Originally published as JCO Early Release 10.1200/JCO.2008.17.6545 on November 3 2008

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Risk Factors for Acute Graft-Versus-Host Disease After Human Leukocyte Antigen–Identical Sibling Transplants for Adults With Leukemia

Theresa Hahn, Philip L. McCarthy, Jr, Mei-Jie Zhang, Dan Wang, Mukta Arora, Haydar Frangoul, Robert Peter Gale, Gregory A. Hale, John Horan, Luis Isola, Richard T. Maziarz, Jon J. van Rood, Vikas Gupta, Joerg Halter, Vijay Reddy, Pierre Tiberghien, Mark Litzow, Claudio Anasetti, Stephen Pavletic, Olle Ringdén

From the Roswell Park Cancer Institute, Buffalo, NY; Medical College of Wisconsin, Milwaukee, WI; University of Minnesota, Minneapolis; Mayo Clinic, Rochester, MN; Vanderbilt University, Nashville; St Jude Children's Research Hospital, Memphis, TN; Emory University, Atlanta, GA; Mount Sinai Medical Center, New York, NY; Oregon Health & Science University, Portland, OR; Leiden University Medical Center, Leiden, the Netherlands; Princess Margaret Hospital, Toronto, Ontario, Canada; University Hospital Basel, Basel, Switzerland; Florida Hospital Cancer Institute, Orlando; Moffitt Cancer Center, Tampa, FL; Université de Franche-Comté, Besançon, France; National Cancer Institute, Bethesda, MD; and Karolinska University Hospital, Stockholm, Sweden

Corresponding author: Theresa Hahn, PhD, Department of Medicine, Roswell Park Cancer Institute, Elm & Carlton Sts, Buffalo, NY 14263; e-mail: Theresa.hahn{at}roswellpark.org

Purpose Acute graft-versus-host disease (GVHD) causes substantial morbidity and mortality after human leukocyte antigen (HLA)-identical sibling transplants. No large registry studies of acute GVHD risk factors have been reported in two decades. Risk factors may have changed in this interval as transplant-related techniques have evolved.

Patients and Methods Acute GVHD risk factors were analyzed in 1,960 adults after HLA-identical sibling myeloablative transplant for acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or chronic myeloid leukemia (CML) reported by 226 centers worldwide to the Center for International Blood and Marrow Transplant Research from 1995 to 2002. Outcome was measured as time from transplant to onset of grade 2 to 4 acute GVHD, with death without acute GVHD as a competing risk.

Results Cumulative incidence of grade 2 to 4 acute GVHD was 35% (95% CI, 33% to 37%). In multivariable analyses, factors significantly associated with grade 2 to 4 acute GVHD were cyclophosphamide + total-body irradiation versus busulfan + cyclophosphamide (relative risk [RR] = 1.4; P < .0001), blood cell versus bone marrow grafts in patients age 18 to 39 years (RR = 1.43; P = .0023), recipient age 40 and older versus age 18 to 39 years receiving bone marrow grafts (RR = 1.44; P = .0005), CML versus AML/ALL (RR = 1.35; P = .0003), white/Black versus Asian/Hispanic race (RR = 1.54; P = .0003), Karnofsky performance score less than 90 versus 90 to 100 (RR = 1.27; P = .014), and recipient/donor cytomegalovirus-seronegative versus either positive (RR = 1.20; P = .04). Stratification by disease showed the same significant predictors of grade 2 to 4 acute GVHD for CML; however, KPS and cytomegalovirus serostatus were not significant predictors for AML/ALL.

Conclusion This analysis confirmed several previously reported risk factors for grade 2 to 4 acute GVHD. However, several new factors were identified whereas others are no longer significant. These new data may facilitate individualized risk estimates and raise several interesting biologic questions.

published online ahead of print at www.jco.org on November 3, 2008.

Support information appears in the Acknowledgment. American Society for Blood and Marrow Transplantation provided research support to T.H.

The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, or any other agency of the US Government. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the Office of Naval Research or the National Marrow Donor Program.

T.H. and P.L.M. contributed equally to this work.

Presented in part at the 49th Annual Meeting of the American Society of Hematology, December 8-11, 2007, Atlanta, GA.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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