medical Center, St. Louis, MO.
13
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC.
14
Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI.
15
Blood and Marrow Transplantation Program, Mayo Clinic, Rochester, MN.
16
Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.
17
Department of Stem Cell Transplantation, University Medical Center, Hamburg-Eppendorf, Germany.
18
Blood and Marrow Transplantation Program, University of Regensburg, Regensburg, Germany.
19
Blood and Marrow Transplantation Program, Chulalongkorn University, Bangkok, Thailand.
20
Blood and Marrow Transplantation Program, The Ohio State University, Columbus, OH.
21
Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
22
National Marrow Donor Program, Minneapolis, MN.
23
The EMMES Corporation, Rockville, MD.
24
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD; and.
25
MD Anderson Cancer Center, Houston, TX.

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.

PMID:
30087106
PMCID:
PMC6093743
DOI:
10.1182/bloodadvances.2018017343
[Indexed for MEDLINE]
Free PMC Article

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