Preimplantation HLA Typing for Stem Cell Transplantation Treatment of Hemoglobinopathies

Abstract

Preimplantation genetic diagnosis (PGD) for HLA typing is steadily becoming an option for at risk couples with thalassemic children, requiring HLA matched bone marrow transplantation treatment. The paper presents the world's largest PGD experience of 475 cases for over 2 dozens thalassemia mutations, resulting in birth of 132 unaffected children. A total of 146 cases were performed together with preimplantation HLA typing, resulting in detection and transfer of HLA matched unaffected embryos in 83 of them, yielding the birth of 16 HLA matched children, potential donors for their affected siblings. The presented experience of HLA matched stem cell transplantation for thalassemia, following PGD demonstrated a successful hematopoietic reconstitution both for younger and older patients. The data show that PGD is an efficient approach for HLA matched stem cell transplantation treatment for thalassemia.This work is licensed under a Creative Commons Attribution 3.0 License (by-nc 3.0). ©Copyright A.

Preimplantation Hla Typing- Practical Tool for Stem Cell Transplantation Treatment of Congenital and Acquired Disorders

“…With introduction of aneuploidy testing, this may also expand the practical application of preimplantation HLA typing to patients of advanced reproductive age, allowing the improvement of their chances to become pregnant and deliver an HLA matched progeny for stem cell transplantation in the affected siblings. This also makes possible to apply this approach to HLA compatible stem cell transplantation for older affected siblings, which has already been performed in our experience for the 14-years old sibling with thalassemia, resulting in a successful donor cell engraftment with neither acute nor chronic GVHD [34].…”

Evolution and utility of preimplantation genetic testing for monogenic disorders in assisted reproduction - A narrative review

“…The chances of getting a thalassaemia unaffected 100% HLA-matched embryo to an affected sibling were 18.75% and thalassaemia unaffected fully HLA-matched euploid embryo were 9.4%. [ 61 ] Among the numerous disease-linked STRs present, most families have at least two or three informative ones which help provide a diagnosis. [ 62 ]…”

Overview of Preimplantation Genetic Diagnosis (PGD): Historical Perspective and Future Direction

“…Because the majority of patient requesting PGT-HLA are of an advanced reproductive age, PGT-HLA is now increasingly performed concurrently with PGT-A, and it was demonstrated that PGT-M or PGT-H concurrent with PGT-A increases pregnancy rates by 20% or more compared to age-matched cases (<35 years) not concurrently undergoing PGT-A [46]. By the present time, the list of disorders for which PGT-HLA has been applied with successful stem cell transplantation treatment includes thalassaemia, Wiscott-Aldrich syndrome, X-linked hyper IgM syndrome, X-linked hypohidrotic ectodermal dysplasia with immune deficiency and incontinentia pigmenti, and Blackfan-Diamond anemia, with the list continuously expanding [2,[57][58][59][60][62][63][64][65]. The accumulated experience of approximately one thousand cases of PGT-HLA shows that this represents an important prospect for radical treatment of the affected members of the families with congenital and acquired bone marrow failures and immunodeficiencies.…”