Faculty Collaboration Database

Galectin-3 predicts acute GvHD and overall mortality post reduced intensity allo-HCT: a BMT-CTN biorepository study. Bone Marrow Transplant 2024 Mar;59(3):334-343

Date

12/19/2023

Pubmed ID

38110620

Pubmed Central ID

PMC10961739

DOI

10.1038/s41409-023-02168-0

Scopus ID

2-s2.0-85180197872 (requires institutional sign-in at Scopus site)

Abstract

Identifying plasma biomarkers early after allo-HCT may become crucial to prevent and treat severe aGvHD. We utilized samples from 203 allo-HCT patients selected from the Blood & Marrow Transplant Clinical Trials Network (BMT CTN) to identify new biomarker models to predict aGvHD and overall mortality. Two new biomarkers (Gal-3 and LAG-3), and previously identified biomarkers (ST2/IL33R, IL6, Reg3A, PD-1, TIM-3, TNFR1) were screened. Increased Gal-3 levels measured at Day +7 post-transplant predicted the development of aGvHD (grade 2-4) in the total population [AUC: 0.602; P = 0.045] while higher Day +14 levels predicted overall mortality due to toxicity among patients receiving reduced intensity conditioning [P = 0.028] but not myeloablative conditioning. Elevated LAG-3 levels (Day +21) were associated with less severe aGvHD [159.1 ng/mL vs 222.0 ng/mL; P = 0.046]. We developed a model utilizing Gal-3, LAG-3, and PD-1 levels at Days +14 and +21 with an improved performance to predict aGvHD and overall non-relapse mortality. We confirmed four informative biomarkers (Reg3A, ST2, TIM-3, and TNFR1) predict severe aGvHD at day +14 and day +21 (grade 3-4). In conclusion, the combination of Gal-3 alone or in combination with LAG-3, and PD-1 is a new informative model to predict aGvHD development and overall non-relapse mortality after allo-HCT.

Author List

McCarthy PL, Attwood KM, Liu X, Chen GL, Minderman H, Alousi A, Bashey A, Lowsky R, Miklos DB, Hansen J, Westervelt P, Yanik G, Waller EK, Howard A, Blazar BR, Wallace PK, Reshef R, Horowitz MM, Maziarz RT, Levine JE, Mohammadpour H

Author

Mary M. Horowitz MD, MS Professor in the Medicine department at Medical College of Wisconsin

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

Biological Specimen Banks
Biomarkers
Galectin 3
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Hepatitis A Virus Cellular Receptor 2
Humans
Interleukin-1 Receptor-Like 1 Protein
Programmed Cell Death 1 Receptor
Receptors, Tumor Necrosis Factor, Type I