PMID- 30087106
OWN - NLM
STAT- MEDLINE
DCOM- 20190403
LR  - 20230928
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 2
IP  - 15
DP  - 2018 Aug 14
TI  - Amphiregulin modifies the Minnesota Acute Graft-versus-Host Disease Risk Score: 
      results from BMT CTN 0302/0802.
PG  - 1882-1888
LID - 10.1182/bloodadvances.2018017343 [doi]
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.
CI  - (c) 2018 by The American Society of Hematology.
FAU - Holtan, Shernan G
AU  - Holtan SG
AD  - Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN.
FAU - DeFor, Todd E
AU  - DeFor TE
AD  - Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN.
FAU - Panoskaltsis-Mortari, Angela
AU  - Panoskaltsis-Mortari A
AD  - Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN.
FAU - Khera, Nandita
AU  - Khera N
AD  - Mayo Clinic, Phoenix, AZ.
FAU - Levine, John E
AU  - Levine JE
AD  - Blood and Marrow Transplantation Program, The Icahn School of Medicine at Mount 
      Sinai, New York, NY.
FAU - Flowers, Mary E D
AU  - Flowers MED
AD  - Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
FAU - Lee, Stephanie J
AU  - Lee SJ
AD  - Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
FAU - Inamoto, Yoshihiro
AU  - Inamoto Y
AD  - Department of Hematopoietic Stem Cell Transplantation, National Cancer Center 
      Hospital, Tokyo, Japan.
FAU - Chen, George L
AU  - Chen GL
AD  - Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY.
FAU - Mayer, Sebastian
AU  - Mayer S
AD  - Department of Medicine, Weill Cornell Medical Center, New York, NY.
FAU - Arora, Mukta
AU  - Arora M
AD  - Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN.
FAU - Palmer, Jeanne
AU  - Palmer J
AD  - Mayo Clinic, Phoenix, AZ.
FAU - Cutler, Corey S
AU  - Cutler CS
AD  - Hematologic Malignancies, Dana-Farber Cancer Institute, Harvard Medical School, 
      Boston, MA.
FAU - Arai, Sally
AU  - Arai S
AD  - Division of Blood and Marrow Transplantation, Stanford University Medical Center, 
      Stanford, CA.
FAU - Lazaryan, Aleksandr
AU  - Lazaryan A
AD  - Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN.
FAU - Newell, Laura F
AU  - Newell LF
AD  - Center for Hematologic Malignancies, Oregon Health and Science University, 
      Portland, OR.
FAU - Jagasia, Madan H
AU  - Jagasia MH
AD  - Division of Hematology/Oncology, Stem Cell Transplantation, Department of 
      Medicine, Vanderbilt University Medical Center, Nashville, TN.
FAU - Pusic, Iskra
AU  - Pusic I
AD  - Medical Oncology, Washington University Medical Center, St. Louis, MO.
FAU - Wood, William A
AU  - Wood WA
AD  - Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel 
      Hill, NC.
FAU - Renteria, Anne S
AU  - Renteria AS
AD  - Blood and Marrow Transplantation Program, The Icahn School of Medicine at Mount 
      Sinai, New York, NY.
FAU - Yanik, Gregory
AU  - Yanik G
AD  - Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI.
FAU - Hogan, William J
AU  - Hogan WJ
AD  - Blood and Marrow Transplantation Program, Mayo Clinic, Rochester, MN.
FAU - Hexner, Elizabeth
AU  - Hexner E
AD  - Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.
FAU - Ayuk, Francis
AU  - Ayuk F
AD  - Department of Stem Cell Transplantation, University Medical Center, 
      Hamburg-Eppendorf, Germany.
FAU - Holler, Ernst
AU  - Holler E
AD  - Blood and Marrow Transplantation Program, University of Regensburg, Regensburg, 
      Germany.
FAU - Bunworasate, Udomsak
AU  - Bunworasate U
AD  - Blood and Marrow Transplantation Program, Chulalongkorn University, Bangkok, 
      Thailand.
