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Blood, 1 February 2004, Vol. 103, No. 3, pp. 1147-1151.
Prepublished online as a Blood First Edition Paper on September 22, 2003; DOI 10.1182/blood-2003-02-0587.
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TRANSPLANTATION
Successful hematopoietic stem cell transplantation for Fanconi anemia from an unaffected HLA-genotype–identical sibling selected using preimplantation genetic diagnosis
Satkiran S. Grewal,
Jeffrey P. Kahn,
Margaret L. MacMillan,
Norma K. C. Ramsay, and
John E. Wagner
From the Department of Blood and Marrow Transplantation and the Center for Bioethics, University of Minnesota, Minneapolis.
The only proven cure for Fanconi anemia (FA)-associated bone marrow failure is successful allogeneic hematopoietic stem cell transplantation (HSCT). However, HSCT with donors other than HLA-identical siblings is associated with high morbidity and poor survival. Therefore, we used preimplantation genetic diagnosis (PGD) to select an embryo produced by in vitro fertilization (IVF) that was unaffected by FA and was HLA-identical to the proband. The patient was a 6-year-old girl with FA and myelodysplasia previously treated with oxymetholone and prednisone. After her parents underwent 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 underwent transplantation with her newborn sibling 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 transplantation, the patient is well and hematopoiesis is normal. In summary, we have described the first successful transplantation, using IVF and PGD, of HSCs from a donor selected on the basis of specific, desirable disease and HLA characteristics. The medical, legal, and ethical issues involved with this approach are discussed. (Blood. 2004;103:1147-1151)
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