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Prepublished online as a Blood First Edition Paper on September 22, 2003; DOI 10.1182/blood-2003-02-0587.

Submitted February 25, 2003
Accepted September 11, 2003
Successful hematopoietic stem cell transplantation for Fanconi anemia from an unaffected HLA genotypically-identical sibling selected using preimplantation genetic diagnosis
Satkiran S Grewal, Jeffrey P Kahn, Margaret L MacMillan, Norma K C Ramsay, and John E Wagner*
Department of Pediatric Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN, USA
Center for Bioethics, University of Minnesota, Minneapolis, MN, USA
* Corresponding author; email: wagne002{at}umn.edu.
The only proven cure for Fanconi anemia (FA) associated bone marrow failure is successful allogeneic hematopoietic stem cell transplantation (HSCT). However, HSCT using donors other than HLA-identical siblings are associated with high morbidity and poor survival. We therefore used preimplantation genetic diagnosis (PGD) to select an embryo produced by in vitro fertilization (IVF) that was both unaffected by FA and HLA-identical with the proband. The patient was a 6-year-old female with FA and myelodysplasia previously treated with oxymetholone and prednisone. After 5 cycles of IVF with intrauterine transfer of 7 embryos over a span of 4 years, successful pregnancy ensued. Twenty-eight days after delivery, the patient was transplanted with the donor's HLA-identical umbilical cord blood hematopoietic stem cells (HSCs). Neutrophil recovery occurred on day 17 without subsequent acute or chronic graft-versus-host disease. Currently, 2.5 years after transplant, the patient is well with normal hematopoiesis. In summary, we have described the first successful transplant using HSCs from a donor selected on the basis of specific desirable disease- and HLA-characteristics using IVF and PGD. The medical, legal and ethical issues involved with this approach are discussed.

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