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.
Tumor necrosis factor-alpha (TNF-alpha) 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-alpha 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.
Department of Pediatrics, University of Michigan Medical School, Ann Arbor, Michigan, USA. ckitko@med.umich.edu
Carrie L
CL
Kitko
Sophie
S
Paczesny
Gregory
G
Yanik
Thomas
T
Braun
Dawn
D
Jones
Joel
J
Whitfield
Sung W
SW
Choi
Raymond J
RJ
Hutchinson
James L M
JL
Ferrara
John E
JE
Levine
D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D006086:Graft vs Host Disease / Q000097:blood*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
D015415:Biomarkers; D047888:Receptors, Tumor Necrosis Factor, Type I