title: Improved survival after acute graft-versus-host disease diagnosis in the modern era.
abstract: A cute graft-versus-host disease remains a major threat to a successful outcome after allogeneic hematopoietic cell transplantation. While improvements in treatment and supportive care have occurred, it is unknown whether these advances have resulted in improved outcome specifically among those diagnosed with acute graft-versus-host disease. We examined outcome following diagnosis of grade II-IV acute graft-versus-host disease according to time period, and explored effects according to original graft-versus-host disease prophylaxis regimen and maximum overall grade of acute graft-versus-host disease. Between 1999 and 2012, 2,905 patients with acute myeloid leukemia (56%), acute lymphoblastic leukemia (30%) or myelodysplastic syndromes (14%) received a sibling (24%) or unrelated donor (76%) blood (66%) or marrow (34%) transplant and developed grade II-IV acute graft-versus-host disease (n=497 for 1999-2001, n=962 for 2002-2005, n=1,446 for 2006-2010). The median (range) follow-up was 144 (4-174), 97 (4-147) and 60 (8-99) months for 1999-2001, 2002-2005, and 2006-2010, respectively. Among the cohort with grade II-IV acute graft-versus-host disease, there was a decrease in the proportion of grade III-IV disease over time with 56%, 47%, and 37% for 1999-2001, 2002-2005, and 2006-2012, respectively (P<0.001). Considering the total study population, univariate analysis demonstrated significant improvements in overall survival and treatment-related mortality over time, and deaths from organ failure and infection declined. On multivariate analysis, significant improvements in overall survival (P=0.003) and treatment-related mortality (P=0.008) were only noted among those originally treated with tacrolimus-based graft-versus-host disease prophylaxis, and these effects were most apparent among those with overall grade II acute graft-versus-host disease. In conclusion, survival has improved over time for tacrolimus-treated transplant recipients with acute graft-versus-host disease.
authors.affiliation: Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA.
authors.forename: Hanna J
authors.initials: HJ
authors.lastname: Khoury
authors.affiliation: CIBMTR (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.|Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: CIBMTR (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Hemmer
authors.affiliation: Utah Blood and Marrow Transplant Program-Adults, Salt Lake City, UT, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Couriel
authors.affiliation: Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Amin
authors.initials: A
authors.lastname: Alousi
authors.affiliation: Center for Hematologic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Corey
authors.initials: C
authors.lastname: Cutler
authors.affiliation: Department of Pediatric Hematology Oncology, King Faisal Specialist Hospital Center & Research, Riyadh, Saudi Arabia.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Aljurf
authors.affiliation: Center for Hematologic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Antin
authors.affiliation: Department of Pediatric Hematology Oncology, King Faisal Specialist Hospital Center & Research, Riyadh, Saudi Arabia.
authors.forename: Mouhab
authors.initials: M
authors.lastname: Ayas
authors.affiliation: Hematology Branch, National Heart, Lung and Blood Institute-NIH, Bethesda, MD, USA.
authors.forename: Minoo
authors.initials: M
authors.lastname: Battiwalla
authors.affiliation: Department of Hematology, University Hospital, Grenoble, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Cahn
authors.affiliation: Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Department of Pediatrics, New York Medical College, Valhalla, NY, USA.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Cairo
authors.affiliation: Division of Hematology/Oncology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Yi-Bin
authors.initials: YB
authors.lastname: Chen
authors.affiliation: Hematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College London, UK.
authors.forename: Robert Peter
authors.initials: RP
authors.lastname: Gale
authors.affiliation: Department of Internal Medicine, Mayo Clinic Rochester, MN, USA.|Department of Oncology, King Faisal Specialist Hospital Center & Research, Riyadh, Saudi Arabia.
authors.forename: Shahrukh
authors.initials: S
authors.lastname: Hashmi
authors.affiliation: Division of Pediatric Hematology/Oncology, Department of Pediatrics, Washington University School of Medicine in St. Louis, MO, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hayashi
authors.affiliation: Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Madan
authors.initials: M
authors.lastname: Jagasia
authors.affiliation: Division of Hematology/Oncology/Bone Marrow Transplantation, Department of Medicine, University of Wisconsin Hospital and Clinics, Madison, WI, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Juckett
authors.affiliation: Division of Hematology and Oncology, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Rammurti T
authors.initials: RT
authors.lastname: Kamble
authors.affiliation: Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Kharfan-Dabaja
authors.affiliation: Department of Internal Medicine, Mayo Clinic Rochester, MN, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Litzow
authors.affiliation: Blood & Marrow Transplant Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA.
