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Phase I/II trial of liver–derived mesenchymal stem cells in pediatric liver–based metabolic disorders : a prospective, open label, multicenter, partially randomized, safety study of one cycle of heterologous human adult liver–derived progenitor cells (HepaStem) in urea cycle disorders and Crigler-Najjar syndrome patients

2019Journal article Restricted access
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dc.contributor.authorSmets, Françoise
dc.contributor.authorDobbelaere, Dries
dc.contributor.authorMcKiernan, Patrick
dc.contributor.authorDionisi-Vici, Carlo
dc.contributor.authorBroué, Pierre
dc.contributor.authorJacquemin, Emmanuel
dc.contributor.authorLopes, Ana Isabel
dc.contributor.authorGonçalves, Isabel
dc.contributor.authorMandel, Hanna
dc.contributor.authorPawlowska, Joanna
dc.contributor.authorKamińska, Diana
dc.contributor.authorShteyer, Eyal
dc.contributor.authorTorre, Giuliano
dc.contributor.authorShapiro, Riki
dc.contributor.authorEyskens, François
dc.contributor.authorClapuyt, Philippe
dc.contributor.authorGissen, Paul
dc.contributor.authorPariente, Danièle
dc.contributor.authorGrunewald, Stephanie
dc.contributor.authorYudkoff, Marc
dc.contributor.authorBinda, Maria Mercedes
dc.contributor.authorNajimi, Mustapha
dc.contributor.authorBelmonte, Nathalie
dc.contributor.authorde Vos, Beatrice
dc.contributor.authorThonnard, Joelle
dc.contributor.authorSokal, Etienne
dc.date.accessioned2020-10-28T12:21:14Z
dc.date.available2020-10-28T12:21:14Z
dc.date.issued2019
dc.descriptionCopyright © 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibitedpt_PT
dc.description.abstractRegenerative 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationTransplantation 2019;103:1903–1915pt_PT
dc.identifier.doi10.1097/TP.0000000000002605pt_PT
dc.identifier.eissn1534-6080
dc.identifier.issn0041-1337
dc.identifier.urihttp://hdl.handle.net/10451/44693
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWolters Kluwer Healthpt_PT
dc.relation.publisherversionhttps://journals.lww.com/transplantjournal/pages/default.aspxpt_PT
dc.subjectAdolescentpt_PT
dc.subjectChildpt_PT
dc.subjectFemalept_PT
dc.subjectLiverpt_PT
dc.subjectUrea cycle disorders, inbornpt_PT
dc.subjectStem cell transplantationpt_PT
dc.subjectInfantpt_PT
dc.subjectLiver regenerationpt_PT
dc.subjectTreatment outcomept_PT
dc.subjectMalept_PT
dc.subjectLiver transplantationpt_PT
dc.subjectTime factorspt_PT
dc.subjectHumanspt_PT
dc.subjectEuropept_PT
dc.subjectChild, preschoolpt_PT
dc.subjectAge factorspt_PT
dc.subjectTransplantation, heterologouspt_PT
dc.subjectProspective studiespt_PT
dc.subjectUrea cycle disorders, inbornpt_PT
dc.subjectCrigler-Najjar syndormept_PT
dc.titlePhase I/II trial of liver–derived mesenchymal stem cells in pediatric liver–based metabolic disorders : a prospective, open label, multicenter, partially randomized, safety study of one cycle of heterologous human adult liver–derived progenitor cells (HepaStem) in urea cycle disorders and Crigler-Najjar syndrome patientspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage1915pt_PT
oaire.citation.issue9pt_PT
oaire.citation.startPage1903pt_PT
oaire.citation.titleTransplantationpt_PT
oaire.citation.volume103pt_PT
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT

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