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Prediction of graft-versus-host disease: a biomarker panel based on lymphocytes and cytokines

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Abstract

Graft-versus-host disease (GvHD) still belongs to the major challenges after allogeneic hematopoietic stem cell transplantation (HSCT). Immune-suppressive therapy against GvHD is a double-edged sword due to risk of infections and relapse. The ability to adapt prophylactic treatment according to the probability of severe GvHD would be an essential advantage for the patients. We analyzed different biomarkers for their potential to predict the development of GvHD in 28 patients who underwent allogeneic HSCT. Blood was taken once directly after hematopoietic engraftment. In this study, patients were monitored for 12 months after HSCT for the occurrence of acute GvHD or acute/chronic GvHD overlap syndrome. Soluble IL-2 receptor and CD4/CD8 T cell ratio were independently associated with the occurrence of GvHD in the observation period. However, the largest area under the receiver operating characteristic curve with 0.90 was observed when a 5-parameter biomarker score based on CD4+ T cells, CD8+ T cells, CD19− CD21+ precursor B cells, CD4/CD8 T cell ratio, and soluble IL-2 receptor was used to predict GvHD. In addition, CD8+ T cell levels above 2.3% of all mononuclear cells after engraftment may predict relapse-free survival at least for 12 months. In summary, we found a new biomarker panel for prediction of GvHD which is featured by established laboratory assays and high statistical significance. In order to introduce the biomarker panel into routine clinical protocols, we suggest performing a larger multi-center study.

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Authors and Affiliations

  1. Department of Transfusion Medicine, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany

    Holger Budde, Susanne Papert, Jens-Holger Maas, Joachim Riggert & Tobias J. Legler

  2. Institute for Cellular and Molecular Immunology, University Medical Center Göttingen, Humboldtallee 34, 37073, Göttingen, Germany

    Holger M. Reichardt

  3. Department of Hematology and Oncology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany

    Gerald Wulf & Justin Hasenkamp

Authors
  1. Holger Budde
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  2. Susanne Papert
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  3. Jens-Holger Maas
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  4. Holger M. Reichardt
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  5. Gerald Wulf
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  6. Justin Hasenkamp
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  7. Joachim Riggert
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  8. Tobias J. Legler
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Correspondence to Holger Budde.

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The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

This article does not contain any studies with animals performed by any of the authors.

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Informed consent was obtained from all individual participants included in the study.

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Budde, H., Papert, S., Maas, JH. et al. Prediction of graft-versus-host disease: a biomarker panel based on lymphocytes and cytokines. Ann Hematol 96, 1127–1133 (2017). https://doi.org/10.1007/s00277-017-2999-5

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  • DOI: https://doi.org/10.1007/s00277-017-2999-5

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