Plasma biomarkers of risk for death in a multicenter phase 3 trial with uniform transplant characteristics post–allogeneic HCT

Mohammad Abu Zaid, Juan Wu, Cindy Wu, Brent R. Logan, Jeffrey Yu, Corey Cutler, Joseph H. Antin, Sophie Paczesny, Sung Won Choi

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

A phase 3 clinical trial (BMT CTN 0402) comparing tacrolimus/sirolimus (Tac/Sir) vs tacrolimus/methotrexate (Tac/Mtx) as graft-versus-host disease (GVHD) prophylaxis after matched-related allogeneic hematopoietic cell transplantation (HCT) recently showed no difference between study arms in acute GVHD-free survival. Within this setting of a prospective, multicenter study with uniform GVHD prophylaxis, conditioning regimen, and donor source, we explored the correlation of 10 previously identified biomarkers with clinical outcomes after allogeneic HCT. We measured biomarkers from plasma samples collected in 211 patients using enzyme-linked immunosorbent assay (Tac/Sir 5 104, Tac/ Mtx 5 107). High suppression of tumorigenicity-2 (ST2) and T-cell immunoglobulin mucin-3 (TIM3) at day 28 correlated with 2-year nonrelapse mortality in multivariate analysis (P 5 .0050, P 5 .0075, respectively) and in a proportional hazards model with time-dependent covariates (adjusted hazard ratio: 2.43 [1.49–3.95], P 5 .0038 and 4.87 [2.53–9.34], P < .0001, respectively). High ST2 and TIM3 correlated with overall survival. Chemokine (C-X-C motif) ligand 9 (CXCL9) levels above the median were associated with chronic GVHD compared with levels below the median in a time-dependent proportional hazard analysis (P 5 .0069). Low L-Ficolin was associated with hepatic veno-occlusive disease (P 5 .0053, AUC 5 0.80). We confirmed the correlation of plasma-derived proteins, previously assessed in single-center cohorts, with clinical outcomes after allogeneic HCT within this prospective, multicenter study.

Original languageEnglish (US)
Pages (from-to)162-170
Number of pages9
JournalBlood
Volume129
Issue number2
DOIs
StatePublished - Jan 12 2017

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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