Autor(es):
Smets, Françoise ; Dobbelaere, Dries ; McKiernan, Patrick ; Dionisi-Vici, Carlo ; Broué, Pierre ; Jacquemin, Emmanuel ; Lopes, Ana Isabel ; Gonçalves, Isabel ; Mandel, Hanna ; Pawlowska, Joanna ; Kamińska, Diana ; Shteyer, Eyal ; Torre, Giuliano ; Shapiro, Riki ; Eyskens, François ; Clapuyt, Philippe ; Gissen, Paul ; Pariente, Danièle ; Grunewald, Stephanie ; Yudkoff, Marc ; Binda, Maria Mercedes ; Najimi, Mustapha ; Belmonte, Nathalie ; de Vos, Beatrice ; Thonnard, Joelle ; Sokal, Etienne
Data: 2019
Identificador Persistente: http://hdl.handle.net/10451/44693
Origem: Repositório da Universidade de Lisboa
Assunto(s): Adolescent; Child; Female; Liver; Urea cycle disorders, inborn; Stem cell transplantation; Infant; Liver regeneration; Treatment outcome; Male; Liver transplantation; Time factors; Humans; Europe; Child, preschool; Age factors; Transplantation, heterologous; Prospective studies; Urea cycle disorders, inborn; Crigler-Najjar syndorme
Descrição
Regenerative medicine using stem cell technology is an emerging field that is currently tested for inborn and acquired liver diseases. Objective. This phase I/II prospective, open label, multicenter, randomized trial aimed primarily at evaluating the safety of Heterologous Human Adult Liver–derived Progenitor Cells (HepaStem) in pediatric patients with urea cycle disorders (UCDs) or Crigler-Najjar (CN) syndrome 6 months posttransplantation. The secondary objective included the assessment of safety up to 12 months postinfusion and of preliminary efficacy. Methods. Fourteen patients with UCDs and 6 with CN syndrome were divided into 3 cohorts by body weight and intraportally infused with 3 doses of HepaStem. Clinical status, portal vein hemodynamics, morphology of the liver, de novo detection of circulating anti– human leukocyte antigen antibodies, and clinically significant adverse events (AEs) and serious adverse events to infusion were evaluated by using an intent-to-treat analysis. Results. The overall safety of HepaStem was confirmed. For the entire study period, patient-month incidence rate was 1.76 for the AEs and 0.21 for the serious adverse events, of which 38% occurred within 1 month postinfusion. There was a trend of higher events in UCD as compared with CN patients. Segmental left portal vein thrombosis occurred in 1 patient and intraluminal local transient thrombus in a second patient. The other AEs were in line with expectations for catheter placement, cell infusion, concomitant medications, age, and underlying diseases. Conclusions. This study led to European clinical trial authorization for a phase II study in a homogeneous patient cohort, with repeated infusions and intermediate doses.
