Gastrointestinal Acute Graft-versus-Host Disease in Children: Histology for Diagnosis, Mesenchymal Stromal Cells for Treatment, and Biomarkers for Prediction of Response

• Published in: Biology of blood and marrow transplantation Vol. 19; no. 11; pp. 1590 - 1599
• Main Authors: Calkoen, Friso G.J, Jol-van der Zijde, Cornelia M, Mearin, M. Luisa, Schweizer, Joachim J, Jansen-Hoogendijk, Anja M, Roelofs, Helene, van Halteren, Astrid G.S, Egeler, R. Maarten, van Tol, Maarten J.D, Ball, Lynne M
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2013
• Subjects: Acute Disease; Acute graft-versus-host disease; Adolescent; Biomarkers; Biomarkers, Tumor - metabolism; Child; Child, Preschool; Children; Female; Gastrointestinal; Gastrointestinal Neoplasms - metabolism; Gastrointestinal Neoplasms - surgery; Gastrointestinal Neoplasms - therapy; Graft vs Host Disease - diagnosis; Graft vs Host Disease - drug therapy; Graft vs Host Disease - etiology; Graft vs Host Disease - therapy; Hematology, Oncology and Palliative Medicine; Hematopoietic Stem Cell Transplantation - adverse effects; Histology; Humans; Infant; Infant, Newborn; Male; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal stromal cells; Mesenchymal Stromal Cells - cytology; Transplantation Conditioning - adverse effects; Transplantation, Autologous; Acute graft-versus-host disease; Mesenchymal stromal cells; Biomarkers; Histology; Children; Gastrointestinal
• DOI: 10.1016/j.bbmt.2013.08.006
• ISSN: 1083-8791

Abstract Steroid-nonresponsive acute graft-versus-host disease (aGVHD) after hematopoietic stem cell transplantation carries a poor prognosis. Various groups have reported beneficial effects of mesenchymal stromal cell (MSC) infusion as salvage treatment. Response to treatment is typically evaluated using the diagnostic clinical criteria for aGVHD. In this study, we evaluated the usefulness of additional gastrointestinal biopsy specimens paired with serum biomarkers. In a cohort of 22 pediatric patients, persistent or recurrent diarrhea was seen in 18 children treated with MSC infusion for steroid-refractory aGVHD. To exclude other causes of gastrointestinal pathology, patients were biopsied for histological analysis. Eight of 12 patients exhibited residual tissue damage and villous atrophy, but no active aGVHD. Serum biomarkers have been identified as an alternative tool for monitoring the response to aGVHD treatment. The value of biomarkers for inflammation, tissue, and endothelial cell damage was evaluated in our cohort. Although predictive of response to treatment and survival, these markers lack the necessary specificity and sensitivity to predict response to MSC therapy. Objective endpoints for clinical trials on the treatment of steroid-refractory aGVHD remain to be defined. Thus, we recommend including biopsies and biomarkers to discriminate between ongoing aGVHD and postinflammatory malabsorption.