Plasma Elevations of Tumor Necrosis Factor-Receptor-1 at Day 7 Postallogeneic Transplant Correlate with Graft-versus-Host Disease Severity and Overall Survival in Pediatric Patients

Carrie L. Kitko, Sophie Paczesny, Gregory Yanik, Thomas Braun, Dawn Jones, Joel Whitfield, Sung W. Choi, Raymond J. Hutchinson, James L.M. Ferrara, John E. Levine

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Tumor necrosis factor-α (TNF-α) is known to play a role in the pathogenesis of graft-versus-host disease (GVHD), a cause of significant morbidity and treatment-related mortality (TRM) after allogeneic hematopoietic stem cell transplantation (HCT). We measured the concentration of TNF-Receptor-1 (TNFR1) in the plasma of HCT recipients as a surrogate marker for TNF-α both prior to transplant and at day 7 in 82 children who underwent a myeloablative allogeneic HCT at the University of Michigan between 2000 and 2005. GVHD grade II-IV developed in 39% of patients at a median of 20 days after HCT. Increases in TNFR1 level at day 7 post-HCT, expressed as ratios compared to pretransplant baseline, correlated with the severity of GVHD (P = .02). In addition, day 7 TNFR1 ratios >2.5 baseline were associated with inferior 1-year overall survival (OS 51% versus 74%, P = .04). As an individual biomarker, TNFR1 lacks sufficient precision to be used as a predictor for the development of GVHD. However, increases in the concentration of TNFR1, which are detectable up to 2 weeks in advance of clinical manifestations of GVHD, correlate with survival in pediatric HCT patients.

Original languageEnglish (US)
Pages (from-to)759-765
Number of pages7
JournalBiology of Blood and Marrow Transplantation
Volume14
Issue number7
DOIs
StatePublished - Jul 1 2008

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Keywords

  • GVHD
  • Hematopoietic stem cell transplantation
  • Pediatrics
  • TNF

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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