Late acute graft-versus-host disease: a prospective analysis of clinical outcomes and circulating angiogenic factors.
Late acute (LA) graft-versus-host disease (GVHD) is persistent, recurrent, or new-onset acute GVHD symptoms occurring >100 days after allogeneic hematopoietic cell transplantation (HCT). The aim of this analysis is to describe the onset, course, morbidity, and mortality of and examine angiogenic factors associated with LA GVHD. A prospective cohort of patients (n = 909) was enrolled as part of an observational study within the Chronic GVHD Consortium. Eighty-three patients (11%) developed LA GVHD at a median of 160 (interquartile range, 128-204) days after HCT. Although 51 out of 83 (61%) achieved complete or partial response to initial therapy by 28 days, median failure-free survival was only 7.1 months (95% confidence interval, 3.4-19.1 months), and estimated overall survival (OS) at 2 years was 56%. Given recently described alterations of circulating angiogenic factors in classic acute GVHD, we examined whether alterations in such factors could be identified in LA GVHD. We first tested cases (n = 55) and controls (n = 50) from the Chronic GVHD Consortium and then validated the findings in 37 cases from Mount Sinai Acute GVHD International Consortium. Plasma amphiregulin (AREG; an epidermal growth factor [EGF] receptor ligand) was elevated, and an AREG/EGF ratio at or above the median was associated with inferior OS and increased nonrelapse mortality in both cohorts. Elevation of AREG was detected in classic acute GVHD, but not chronic GVHD. These prospective data characterize the clinical course of LA GVHD and demonstrate alterations in angiogenic factors that make LA GVHD biologically distinct from chronic GVHD.
Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN.
Shernan G
SG
Holtan
Mayo Clinic, Phoenix, AZ.
Nandita
N
Khera
Blood and Marrow Transplantation Program, The Icahn School of Medicine at Mount Sinai, New York, NY.
John E
JE
Levine
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
Xiaoyu
X
Chai
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
Barry
B
Storer
Blood and Marrow Transplant Program, Cleveland Clinic, Cleveland, OH.
Hien D
HD
Liu
Stem Cell Transplantation Division, National Cancer Center Hospital, Tokyo, Japan.
Yoshihiro
Y
Inamoto
Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY.
George L
GL
Chen
Department of Medicine, Weill Cornell Medical Center, New York, NY.
Sebastian
S
Mayer
Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN.
Mukta
M
Arora
Mayo Clinic, Phoenix, AZ.
Jeanne
J
Palmer
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
Mary E D
MED
Flowers
Hematologic Malignancies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Corey S
CS
Cutler
Hematologic Malignancies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Alexander
A
Lukez
Division of Blood and Marrow Transplantation, Stanford University Medical Center, Stanford, CA.
Sally
S
Arai
Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN.
Aleksandr
A
Lazaryan
Center for Hematologic Malignancies, Oregon Health and Science University, Portland, OR.
Laura F
LF
Newell
Division of Hematology/Oncology, Stem Cell Transplantation, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
Christa
C
Krupski
Division of Hematology/Oncology, Stem Cell Transplantation, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
Madan H
MH
Jagasia
Medical Oncology, Washington University Medical Center, St. Louis, MO.
Iskra
I
Pusic
Hematology/Oncology, University of North Carolina Healthcare, Chapel Hill, NC.
William
W
Wood
Blood and Marrow Transplantation Program, The Icahn School of Medicine at Mount Sinai, New York, NY.
Anne S
AS
Renteria
Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI.
Gregory
G
Yanik
Blood and Marrow Transplantation Program, Mayo Clinic, Rochester, MN.
William J
WJ
Hogan
Abramson Cancer Center, University of Pennsylvania, Philadelphia PA.
Elizabeth
E
Hexner
Department of Stem Cell Transplantation, University Medical Center, Hamburg-Eppendorf, Germany.
Francis
F
Ayuk
Blood and Marrow Transplantation Program, University of Regensburg, Regensburg, Germany.
Ernst
E
Holler
Blood and Marrow Transplantation Program, Chulalongkorn University, Bangkok, Thailand.
Phandee
P
Watanaboonyongcharoen
Blood and Marrow Transplantation Program, Ohio State University, Columbus, OH; and.
Yvonne A
YA
Efebera
Blood and Marrow Transplantation Program, The Icahn School of Medicine at Mount Sinai, New York, NY.
James L M
JLM
Ferrara
Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN.
Angela
A
Panoskaltsis-Mortari
Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN.
Daniel
D
Weisdorf
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
Stephanie J
SJ
Lee
Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
Joseph
J
Pidala
D000208:Acute Disease; D000328:Adult; D000368:Aged; D043925:Angiogenesis Inducing Agents / Q000097:blood*; D016022:Case-Control Studies; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood* / Q000175:diagnosis / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009017:Morbidity; D011446:Prospective Studies; D016896:Treatment Outcome; D055815:Young Adult
D043925:Angiogenesis Inducing Agents