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Graft-Versus-Host Disease

Donor and recipient plasma follistatin levels are associated with acute GvHD in Blood and Marrow Transplant Clinical Trials Network 0402

Bone Marrow Transplantation volume 53, pages 64–68 (2018)Cite this article

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Abstract

Follistatin is an angiogenic factor elevated in the circulation after allogeneic hematopoietic cell transplantation (HCT). Elevations in follistatin plasma concentrations are associated with the onset of and poor survival after acute GvHD (aGvHD). Using data from the Blood and Marrow Transplant Clinical Trials Network 0402 study (n=247), we sought to further quantify the longitudinal associations between plasma follistatin levels in transplant recipients, as well as baseline HCT donor follistatin levels, and allogeneic HCT outcomes. Higher recipient baseline follistatin levels were predictive of development of aGvHD (P=0.04). High donor follistatin levels were also associated with the incidence of aGvHD (P<0.01). Elevated follistatin levels on day 28 were associated with the onset of grade II–IV aGvHD before day 28, higher 1-year non-relapse mortality (NRM) and lower overall survival. In multivariate analyses, individuals with follistatin levels >1088 pg/mL at day 28 had a 4-fold increased risk for NRM (relative risk (RR)=4.3, 95% confidence interval (CI) 1.9–9.9, P<0.01) and a nearly three-fold increased overall risk for mortality (RR=2.8, 95% CI 1.5–5.2, P<0.01). Given the multiple roles of follistatin in tissue inflammation and repair, and the confirmation that this biomarker is predictive of important HCT outcomes, the pathobiology of these relationships need further study.

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Acknowledgements

We acknowledge the BMT CTN 0402 study investigators and participating centers. Support for this study was provided by grant #U10HL069294 to the BMT CTN from the National Heart, Lung and Blood Institute and the National Cancer Institute at the National Institutes of Health, along with contributions from Wyeth Pharmaceuticals Inc. The content is solely the responsibility of the authors and does not necessarily represent the official views of the above-mentioned parties. This ancillary study of plasma samples was supported by grants from the National Marrow Donor Program (SGH and LFN). We thank Michael Ehrhardt of the UMN Cytokine Reference Laboratory for expert technical assistance.

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Authors and Affiliations

  1. Division of Pediatric Hematology/Oncology, University of Minnesota, Minneapolis, MN, USA

    L M Turcotte

  2. Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN, USA

    T E DeFor, M L MacMillan, G M Vercellotti, Ane Slungaard, B R Blazar, D J Weisdorf, A Panoskaltsis-Mortari & S G Holtan

  3. Biostatistics Core, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA

    T E DeFor

  4. Center for Hematologic Malignancies, Oregon Health & Science University, Portland, OR, USA

    L F Newell

  5. Hematologic Malignancy Program, Dana Farber Cancer Institute, Boston, MA, USA

    C S Cutler & J H Antin

  6. Pediatric BMT and Cell Therapy, University of Colorado Anschutz Medical Campus and Children’s Hospital, Denver, CO, USA

    M R Verneris

  7. The EMMES Corporation, Rockville, MD, USA

    J Wu

  8. Center for International Blood and Marrow Transplant Research, Minneapolis, MN, USA

    A Howard

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Correspondence to L M Turcotte.

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Turcotte, L., DeFor, T., Newell, L. et al. Donor and recipient plasma follistatin levels are associated with acute GvHD in Blood and Marrow Transplant Clinical Trials Network 0402. Bone Marrow Transplant 53, 64–68 (2018). https://doi.org/10.1038/bmt.2017.236

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