Pilot trial on the use of etanercept and methylprednisolone as primary treatment for acute graft-versus-host disease

Joseph P. Uberti, Lois Ayash, Voravit Ratanatharathorn, Samuel Silver, Christopher Reynolds, Michael Becker, Pavan Reddy, Kenneth R Cooke, Gregory Yanik, Joel Whitfield, Dawn Jones, Raymond Hutchinson, Thomas Braun, James L M Ferrara, John E. Levine

Research output: Contribution to journalArticle

Abstract

Clinical and preclinical data indicate that tumor necrosis factor (TNF)-α is an important mediator of acute graft-versus-host disease (aGVHD) after allogeneic bone marrow transplantation. We completed a study using etanercept, a fusion protein capable of neutralizing TNF-α, for the initial treatment of aGVHD. Etanercept (25 mg subcutaneously) was administered twice weekly for 16 doses, along with methylprednisolone (2 mg/kg) and tacrolimus for biopsy-proven aGVHD. Twenty patients with a median age of 47 years (range, 8-63 years) were enrolled. Fourteen patients with grade II aGVHD (11 family donors and 3 unrelated donors) and 6 patients with grade III aGVHD (3 family donors and 3 unrelated donors) were treated. Twelve patients completed 16 doses of therapy, and 8 received 5 to 15 doses. Reasons for not completing all doses of etanercept included progression of aGVHD (n = 4), relapsed leukemia (n = 2), progression of pulmonary and central nervous system lesions (n = 1), and perforated duodenal ulcer (n = 1). Fifteen (75%) of 20 patients had complete resolution of aGVHD within 4 weeks of therapy. Increasing levels of soluble TNF receptor 1 plasma concentration during the first 4 weeks of therapy indicated progression of aGVHD in 5 patients. In contrast, for 15 responding patients, soluble TNF receptor 1 plasma concentration levels returned to baseline. These data demonstrate the feasibility of using cytokine blockade in the early treatment of aGVHD.

Original languageEnglish (US)
Pages (from-to)680-687
Number of pages8
JournalBiology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
Volume11
Issue number9
DOIs
StatePublished - Sep 2005
Externally publishedYes

Fingerprint

Methylprednisolone
Graft vs Host Disease
Unrelated Donors
Therapeutics
Tumor Necrosis Factor Receptors
Tumor Necrosis Factor-alpha
Tissue Donors
Etanercept
Homologous Transplantation
Tacrolimus
Duodenal Ulcer
Bone Marrow Transplantation
Leukemia
Central Nervous System
Cytokines
Biopsy
Lung

Keywords

  • Acute graft-versus-host disease
  • Etanercept
  • TNF-α

ASJC Scopus subject areas

  • Transplantation

Cite this

Pilot trial on the use of etanercept and methylprednisolone as primary treatment for acute graft-versus-host disease. / Uberti, Joseph P.; Ayash, Lois; Ratanatharathorn, Voravit; Silver, Samuel; Reynolds, Christopher; Becker, Michael; Reddy, Pavan; Cooke, Kenneth R; Yanik, Gregory; Whitfield, Joel; Jones, Dawn; Hutchinson, Raymond; Braun, Thomas; Ferrara, James L M; Levine, John E.

In: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, Vol. 11, No. 9, 09.2005, p. 680-687.

Research output: Contribution to journalArticle

Uberti, JP, Ayash, L, Ratanatharathorn, V, Silver, S, Reynolds, C, Becker, M, Reddy, P, Cooke, KR, Yanik, G, Whitfield, J, Jones, D, Hutchinson, R, Braun, T, Ferrara, JLM & Levine, JE 2005, 'Pilot trial on the use of etanercept and methylprednisolone as primary treatment for acute graft-versus-host disease', Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, vol. 11, no. 9, pp. 680-687. https://doi.org/10.1016/j.bbmt.2005.05.009
Uberti, Joseph P. ; Ayash, Lois ; Ratanatharathorn, Voravit ; Silver, Samuel ; Reynolds, Christopher ; Becker, Michael ; Reddy, Pavan ; Cooke, Kenneth R ; Yanik, Gregory ; Whitfield, Joel ; Jones, Dawn ; Hutchinson, Raymond ; Braun, Thomas ; Ferrara, James L M ; Levine, John E. / Pilot trial on the use of etanercept and methylprednisolone as primary treatment for acute graft-versus-host disease. In: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2005 ; Vol. 11, No. 9. pp. 680-687.
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AU - Ratanatharathorn, Voravit

AU - Silver, Samuel

AU - Reynolds, Christopher

AU - Becker, Michael

AU - Reddy, Pavan

AU - Cooke, Kenneth R

AU - Yanik, Gregory

AU - Whitfield, Joel

AU - Jones, Dawn

AU - Hutchinson, Raymond

AU - Braun, Thomas

AU - Ferrara, James L M

AU - Levine, John E.

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