title: Unrelated CD3/CD19-depleted peripheral stem cell transplantation for Hurler syndrome.
abstract: For patients with mucopolysaccharidosis type IH (MPS1-H; Hurler syndrome), early allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice. One boy and one girl aged 20.5 and 22 months, respectively, with MPS1-H received a conditioning regimen consisting of thiotepa, fludarabine, treosulfan, and ATG. Grafts were peripheral blood stem cells from unrelated donors (10/12 and 11/11 matched), that were manipulated by CD3/CD19 depletion and contained 20.3 and 28.2 × 10(6) CD34+ cells/kg body weight, respectively. Both patients achieved stable hematopoietic engraftment and stable donor chimerism. Neither acute or chronic graft-versus-host disease (GVHD) nor other severe transplant-related complications occurred. At a follow-up of 48 and 37 months, both patients are alive and well with normal levels of α-L-iduronidase and have made major neurodevelopmental progress. Treosulfan-based conditioning offers the advantage of reduced toxicity; the use of unrelated CD3/CD19-depleted peripheral stem cell grafts allows transfusion of high CD34+ cell numbers together with a "tailored" number of CD3+ cells as well as engraftment facilitating cells in order to achieve rapid hematopoietic engraftment while reducing the risk of graft rejection and GVHD. This regimen might be an additional option when unrelated donor HSCT is considered for a patient with MPS1-H.
authors.affiliation: 1Division of Pediatric Hematology/Oncology, University Children's Hospital, Graz, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schwinger
authors.forename: Petra
authors.initials: P
authors.lastname: Sovinz
authors.forename: Martin
authors.initials: M
authors.lastname: Benesch
authors.forename: Herwig
authors.initials: H
authors.lastname: Lackner
authors.forename: Markus
authors.initials: M
authors.lastname: Seidel
authors.forename: Volker
authors.initials: V
authors.lastname: Strenger
authors.forename: Daniela
authors.initials: D
authors.lastname: Sperl
authors.forename: Andrea
authors.initials: A
authors.lastname: Raicht
authors.forename: Michaela
authors.initials: M
authors.lastname: Brunner-Krainz
authors.forename: Eduard
authors.initials: E
authors.lastname: Paschke
authors.forename: Barbara
authors.initials: B
authors.lastname: Plecko
authors.forename: Christian
authors.initials: C
authors.lastname: Urban
mesh_terms: D018941:Antigens, CD19; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D002066:Busulfan / Q000008:administration & dosage / Q000031:analogs & derivatives; D017252:CD3 Complex; D046528:Chimerism; D064420:Drug-Related Side Effects and Adverse Reactions / Q000150:complications; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006086:Graft vs Host Disease; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008212:Lymphocyte Depletion; D008297:Male; D008059:Mucopolysaccharidosis I / Q000150:complications / Q000276:immunology / Q000628:therapy*; D036102:Peripheral Blood Stem Cell Transplantation; D011788:Quality of Life / Q000523:psychology; D016019:Survival Analysis; D013852:Thiotepa / Q000008:administration & dosage; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D018941:Antigens, CD19; D018906:Antineoplastic Agents, Alkylating; D017252:CD3 Complex; D013852:Thiotepa; C018404:treosulfan; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine
keywords: CD3/CD19-depletion; HSCT; Hurler syndrome; hematopoietic stem cell transplantation; mucopolysaccharidosis 1; treosulfan