title: Ferritin as an early marker of graft rejection after allogeneic hematopoietic stem cell transplantation in pediatric patients.
abstract: Diagnosis of adverse events following hematopoietic stem cell transplantation (HSCT) is mainly assigned to clinical symptoms or biopsies and thus rather unspecific and/or invasive. Studies indicate a distinct role of serum ferritin in HSCT and its correlation with adverse events such as graft-versus-host disease (GvHD), veno-occlusive disease (VOD), or infections. However, published data on the relevance of ferritin as a prognostic marker for post-transplant adverse events is rare, especially in pediatric patients. The present study analyzes ferritin plasma concentrations of 138 pediatric patients after HSCT between 2007 and 2010 including the control group (n = 21). Given the initial results regarding ferritin as a significant predictor for acute graft rejection after allogeneic HSCT in 9 of the 138 pediatric patients, serum ferritin of all pediatric patients (n = 27) who experienced graft rejection between 2007 and 2014 was analyzed. In addition, laboratory parameters including C-reactive protein (CRP), lactate dehydrogenase (LDH), fibrinogen, and D-dimer as possible differentiation markers for graft rejection were determined. In 24 (88.9 %) of the 27 pediatric patients with graft rejection, a significant increase of ferritin levels was observed 1 to 7 days prior to (P < 0.0001) and at the time of graft rejection (P < 0.0001). Moreover, there was an increase of D-dimer, CRP, LDH, and fibrinogen 1-7 days before graft rejection. Ferritin increased significantly at time of VOD (P = 0.0067), at time of intestinal (P < 0.0001) and skin GvHD (P < 0.0001), and at time of sepsis (P = 0.0005) and bacteremia (P = 0.0029). Ferritin might serve as a readily available identification marker for differentiation and identification of adverse events after HSCT in combination with other laboratory markers.
authors.affiliation: Department I - General Paediatrics, Hematology/Oncology, Children's Hospital, University Hospital Tuebingen, Hoppe-Seyler-Str. 1, 72076, Tuebingen, Germany. michaela.doering@med.uni-tuebingen.de.|Dr. von Hauner'sches Kinderspital, Pediatric Hematology, Oncology and Stem Cell Transplantation, Ludwig-Maximilians-University München, Lindwurmstrasse 4, 80337, Munich, Germany. michaela.doering@med.uni-tuebingen.de.
authors.forename: Michaela
authors.initials: M
authors.lastname: Döring
authors.affiliation: Department I - General Paediatrics, Hematology/Oncology, Children's Hospital, University Hospital Tuebingen, Hoppe-Seyler-Str. 1, 72076, Tuebingen, Germany. karin.cabanillas@med.uni-tuebingen.de.
authors.forename: Karin Melanie
authors.initials: KM
authors.lastname: Cabanillas Stanchi
authors.affiliation: Department I - General Paediatrics, Hematology/Oncology, Children's Hospital, University Hospital Tuebingen, Hoppe-Seyler-Str. 1, 72076, Tuebingen, Germany. judith.feucht@med.uni-tuebingen.de.
authors.forename: Judith
authors.initials: J
authors.lastname: Feucht
authors.affiliation: Department I - General Paediatrics, Hematology/Oncology, Children's Hospital, University Hospital Tuebingen, Hoppe-Seyler-Str. 1, 72076, Tuebingen, Germany. manon.queudeville@med.uni-tuebingen.de.
authors.forename: Manon
authors.initials: M
authors.lastname: Queudeville
authors.affiliation: Department I - General Paediatrics, Hematology/Oncology, Children's Hospital, University Hospital Tuebingen, Hoppe-Seyler-Str. 1, 72076, Tuebingen, Germany. heiko-manuel.teltschik@med.uni-tuebingen.de.
authors.forename: Heiko-Manuel
authors.initials: HM
authors.lastname: Teltschik
authors.affiliation: Department I - General Paediatrics, Hematology/Oncology, Children's Hospital, University Hospital Tuebingen, Hoppe-Seyler-Str. 1, 72076, Tuebingen, Germany. peter.lang@med.uni-tuebingen.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Lang
authors.affiliation: Department I - General Paediatrics, Hematology/Oncology, Children's Hospital, University Hospital Tuebingen, Hoppe-Seyler-Str. 1, 72076, Tuebingen, Germany. tobias.feuchtinger@med.uni-muenchen.de.|Dr. von Hauner'sches Kinderspital, Pediatric Hematology, Oncology and Stem Cell Transplantation, Ludwig-Maximilians-University München, Lindwurmstrasse 4, 80337, Munich, Germany. tobias.feuchtinger@med.uni-muenchen.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Feuchtinger
authors.affiliation: Department I - General Paediatrics, Hematology/Oncology, Children's Hospital, University Hospital Tuebingen, Hoppe-Seyler-Str. 1, 72076, Tuebingen, Germany. rupert.handgretinger@med.uni-tuebingen.de.
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.affiliation: Department of Paediatric Hematology and Oncology, University Hospital Hamburg-Eppendorf, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany. i.mueller@uke.de.
authors.forename: Ingo
authors.initials: I
authors.lastname: Müller
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D005293:Ferritins / Q000097:blood*; D006084:Graft Rejection / Q000097:blood* / Q000175:diagnosis* / Q000209:etiology; D019337:Hematologic Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000639:trends*; D006801:Humans; D007223:Infant; D008297:Male; D012189:Retrospective Studies; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000639:trends; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000639:trends
chemical_list: D015415:Biomarkers; D005293:Ferritins
keywords: Allogeneic stem cell transplantation; Ferritin; Graft-versus-host disease; Infection; Pediatric patients; Veno-occlusive disease