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.
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.
Goussetis
Evgenios
E
Stem Cell Transplant Unit, Aghia Sofia Children's Hospital, Thivon and Mikras Asias, Athens, Greece. evgoussetis@gmail.com
Konialis
Christopher P
CP
Peristeri
Ioulia
I
Kitra
Vasiliki
V
Dimopoulou
Maria
M
Petropoulou
Theoni
T
Vessalas
George
G
Papassavas
Andreas
A
Tzanoudaki
Marianna
M
Kokkali
Georgia
G
Petrakou
Eftychia
E
Spiropoulos
Antonia
A
Pangalos
Constantinos G
CG
Pantos
Konstantinos
K
Graphakos
Stelios
S
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
D006680:HLA Antigens; D008562:Membrane Glycoproteins; D013481:Superoxides; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D013755:Tetradecanoylphorbol Acetate