TY - JOUR
T1 - Galectin-3 predicts acute GvHD and overall mortality post reduced intensity allo-HCT
T2 - a BMT-CTN biorepository study
AU - McCarthy, Philip L.
AU - Attwood, Kristopher M.
AU - Liu, Xiaojun
AU - Chen, George L.
AU - Minderman, Hans
AU - Alousi, Amin
AU - Bashey, Asad
AU - Lowsky, Robert
AU - Miklos, David B.
AU - Hansen, John
AU - Westervelt, Peter
AU - Yanik, Gregory
AU - Waller, Edmund K.
AU - Howard, Alan
AU - Blazar, Bruce R.
AU - Wallace, Paul K.
AU - Reshef, Ran
AU - Horowitz, Mary M.
AU - Maziarz, Richard T.
AU - Levine, John E.
AU - Mohammadpour, Hemn
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature Limited 2023.
PY - 2024/3
Y1 - 2024/3
N2 - 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. Graphical abstract: (Figure presented.).
AB - 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. Graphical abstract: (Figure presented.).
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U2 - 10.1038/s41409-023-02168-0
DO - 10.1038/s41409-023-02168-0
M3 - Article
C2 - 38110620
AN - SCOPUS:85180197872
SN - 0268-3369
VL - 59
SP - 334
EP - 343
JO - Bone marrow transplantation
JF - Bone marrow transplantation
IS - 3
ER -