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

• Published in: Biology of blood and marrow transplantation 2010-03, Vol.16 (3), p.344-349
• Main Authors: Goussetis, Evgenios, Konialis, Christopher P, Peristeri, Ioulia, Kitra, Vasiliki, Dimopoulou, Maria, Petropoulou, Theoni, Vessalas, George, Papassavas, Andreas, Tzanoudaki, Marianna, Kokkali, Georgia, Petrakou, Eftychia, Spiropoulos, Antonia, Pangalos, Constantinos G, Pantos, Konstantinos, Graphakos, Stelios
• Format: Article
• Language: English
• Subjects: Blood Platelets - cytology; Bone Marrow Cells - cytology; Cell Count; Child, Preschool; Embryo, Mammalian - immunology; Female; Fertilization in Vitro; Fetal Blood - cytology; Graft Survival; Granulomatous Disease, Chronic - genetics; Granulomatous Disease, Chronic - therapy; Hematology, Oncology and Palliative Medicine; Hematopoietic stem cell transplantation; Hematopoietic Stem Cell Transplantation - methods; Histocompatibility Testing; HLA Antigens - genetics; HLA Antigens - immunology; Humans; Male; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Mutation, Missense - genetics; NADPH Oxidase 2; NADPH Oxidases - genetics; NADPH Oxidases - metabolism; Neutrophils - cytology; Neutrophils - metabolism; Preimplantation Diagnosis; Preimplantation genetic diagnosis/HLA testing; Respiratory Burst - drug effects; Siblings; Superoxides - metabolism; Tetradecanoylphorbol Acetate - pharmacology; Transplantation Chimera - genetics; Transplantation Chimera - metabolism; Treatment Outcome; X-linked chronic granulomatous disease
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2009.10.010

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.