authors.forename: Navneet
authors.initials: N
authors.lastname: Majhail
authors.affiliation: Division of Hematology and Oncology, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Miller
authors.affiliation: Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: Taiga
authors.initials: T
authors.lastname: Nishihori
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Muna
authors.initials: M
authors.lastname: Qayed
authors.affiliation: University Hospital of Leuven, Belgium.
authors.forename: Helene
authors.initials: H
authors.lastname: Schoemans
authors.affiliation: Department of Hematology, Academische Ziekenhuis, Maastricht, the Netherlands.
authors.forename: Harry C
authors.initials: HC
authors.lastname: Schouten
authors.affiliation: Department of Hematology, Hopital Saint Louis, Paris, France.
authors.forename: Gerard
authors.initials: G
authors.lastname: Socie
authors.affiliation: Department of Medicine, University of Calgary, AB, Canada.
authors.forename: Jan
authors.initials: J
authors.lastname: Storek
authors.affiliation: Isala Clinics Zwolle, the Netherlands.
authors.forename: Leo
authors.initials: L
authors.lastname: Verdonck
authors.affiliation: Division of Hematology and Oncology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Vij
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Wood
authors.affiliation: Division of Hematology/Oncology & HSCT, The Center for Cancer and Blood Disorders, Children's Hospital/Louisiana State University Medical Center, New Orleans, LA, USA.
authors.forename: Lolie
authors.initials: L
authors.lastname: Yu
authors.affiliation: Division of Clinical Hematology, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Martino
authors.affiliation: Thomas Jefferson University Hospital, Philadelphia, PA, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Carabasi
authors.affiliation: Cincinnati Children's Hospital Medical Center, OH, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Dandoy
authors.affiliation: Hematologic Malignancies & Bone Marrow Transplant, Department of Medical Oncology, New York Presbyterian Hospital/Weill Cornell Medical Center, NY, USA.
authors.forename: Usama
authors.initials: U
authors.lastname: Gergis
authors.affiliation: Division of Hematology/Oncology/Bone Marrow Transplantation, Department of Medicine, University of Wisconsin Hospital and Clinics, Madison, WI, USA.
authors.forename: Peiman
authors.initials: P
authors.lastname: Hematti
authors.affiliation: The Blood and Marrow Transplant Group of Georgia, Northside Hospital, Atlanta, GA, USA.
authors.forename: Melham
authors.initials: M
authors.lastname: Solh
authors.affiliation: Department of Medicine, University of Calgary, AB, Canada.
authors.forename: Kareem
authors.initials: K
authors.lastname: Jamani
authors.affiliation: Dana Farber Cancer Institute/Boston Children's Hospital, MA, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Lehmann
authors.affiliation: Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Bipin
authors.initials: B
authors.lastname: Savani
authors.affiliation: Department of Pediatric Hematology, Oncology and Bone Marrow Transplant, British Columbia's Children's Hospital, The University of British Columbia, Vancouver, BC, Canada.
authors.forename: Kirk R
authors.initials: KR
authors.lastname: Schultz
authors.affiliation: Division of Bone Marrow Transplant, Seattle Cancer Care Alliance, WA, USA.
authors.forename: Baldeep M
authors.initials: BM
authors.lastname: Wirk
authors.affiliation: CIBMTR (Center for International Blood and Marrow Transplant Research), National Marrow Donor Program/Be the Match, Minneapolis, MN, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Spellman
authors.affiliation: Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota Medical Center, Minneapolis, MN, USA.
authors.forename: Mukta
authors.initials: M
authors.lastname: Arora
authors.affiliation: Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA joseph.pidala@moffitt.org.
authors.forename: Joseph
authors.initials: J
authors.lastname: Pidala
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D001782:Blood Donors; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007223:Infant; D007951:Leukemia, Myeloid / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009190:Myelodysplastic Syndromes / Q000628:therapy*; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D055815:Young Adult