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

Blood. 2008 Feb 15;111(4):2470-5. doi: 10.1182/blood-2007-09-112987. Epub 2007 Nov 27.


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 (TNFalpha) is an important effector of experimental GVHD, we treated patients with new-onset GVHD with steroids plus the TNFalpha 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 as NCT00141713.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Clinical Trials as Topic
  • Cytokines / blood
  • Drug Therapy, Combination
  • Etanercept
  • Glucocorticoids / therapeutic use*
  • Graft vs Host Disease / drug therapy*
  • Graft vs Host Disease / immunology
  • Hematopoietic Stem Cell Transplantation*
  • Histocompatibility Testing
  • Humans
  • Immunoglobulin G / therapeutic use*
  • Infant
  • Leukemia / therapy
  • Lymphoma / therapy
  • Methylprednisolone / therapeutic use*
  • Middle Aged
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Recombinant Fusion Proteins / therapeutic use*
  • Retrospective Studies
  • Transplantation, Homologous
  • Treatment Outcome


  • Cytokines
  • Glucocorticoids
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Recombinant Fusion Proteins
  • Etanercept
  • Methylprednisolone

Associated data