Blood Advances (Aug 2018)
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. Renteria,
- Gregory 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
Affiliations
- Shernan G. Holtan
- Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN;; Shernan G. Holtan, Blood and Marrow Transplant Program, University of Minnesota, 420 Delaware St SE, MMC 480, Minneapolis, MN 55455;
- Todd E. DeFor
- Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN;
- Angela Panoskaltsis-Mortari
- Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN;
- Nandita Khera
- Mayo Clinic, Phoenix, AZ;
- John E. Levine
- Blood and Marrow Transplantation Program, The Icahn School of Medicine at Mount Sinai, New York, NY;
- Mary E.D. Flowers
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;
- Stephanie J. Lee
- Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA;
- Yoshihiro Inamoto
- Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan;
- George L. Chen
- Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY;
- Sebastian Mayer
- Department of Medicine, Weill Cornell Medical Center, New York, NY;
- Mukta Arora
- Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN;
- Jeanne Palmer
- Mayo Clinic, Phoenix, AZ;
- Corey S. Cutler
- Hematologic Malignancies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA;
- Sally Arai
- Division of Blood and Marrow Transplantation, Stanford University Medical Center, Stanford, CA;
- Aleksandr Lazaryan
- Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN;
- Laura F. Newell
- Center for Hematologic Malignancies, Oregon Health and Science University, Portland, OR;
- Madan H. Jagasia
- Division of Hematology/Oncology, Stem Cell Transplantation, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN;
- Iskra Pusic
- Medical Oncology, Washington University Medical Center, St. Louis, MO;
- William A. Wood
- Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC;
- Anne S. Renteria
- Blood and Marrow Transplantation Program, The Icahn School of Medicine at Mount Sinai, New York, NY;
- Gregory Yanik
- Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI;
- William J. Hogan
- Blood and Marrow Transplantation Program, Mayo Clinic, Rochester, MN;
- Elizabeth Hexner
- Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA;
- Francis Ayuk
- Department of Stem Cell Transplantation, University Medical Center, Hamburg-Eppendorf, Germany;
- Ernst Holler
- Blood and Marrow Transplantation Program, University of Regensburg, Regensburg, Germany;
- Udomsak Bunworasate
- Blood and Marrow Transplantation Program, Chulalongkorn University, Bangkok, Thailand;
- Yvonne A. Efebera
- Blood and Marrow Transplantation Program, The Ohio State University, Columbus, OH;
- James L.M. Ferrara
- Blood and Marrow Transplantation Program, The Icahn School of Medicine at Mount Sinai, New York, NY;
- Joseph Pidala
- Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL;
- Alan Howard
- National Marrow Donor Program, Minneapolis, MN;
- Juan Wu
- The EMMES Corporation, Rockville, MD;
- Javier Bolaños-Meade
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD;
- Vincent Ho
- Division of Blood and Marrow Transplantation, Stanford University Medical Center, Stanford, CA;
- Amin Alousi
- MD Anderson Cancer Center, Houston, TX
- Bruce R. Blazar
- Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN;
- Daniel J. Weisdorf
- Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN;
- Margaret L. MacMillan
- Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN;
- Journal volume & issue
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Vol. 2,
no. 15
pp. 1882 – 1888
Abstract
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.
