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Blood, 15 February 2008, Vol. 111, No. 4, pp. 2470-2475.
Prepublished online as a Blood First Edition Paper on November 27, 2007; DOI 10.1182/blood-2007-09-112987.


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TRANSPLANTATION

Etanercept plus methylprednisolone as initial therapy for acute graft-versus-host disease

John E. Levine1,2, Sophie Paczesny3, Shin Mineishi2, Thomas Braun4, Sung W. Choi1,2, Raymond J. Hutchinson1, Dawn Jones3, Yasser Khaled2, Carrie L. Kitko1,2, Daniel Bickley3, Oleg Krijanovski2, Pavan Reddy2, Gregory Yanik1,2, and James L. M. Ferrara1,2

1 Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI; 2 Department of Medicine, University of Michigan Medical School, Ann Arbor, MI; 3 Blood and Marrow Transplantation Program, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; 4 Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI.

Graft-versus-host disease (GVHD) is a principal cause of morbidity following allogeneic hematopoietic cell transplantation (HCT). Standard therapy for GVHD, high-dose steroids, results in complete responses (CRs) in 35% of patients. Because tumor necrosis factor-{alpha} (TNF{alpha}) is an important effector of experimental GVHD, we treated patients with new-onset GVHD with steroids plus the TNF{alpha} inhibitor etanercept on a previously reported pilot trial (n = 20) and a phase 2 trial (n = 41). We compared their outcomes with those of contemporaneous patients with GVHD (n = 99) whose initial therapy was steroids alone. Groups were similar with respect to age, conditioning, donor, degree of HLA match, and severity of GVHD at onset. Patients treated with etanercept were more likely to achieve CR than were patients treated with steroids alone (69% vs 33%; P < .001). This difference was observed in HCT recipients of both related donors (79% vs 39%; P = .001) and unrelated donors (53% vs 26%; P < .001). Plasma TNFR1 levels, a biomarker for GVHD activity, were elevated at GVHD onset and decreased significantly only in patients with CR. We conclude that etanercept plus steroids as initial therapy for acute GVHD results in a substantial majority of CRs. This trial was referenced at www.clinicaltrials.gov as NCT00141713 [ClinicalTrials.gov] .


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