Plasma biomarkers of risk for death in a multicenter phase 3 trial with uniform transplant characteristics post-allogeneic HCT.
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.
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN.|Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN.
Mohammad
M
Abu Zaid
The Emmes Corporation, Rockville, MD.
Juan
J
Wu
The Emmes Corporation, Rockville, MD.
Cindy
C
Wu
Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI.
Brent R
BR
Logan
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN.|Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN.
Jeffrey
J
Yu
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; and.
Corey
C
Cutler
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; and.
Joseph H
JH
Antin
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN.|Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN.
Sophie
S
Paczesny
Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI.
Sung Won
SW
Choi
D000293:Adolescent; D000328:Adult; D064591:Allografts; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood* / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy / Q000401:mortality; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000188:drug therapy / Q000401:mortality; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000188:drug therapy / Q000401:mortality; D012372:ROC Curve; D012680:Sensitivity and Specificity; D020123:Sirolimus / Q000008:administration & dosage; D016559:Tacrolimus / Q000008:administration & dosage; D014184:Transplantation, Homologous; D055815:Young Adult
D014408:Biomarkers, Tumor; D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus; D008727:Methotrexate