Outcomes of Preimplantation Genetic Diagnosis Therapy in Treatment of β‐Thalassemia: A Retrospective Analysis

Abstract

Thalassemia is one of the most common single-gene disorders that can be cured by hematopoietic stem cell transplantation (HCT) from a human leukocyte antigen (HLA)-identical sibling donor. In families that have an affected child, preimplantation genetic diagnosis (PGD) can be used to select an unaffected, HLA-identical embryo. In brief, this procedure requires in vitro fertilization, oocyte retrieval, fertilization, and blastomere biopsy for identification of unaffected HLA-identical embryos. After delivery, umbilical cord blood from the sibling donor is collected for HCT. The objective of this study was to determine the outcomes of families using PGD therapy for cure of beta-thalassemia and to review the limitations of PGD therapy. Families affected with beta-thalassemia who attempted PGD therapy were retrospectively identified and reviewed for indication, attempted cycles, successful pregnancy, and transplantation outcomes. Eight identified families affected by thalassemia underwent PGD. The diagnosis of their affected children included six cases of beta-thalassemia major and two cases of transfusion-dependent hemoglobin E-beta-thalassemia patients. A total of 14 cycles of PGD were attempted, ranging from one to four attempts per family. Following successful identification of HLA-identical cells, two pregnancies occurred, of which one resulted in engraftment of a beta-thalassemia child. PGD therapy offers the possibility of recruiting a suitable donor for HCT, yet is limited by financial cost due to labor-intensive techniques, low probability of obtaining an HLA-matched unaffected embryo, variable implantation capacity, and significant emotional impact. Improvements in PGD therapy's efficacy and cost will make this a more viable option for affected families.

Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease

“…Preimplantation genetic diagnosis of SCD and HLA typing could be useful in this setting. 36 This series confirms and extends previous reports on cerebral vasculopathy. 20,[22][23][24] Early transplantation-related neurologic toxicity has been reported in this setting.…”

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].…”

Hematopoietic cell transplantation for thalassemia and sickle cell disease: past, present and future

“…Reports have confirmed the feasibility of this approach. [45][46][47][48] The financial cost is considerable and serious ethical concerns have been raised by the practice of selecting an embryo solely for the purpose of HSC donation.…”