title: Outcomes of preimplantation genetic diagnosis therapy in treatment of beta-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.
authors.affiliation: Department of Hematology-Oncology, Children's Hospital & Research Center at Oakland, 747 52nd St., 2nd floor, Oakland, CA 94609, USA. nqureshi@mail.cho.org
authors.forename: Naveen
authors.initials: N
authors.lastname: Qureshi
authors.forename: Drucilla
authors.initials: D
authors.lastname: Foote
authors.forename: Mark C
authors.initials: MC
authors.lastname: Walters
authors.forename: Sylvia T
authors.initials: ST
authors.lastname: Singer
authors.forename: Keith
authors.initials: K
authors.lastname: Quirolo
authors.forename: Elliott P
authors.initials: EP
authors.lastname: Vichinsky
mesh_terms: D001757:Blastomeres; D036101:Cord Blood Stem Cell Transplantation; D004624:Embryo Transfer; D005260:Female; D005307:Fertilization in Vitro; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D008297:Male; D011247:Pregnancy; D019836:Preimplantation Diagnosis / Q000191:economics / Q000523:psychology; D012189:Retrospective Studies; D035781:Siblings; D009927:Tissue and Organ Procurement / Q000191:economics / Q000379:methods*; D017086:beta-Thalassemia / Q000175:diagnosis / Q000191:economics / Q000235:genetics / Q000601:surgery*
chemical_list: D006680:HLA Antigens