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.

Diagnostic préimplantatoire avec typage HLA : naissance du premier enfant du double espoir en France

“…Depuis, plusieurs équipes dans différents pays ont rapporté leur expérience de diagnostic préimplantatoire couplant la recherche d'une maladie héréditaire à un typage HLA [7][8][9][10][11][12][13].…”

Preimplantation HLA typing for stem cell transplantation treatment of congenital and acquired bone marrow failures

“…This resulted in a clinical pregnancy and birth of a healthy carrier of FANCC gene, whose umbilical cord blood was collected at birth and transplanted to the affected sibling, resulting in a successful hematopoietic reconstitution [2]. This world's first case has opened a new chapter in stem cell transplantation treatment of congenital and acquired diseases using the technology of preimnplantation HLA typing [6][7][8][9][10][11][12][13][14][15]. So the present paper describes the progress in PGD for HLA since the description of the above case, involving preimplantatgion HLA typing for a variety of congenital and acquired conditions, demonstrating that PGD has become an acceptable practical option for HLA matched stem cell transplantation treatment for inherited and sporadic bone marrow failures.…”

Long-term follow-up and factors influencing outcomes after related HLA-identical cord blood transplantation for patients with malignancies: an analysis on behalf of Eurocord-EBMT

“…Whether this was done with the aim of conceiving a "saviour sibling" or simply a reflection of the fact that a significant proportion of parents of a young child with a malignancy may still be planning to expand their family is unknown. Preimplantation genetic diagnosis with HLA-typing has been used to treat patients with nonmalignant inherited disorders, [24][25][26] but, to our knowledge; there is no report of this technique being applied in the setting of a malignant disorder.…”