title: Outcomes of pediatric identical living-donor liver and hematopoietic stem cell transplantation.
abstract: Chronic IS is associated with significant morbidity in transplant recipients. Moreover, IS does not prevent chronic graft failure frequently. Allograft immune tolerance in LT can be induced by complete donor chimerism through allogenic HSCT combined with identical LDLT. This approach may exempt patients from chronic lifelong IS. However, it is unclear whether its benefits justify its risks. Here, we present three cases from our institution and analyze seven additional reports of children treated with HSCT/LDLT, all receiving HSCT due to hemato-oncological indications. In eight of 10 cases, donor macrochimerism resulted in allograft tolerance. Nine patients survived. One patient died due to fulminant ADV infection. Further complications were GvHD (n = 3) and bone marrow failure (n = 2). In conclusion, donor-specific allograft tolerance can be achieved by identical-donor HSCT/LDLT. However, at present, this approach should generally be limited to selected indications due to a potentially unfavorable risk-benefit ratio. Novel toxicity-reduced conditioning protocols for HSCT/LDLT in the absence of malignant or non-hepatic disease may prove to be a sufficiently safe approach for inducing graft tolerance in children receiving a LDLT in the future. This concept may reduce the burden of lifelong IS.
authors.affiliation: Department of Pediatric Gastroenterology and Hepatology, University Hospital Tuebingen, Tuebingen, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Hartleif
authors.affiliation: Department of Pediatric Hematology and Oncology, University Hospital Tuebingen, Tuebingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Lang
authors.affiliation: Department of Pediatric Hematology and Oncology, University Hospital Tuebingen, Tuebingen, Germany.
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.affiliation: Department of Pediatric Hematology and Oncology, University Hospital Tuebingen, Tuebingen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Feuchtinger
authors.affiliation: Department of Pediatric Surgery and Urology, University Hospital Tuebingen, Tuebingen, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Fuchs
authors.affiliation: Department of Visceral- and Transplantation Surgery, University Hospital Tuebingen, Tuebingen, Germany.
authors.forename: Alfred
authors.initials: A
authors.lastname: Königsrainer
authors.affiliation: Department of Visceral- and Transplantation Surgery, University Hospital Tuebingen, Tuebingen, Germany.
authors.forename: Silvio
authors.initials: S
authors.lastname: Nadalin
authors.affiliation: Department of Pediatric Gastroenterology and Hepatology, University Hospital Tuebingen, Tuebingen, Germany. Ekkehard.Sturm@med.uni-tuebingen.de.
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Sturm
mesh_terms: D064591:Allografts; D002675:Child, Preschool; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D018197:Hepatoblastoma / Q000601:surgery; D006801:Humans; D007108:Immune Tolerance; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D008113:Liver Neoplasms / Q000601:surgery; D016031:Liver Transplantation / Q000379:methods*; D019520:Living Donors; D010372:Pediatrics; D011788:Quality of Life; D016511:Severe Combined Immunodeficiency / Q000601:surgery; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents
keywords: chimerism; hematopoietic stem cell transplantation; immunosuppression; living-donor liver transplantation