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

Abstract

Since we have first introduced preimplantation HLA typing more than 16 years ago, it has become a practical option for stem cell transplantation treatment of congenital and acquired bone marrow failures. This paper summarises our experience of 390 preimplantation HLA typing, representing a part of preimplantation genetic diagnosis (PGD) series, which is the world's largest PGD experience, involving PGD for approximately 500 genetic conditions. The proportion of PGD cases performed combined with HLA typing is steadily increasing, with iimproved awareness of at risk couples regarding PGD as a realistic option for radical treatment of their affected children with bone marrow failures. Preimplantation HLA typing involves detection and transfer of HLA matched unaffecetd embryos, to obtain an HLA compatible offspring as potential donors for their affected siblings. Available results of HLA matched stem cell transplantation treatment following PGD shows a successful hematopoietic reconstitution of patients with different conditions, suggesting that PGD is an efficient approach for HLA matched stem cell transplantation treatment of congetital and acquired bone marrow failures.

Preimplantation genetic testing for inherited immunodeficiency

“…As mentioned, if the couples have already had an affected child with immunodeficiency, PGT with HLA typing makes it also possible to have an access to the HLA identical stem cell transplantation through selection and transfer of those unaffected embryos which are also HLA match to the sibling. A complete cure was observed in our cases after stem cell transplantation in siblings, 10,11 which is in agreement with the results of the other series. 14,15 Although this is still a controversial issue, patients regard this option as the only opportunity to provide their affected children with HLA-matched bone marrow transplantation.…”

“…So PGT is frequently performed together with HLA typing, as HLA matched stem cell transplantation improves significantly the outcome of stem cell transplantation treatment, making PGT an obvious option for inherited forms of immunodeficiency. 10,11 Feasibility of successful use of PGT for immunodeficiency has previously been reported for 36 patients, who produced healthy children free of immunodeficiency. 11 So we present here our experience of 135 PGT cycles performed for 74 at risk patients resulting in birth of 54 unaffected children free of congenital immunodeficiency, which is one of the world's largest experiences.…”

Preimplantation Genetic Testing (PGT) for Human Leukocyte Antigens (HLA) (PGT-HLA)

“…A total of 188 of these cycles also involved PGT-HLA, allowing detecting and transferring unaffected HLA-matched embryos in 103 (54.8%) of them. A total of 159 (1.54 on the average) embryos predicted to be either unaffected carriers or normal and HLA-identical to the affected siblings, which is not significantly different from the expectation [15]. This resulted in 32 unaffected HLA-identical pregnancies and the birth of 32 healthy children.…”

“…Then, it was offered as a primary option to the patients with infertility problems and to those who could not accept the risk for prenatal diagnosis and termination of pregnancy [8][9][10]. This was then followed by PGT-HLA for the couples with existing thalassemia children requiring HLA-compatible bone marrow transplantation [11][12][13][14][15][16]. Again, the objective of PGT in these cases was not only to have a thalassemia-free child but also to ensure that the resulting baby could serve as an HLA-compatible donor for bone marrow transplantation for the affected siblings.…”

“…Again, the objective of PGT in these cases was not only to have a thalassemia-free child but also to ensure that the resulting baby could serve as an HLA-compatible donor for bone marrow transplantation for the affected siblings. Reports of the outcomes of hundreds PGT-HLA cycles demonstrated the practical utility of PGT-M together with testing for the maternal and paternal chromosome 6 identity to the sibling chromosome 6 HLA patterns [11][12][13][14][15][16][17].…”