FAU - Efebera, Yvonne A
AU  - Efebera YA
AD  - Blood and Marrow Transplantation Program, The Ohio State University, Columbus, 
      OH.
FAU - Ferrara, James L M
AU  - Ferrara JLM
AD  - Blood and Marrow Transplantation Program, The Icahn School of Medicine at Mount 
      Sinai, New York, NY.
FAU - Pidala, Joseph
AU  - Pidala J
AD  - Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research 
      Institute, Tampa, FL.
FAU - Howard, Alan
AU  - Howard A
AD  - National Marrow Donor Program, Minneapolis, MN.
FAU - Wu, Juan
AU  - Wu J
AD  - The EMMES Corporation, Rockville, MD.
FAU - Bolanos-Meade, Javier
AU  - Bolanos-Meade J
AD  - Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, 
      MD; and.
FAU - Ho, Vincent
AU  - Ho V
AD  - Division of Blood and Marrow Transplantation, Stanford University Medical Center, 
      Stanford, CA.
FAU - Alousi, Amin
AU  - Alousi A
AD  - MD Anderson Cancer Center, Houston, TX.
FAU - Blazar, Bruce R
AU  - Blazar BR
AD  - Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN.
FAU - Weisdorf, Daniel J
AU  - Weisdorf DJ
AD  - Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN.
FAU - MacMillan, Margaret L
AU  - MacMillan ML
AD  - Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN.
LA  - eng
GR  - U10 HL069294/HL/NHLBI NIH HHS/United States
GR  - U01 HL069310/HL/NHLBI NIH HHS/United States
GR  - UG1 HL069290/HL/NHLBI NIH HHS/United States
GR  - P01 CA015396/CA/NCI NIH HHS/United States
GR  - R01 HL118979/HL/NHLBI NIH HHS/United States
GR  - U54 CA163438/CA/NCI NIH HHS/United States
GR  - U10 HL069330/HL/NHLBI NIH HHS/United States
GR  - UG1 HL069278/HL/NHLBI NIH HHS/United States
GR  - UG1 HL109137/HL/NHLBI NIH HHS/United States
GR  - UG1 HL069330/HL/NHLBI NIH HHS/United States
GR  - R01 CA118953/CA/NCI NIH HHS/United States
GR  - P01 CA039542/CA/NCI NIH HHS/United States
GR  - U01 CA118953/CA/NCI NIH HHS/United States
GR  - UG1 HL069249/HL/NHLBI NIH HHS/United States
GR  - UL1 TR002494/TR/NCATS NIH HHS/United States
GR  - P01 CA065493/CA/NCI NIH HHS/United States
GR  - U24 CA076518/CA/NCI NIH HHS/United States
GR  - U24 HL138660/HL/NHLBI NIH HHS/United States
GR  - U10 HL069310/HL/NHLBI NIH HHS/United States
GR  - R37 AI034495/AI/NIAID NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood Adv
JT  - Blood advances
JID - 101698425
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Amphiregulin/*blood
MH  - Disease-Free Survival
MH  - Female
MH  - Graft vs Host Disease/*blood/*mortality/therapy
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Minnesota
MH  - Risk Assessment
MH  - Severity of Illness Index
MH  - Survival Rate
PMC - PMC6093743
COIS- Conflict-of-interest disclosure: The authors declare no competing financial 
      interests.
EDAT- 2018/08/09 06:00
MHDA- 2019/04/04 06:00
PMCR- 2018/08/07
CRDT- 2018/08/09 06:00
PHST- 2018/02/12 00:00 [received]
PHST- 2018/06/26 00:00 [accepted]
PHST- 2018/08/09 06:00 [entrez]
PHST- 2018/08/09 06:00 [pubmed]
PHST- 2019/04/04 06:00 [medline]
PHST- 2018/08/07 00:00 [pmc-release]
AID - bloodadvances.2018017343 [pii]
AID - 2018/017343 [pii]
AID - 10.1182/bloodadvances.2018017343 [doi]
PST - ppublish
SO  - Blood Adv. 2018 Aug 14;2(15):1882-1888. doi: 10.1182/bloodadvances.2018017343.