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Galectin-3 predicts acute GvHD and overall mortality post reduced intensity allo-HCT: a BMT-CTN biorepository study

Bone Marrow Transplantation volume 59, pages 334–343 (2024)Cite this article

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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.

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Fig. 1: Plasma levels of Gal-3 in patients with grade 0–1, 2, and 3–4 aGvHD and time to develop aGvHD.
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Acknowledgements

The authors wish to acknowledge the support from Nancy L. DiFronzo, Program Director, Blood Epidemiology and Clinical Therapeutic Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, Amy Foley, Cynthia Vierra-Green and Valerie Stewart, National Marrow Donor Program, Kitty De Jong and Carlos Cedano from Flow Cytometry Shared Resource and Jee Eun Choi from Department of Immunology at Roswell Park. This study was supported by grants from the National Institutes of Health, National Heart Lung Blood Institute (K99 HL155792, R00HL155792 to Hemn. M.), the Roswell Park Alliance, and a donation from Brendan and Elise McCarthy (P.L.M.) and the National Institute of Allergy and Immunology R37 AI34495. Cytometry services were provided by the Flow and Image Cytometry Shared Resource at the Roswell Park Comprehensive Cancer Center which is supported in part by the NCI Cancer Center Support Grant 5P30 CA016056 and NCI R50CA211108 (Hans M.). BMT CTN 1202 biorepository is supported by 5U24CA076518 (NIAIAD, NCI, NHLBI) and U10HL069294 (NHLBI). Support for this study was provided by grants #U10HL069294 and #U24HL138660 to the Blood and Marrow Transplant Clinical Trials Network from the National Heart, Lung, and Blood Institute and the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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Author notes

  1. Deceased: John Hansen.

Authors and Affiliations

  1. Department of Medicine, Transplant and Cellular Therapy Program, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA

    Philip L. McCarthy & George L. Chen

  2. Department of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA

    Kristopher M. Attwood

  3. Flow and Image Cytometry Shared Resource, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA

    Xiaojun Liu, Hans Minderman & Paul K. Wallace

  4. Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX, USA

    George L. Chen & Amin Alousi

  5. Blood and Marrow Transplant Clinical Trials Network GVHD Study Committee, Milwaukee, WI, USA

    George L. Chen & Ran Reshef

  6. Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA, USA

    Asad Bashey

  7. Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA

    Robert Lowsky & David B. Miklos

  8. Clinical Research Division, Fred Hutchinson Cancer Center, University of Washington, Seattle, WA, USA

    John Hansen

  9. Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA

    Peter Westervelt

  10. Blood and Marrow Transplant Program, University of Michigan, Ann Arbor, MI, USA

    Gregory Yanik

  11. Bone Marrow and Stem Cell Transplant Center, Winship Cancer Institute, Emory University, Atlanta, GA, USA

    Edmund K. Waller

  12. National Marrow Donor Program, Minneapolis, MN, USA

    Alan Howard

  13. Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular Therapy, University of Minnesota, Minneapolis, MN, USA

    Bruce R. Blazar

  14. Blood and Marrow Transplantation and Cell Therapy Program, Columbia University Irving Medical Center, New York, NY, USA

    Ran Reshef

  15. Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA

    Mary M. Horowitz

  16. Blood and Marrow Transplant and Cellular Therapy Program, Oregon Health Science University, Portland, OR, USA

    Richard T. Maziarz

  17. The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    John E. Levine

  18. Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA

    Hemn Mohammadpour

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  1. Philip L. McCarthy
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Contributions

Hemn. M. and P.L.M. designed the research, interpreted the data, and wrote the paper; BMT CTN staff supervised the collection and archiving of plasma samples, recorded clinical data; K.M.A served as the statistician responsible for analysis of data; X.L and Hans. M. executed Luminex assays and analyses; G.L.C., P.K.W., B.B., R.R., J.E.L. and R.M. assisted in the analysis of data and writing of the manuscript. A.A, A.B., R.L., D.B.M., P.W., G.Y., E.K.W. provided samples for the study. R.R., J.E.L. and G.L.C. participated in the 1202 adjudication committee. M.M.H. is the P.I. of the BMT CTN which provided the samples. All authors reviewed the manuscript and provided comments and edits.

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Correspondence to Hemn Mohammadpour.

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P.L.M. Advisory Board/Consulting: BlueBird Biotech, Bristol-Myers Squibb, Celgene, Fate Therapeutics, Janssen, Juno, Karyopharm, Magenta Therapeutics, Sanofi, Takeda; Honoraria: BlueBird Biotech, Bristol-Myers Squibb, Celgene, Fate Therapeutics, Janssen, Juno, Karyopharm, Magenta Therapeutics, Sanofi, Takeda.

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McCarthy, P.L., Attwood, K.M., Liu, X. et al. Galectin-3 predicts acute GvHD and overall mortality post reduced intensity allo-HCT: a BMT-CTN biorepository study. Bone Marrow Transplant 59, 334–343 (2024). https://doi.org/10.1038/s41409-023-02168-0

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