Faculty Collaboration Database

Plasma biomarkers of risk for death in a multicenter phase 3 trial with uniform transplant characteristics post-allogeneic HCT. Blood 2017 Jan 12;129(2):162-170

Date

11/10/2016

Pubmed ID

27827824

Pubmed Central ID

PMC5234220

DOI

10.1182/blood-2016-08-735324

Scopus ID

2-s2.0-85018440780 (requires institutional sign-in at Scopus site)   62 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 = 104, Tac/Mtx = 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 = .0050, P = .0075, respectively) and in a proportional hazards model with time-dependent covariates (adjusted hazard ratio: 2.43 [1.49-3.95], P = .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 = .0069). Low L-Ficolin was associated with hepatic veno-occlusive disease (P = .0053, AUC = 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.

Author List

Abu Zaid M, Wu J, Wu C, Logan BR, Yu J, Cutler C, Antin JH, Paczesny S, Choi SW

Author

Brent R. Logan PhD Director, Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Allografts
Area Under Curve
Biomarkers, Tumor
Drug Therapy, Combination
Enzyme-Linked Immunosorbent Assay
Female
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Immunosuppressive Agents
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Acute
Male
Methotrexate
Middle Aged
Myelodysplastic Syndromes
ROC Curve
Sensitivity and Specificity
Sirolimus
Tacrolimus
Transplantation, Homologous
Young Adult