Upper gastrointestinal acute graft-versus-host disease adds minimal prognostic value in isolation or with other graft-versus-host disease symptoms as currently diagnosed and treated
Sarah Nikiforow,
Tao Wang,
Michael Hemmer,
Stephen Spellman,
Görgün Akpek,
Joseph H. Antin,
Sung Won Choi,
Yoshihiro Inamoto,
Hanna J. Khoury,
Margaret MacMillan,
David I. Marks,
Ken Meehan,
Hideki Nakasone,
Taiga Nishihori,
Richard Olsson,
Sophie Paczesny,
Donna Przepiorka,
Vijay Reddy,
Ran Reshef,
Hélène Schoemans,
Ned Waller,
Daniel Weisdorf,
Baldeep Wirk,
Mary Horowitz,
Amin Alousi,
Daniel Couriel,
Joseph Pidala,
Mukta Arora,
Corey Cutler
Affiliations
Sarah Nikiforow
Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, USA;Harvard Medical School, Boston, MA, USA
Tao Wang
Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI, USA
Michael Hemmer
Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI, USA
Stephen Spellman
CIBMTR, Minneapolis, MN, USA
Görgün Akpek
Rush University Medical Center, Chicago, IL, USA
Joseph H. Antin
Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, USA;Harvard Medical School, Boston, MA, USA
Sung Won Choi
University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA
Yoshihiro Inamoto
National Cancer Hospital, Tokyo, Japan
Hanna J. Khoury
Emory University School of Medicine, Atlanta, GA, USA
Margaret MacMillan
University of Minnesota, Minneapolis, MN, USA
David I. Marks
United Bristol Health Care Trust, UK
Ken Meehan
Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
Hideki Nakasone
Stanford University School of Medicine, CA, USA
Taiga Nishihori
H Lee Moffitt Cancer Center, Tampa, FL, USA
Richard Olsson
Karolinska Institute, Huddinge, Sweden
Sophie Paczesny
Indiana University School of Medicine, Indianapolis, IN, USA
Donna Przepiorka
US Food and Drug Administration, Center for Drug Evaluation and Research, Silver Spring, MD, USA
Vijay Reddy
University of Central Florida College of Medicine, Orlando, FL, USA
Ran Reshef
Columbia University Medical Center, New York, NY, USA
Hélène Schoemans
Katholieke Universiteit, Lueven, Belgium
Ned Waller
Emory University School of Medicine, Atlanta, GA, USA
Daniel Weisdorf
University of Minnesota, Minneapolis, MN, USA
Baldeep Wirk
University of Stony Brook, NY, USA
Mary Horowitz
Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin, Milwaukee, WI, USA
Amin Alousi
MD Anderson Cancer Research Center, Houston, TX, USA
Daniel Couriel
University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA
Joseph Pidala
H Lee Moffitt Cancer Center, Tampa, FL, USA
Mukta Arora
CIBMTR, Minneapolis, MN, USA;University of Minnesota, Minneapolis, MN, USA
Corey Cutler
Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, USA;Harvard Medical School, Boston, MA, USA
Upper gastrointestinal acute graft-versus-host disease is reported in approximately 30% of hematopoietic stem cell transplant recipients developing acute graft-versus-host disease. Currently classified as Grade II in consensus criteria, upper gastrointestinal acute graft-versus-host disease is often treated with systemic immunosuppression. We reviewed the Center for International Blood and Marrow Transplant Research database to assess the prognostic implications of upper gastrointestinal acute graft-versus-host disease in isolation or with other acute graft-versus-host disease manifestations. 8567 adult recipients of myeloablative allogeneic hematopoietic stem cell transplant receiving T-cell replete grafts for acute leukemia, chronic myeloid leukemia or myelodysplastic syndrome between 2000 and 2012 were analyzed. 51% of transplants were from unrelated donors. Reported upper gastrointestinal acute graft-versus-host disease incidence was 12.1%; 2.7% of recipients had isolated upper gastrointestinal acute graft-versus-host disease, of whom 95% received systemic steroids. Patients with isolated upper gastrointestinal involvement had similar survival, disease-free survival, transplant-related mortality, and relapse as patients with Grades 0, I, or II acute graft-versus-host disease. Unrelated donor recipients with isolated upper gastrointestinal acute graft-versus-host disease had less subsequent chronic graft-versus-host disease than those with Grades I or II disease (P=0.016 and P=0.0004, respectively). Upper gastrointestinal involvement added no significant prognostic information when present in addition to other manifestations of Grades I or II acute graft-versus-host disease. If upper gastrointestinal symptoms were reclassified as Grade 0 or I, 425 of 2083 patients (20.4%) with Grade II disease would be downgraded, potentially impacting the interpretation of clinical trial outcomes. Defining upper gastrointestinal acute graft-versus-host disease as a Grade II entity, as it is currently diagnosed and treated, is not strongly supported by this analysis. The general approach to diagnosis, treatment and grading of upper gastrointestinal symptoms and their impact on subsequent acute graft-versus-host disease therapy warrants reevaluation.
