title: Gastrointestinal acute graft-versus-host disease in children: histology for diagnosis, mesenchymal stromal cells for treatment, and biomarkers for prediction of response.
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.
authors.affiliation: Immunology, Hematology/Oncology and Hematopoietic Stem Cell Transplantation Section, Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: f.g.j.calkoen@lumc.nl.
authors.forename: Friso G J
authors.initials: FG
authors.lastname: Calkoen
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Jol-van der Zijde
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Mearin
authors.forename: Joachim J
authors.initials: JJ
authors.lastname: Schweizer
authors.forename: Anja M
authors.initials: AM
authors.lastname: Jansen-Hoogendijk
authors.forename: Helene
authors.initials: H
authors.lastname: Roelofs
authors.forename: Astrid G S
authors.initials: AG
authors.lastname: van Halteren
authors.forename: R Maarten
authors.initials: RM
authors.lastname: Egeler
authors.forename: Maarten J D
authors.initials: MJ
authors.lastname: van Tol
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Ball
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D014408:Biomarkers, Tumor / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000378:metabolism / Q000601:surgery / Q000628:therapy*; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000188:drug therapy / Q000209:etiology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D019172:Transplantation Conditioning / Q000009:adverse effects; D014182:Transplantation, Autologous
chemical_list: D014408:Biomarkers, Tumor
keywords: Acute graft-versus-host disease; Biomarkers; Children; Gastrointestinal; Histology; Mesenchymal stromal cells