title: Successful hematopoietic stem cell transplantation in 2 children with X-linked chronic granulomatous disease from their unaffected HLA-identical siblings selected using preimplantation genetic diagnosis combined with HLA typing.
abstract: We report 2 children with X-linked chronic granulomatous disease (X-CGD) who underwent hematopoietic stem cell transplantation (HSCT) using grafts from their siblings selected before implantation to be both unaffected and HLA-matched donors. Preimplantation genetic diagnosis (PGD) along with HLA-typing were performed on preimplantation embryos by single-cell multiplex polymerase chain reaction using informative short tandem repeat markers in the HLA locus together with the gene region containing the mutations. Two singleton pregnancies resulted from the intrauterine transfer of selected embryos; these developed to term, producing 1 healthy female and 1 X-CGD carrier female, which are HLA-identical siblings to the 2 affected children. Combined grafts of umbilical cord blood (UCB) and bone marrow (BM) stem cells were administered to the recipients after myeloablative (MA) conditioning at the ages of 4.5 years and 4 years, respectively. Both patients are well, with complete donor hematopoietic and immunologic reconstitution, at 18 and 13 months posttransplantation, respectively. This report demonstrates that HSCT with HLA-matched sibling donors created by PGD/HLA typing of in vitro fertilized embryos is a realistic therapeutic option and should be presented as such to families with children who require a non-urgent HSCT but lack an HLA-genoidentical donor.
authors.affiliation: Stem Cell Transplant Unit, Aghia Sofia Children's Hospital, Thivon and Mikras Asias, Athens, Greece. evgoussetis@gmail.com
authors.forename: Evgenios
authors.initials: E
authors.lastname: Goussetis
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Konialis
authors.forename: Ioulia
authors.initials: I
authors.lastname: Peristeri
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Kitra
authors.forename: Maria
authors.initials: M
authors.lastname: Dimopoulou
authors.forename: Theoni
authors.initials: T
authors.lastname: Petropoulou
authors.forename: George
authors.initials: G
authors.lastname: Vessalas
authors.forename: Andreas
authors.initials: A
authors.lastname: Papassavas
authors.forename: Marianna
authors.initials: M
authors.lastname: Tzanoudaki
authors.forename: Georgia
authors.initials: G
authors.lastname: Kokkali
authors.forename: Eftychia
authors.initials: E
authors.lastname: Petrakou
authors.forename: Antonia
authors.initials: A
authors.lastname: Spiropoulos
authors.forename: Constantinos G
authors.initials: CG
authors.lastname: Pangalos
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Pantos
authors.forename: Stelios
authors.initials: S
authors.lastname: Graphakos
mesh_terms: D001792:Blood Platelets / Q000166:cytology; D001854:Bone Marrow Cells / Q000166:cytology; D002452:Cell Count; D002675:Child, Preschool; D004622:Embryo, Mammalian / Q000276:immunology; D005260:Female; D005307:Fertilization in Vitro; D005312:Fetal Blood / Q000166:cytology; D006085:Graft Survival; D006105:Granulomatous Disease, Chronic / Q000235:genetics / Q000628:therapy*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense / Q000235:genetics; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D019836:Preimplantation Diagnosis; D016897:Respiratory Burst / Q000187:drug effects; D035781:Siblings; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018183:Transplantation Chimera / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens; D008562:Membrane Glycoproteins; D013481:Superoxides; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D013755:Tetradecanoylphorbol Acetate