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Baseline calprotectin fails to predict incidence of acute gastrointestinal graft vs. host disease: a prospective study

Bone Marrow Transplantation volume 54, pages 343–347 (2019)Cite this article

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Allogeneic haematopoietic stem cell transplantation (HSCT) is potentially curative for a wide range of diseases [1]. Despite recent improvements in supportive care, one of the major complication and cause of transplant-related mortality after HSCT is acute and chronic graft-vs-host disease (GvHD) [2, 3]. GvHD occurs as an immunologic reaction of donor T cells against host tissues and has a wide range of clinical manifestations [4]. Overall, 30–50% of patients develop acute GvHD of any grade [3]. Target organs of acute GvHD are generally the skin, the liver and the gastrointestinal tract, and diagnosis relies on clinical and laboratory findings and histological assessments [5]. The degree of HLA-mismatch between patient and donor, is the most important risk factor [6]. Additional factors including minor histocompatibility antigens play a role in the complex pathogenesis of GvHD [7]. Acute GvHD of the gastrointestinal tract results from tissue damage, inflammation triggered by the intestinal microbiota, the activation of the recipient’s immune system and finally of donor T-cells [3]. As the symptoms of gastrointestinal GvHD are not specific, it remains difficult to distinguish them from other causes, mainly toxicity and infections. Therefore, as GvHD prophylaxis and treatment regimens have not changed the clinical course of acute GvHD significantly during the last decades there is a need to predict the individual risk of GvHD and the response to treatment. Furthermore, tailoring GvHD prophylaxis to the individual risk of patients may minimise the risk of GvHD while allowing a Graft-vs. Leukaemia effect. Promising biomarkers have been identified [8, 9]. Additional non-genetic routine laboratory markers that allow estimating the individual risk to develop GvHD based on the current inflammatory status of the patient are urgently needed.

Calprotectin (CPT) is a cytosolic protein of neutrophils, secreted during inflammation. As faecal CPT is increased during inflammation, it is used to identify patients with inflammatory bowel diseases and serves as a biomarker for disease severity [10]. Faecal CPT has been investigated as a diagnostic biomarker at the time of diagnosis of GvHD and as a predictor of steroid response with conflicting results [11,12,13]. Faecal CPT was also investigated as a marker for disease monitoring, showing decreasing levels in patients with cortico-sensitive gastrointestinal GvHD [14]. Preexisting tissue damage and inflammation in target tissues are currently thought to be key amplifiers that correlate with the clinically apparent manifestations of acute GvHD and CPT is a robust marker of gastrointestinal tissue damage. It is conceivable that some preinflammatory state measurable as baseline faecal CPT contributes to GvHD. The aim of the present study was to investigate the role of faecal CPT as a prognostic marker prior to transplantation for the development and severity of acute GvHD.

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Acknowledgements

This study was funded by an unrestricted grant from the Blood Transfusion Service, Swiss Red Cross, Basel, Switzerland.

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  1. These authors contributed equally: Andreas Buser, Christoph Bucher, Andreas Holbro.

Authors and Affiliations

  1. Division of Haematology, University Hospital Basel, Basel, Switzerland

    Nadine Schmidlin, Jakob R. Passweg, Jörg P. Halter, Dominik Heim, Laura Infanti, Alix Stern, Rebekka Plattner, Michael Medinger, Martina Kleber, Andreas Buser, Christoph Bucher & Andreas Holbro

  2. Blood Transfusion Centre, Swiss Red Cross, Basel, Switzerland

    Laura Infanti, Alexandra Plattner, Andreas Buser & Andreas Holbro

  3. Rothen Medical Laboratories, Basel, Switzerland

    Claude Rothen

  4. Translation Project, Roche, Basel, Switzerland

    Christoph Bucher

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Correspondence to Nadine Schmidlin.

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Schmidlin, N., Passweg, J.R., Halter, J.P. et al. Baseline calprotectin fails to predict incidence of acute gastrointestinal graft vs. host disease: a prospective study. Bone Marrow Transplant 54, 343–347 (2019). https://doi.org/10.1038/s41409-018-0292-4

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