Bone marrow transplantation for recessive dystrophic epidermolysis bullosa

John E. Wagner, Akemi Ishida-Yamamoto, John A. McGrath, Maria Hordinsky, Douglas R. Keene, Megan J. Riddle, Mark J. Osborn, Troy Lund, Michelle Dolan, Bruce R. Blazar, Jakub Tolar

研究成果: Article同行評審

300 引文 斯高帕斯(Scopus)

摘要

Background: Recessive dystrophic epidermolysis bullosa is an incurable, often fatal mucocutaneous blistering disease caused by mutations in COL7A1, the gene encoding type VII collagen (C7). On the basis of preclinical data showing biochemical correction and prolonged survival in col7-/- mice, we hypothesized that allogeneic marrow contains stem cells capable of ameliorating the manifestations of recessive dystrophic epidermolysis bullosa in humans. Methods: Between October 2007 and August 2009, we treated seven children who had recessive dystrophic epidermolysis bullosa with immunomyeloablative chemotherapy and allogeneic stem-cell transplantation. We assessed C7 expression by means of immunofluorescence staining and used transmission electron microscopy to visualize anchoring fibrils. We measured chimerism by means of competitive polymerase-chain-reaction assay, and documented blister formation and wound healing with the use of digital photography. Results: One patient died of cardiomyopathy before transplantation. Of the remaining six patients, one had severe regimen-related cutaneous toxicity, with all having improved wound healing and a reduction in blister formation between 30 and 130 days after transplantation. We observed increased C7 deposition at the dermal-epidermal junction in five of the six recipients, albeit without normalization of anchoring fibrils. Five recipients were alive 130 to 799 days after transplantation; one died at 183 days as a consequence of graft rejection and infection. The six recipients had substantial proportions of donor cells in the skin, and none had detectable anti-C7 antibodies. Conclusions: Increased C7 deposition and a sustained presence of donor cells were found in the skin of children with recessive dystrophic epidermolysis bullosa after allogeneic bone marrow transplantation. Further studies are needed to assess the long-term risks and benefits of such therapy in patients with this disorder. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00478244.)

原文English
頁(從 - 到)629-639
頁數11
期刊New England Journal of Medicine
363
發行號7
DOIs
出版狀態Published - 2010 8月 12

All Science Journal Classification (ASJC) codes

  • 一般醫學

指紋

深入研究「Bone marrow transplantation for recessive dystrophic epidermolysis bullosa」主題。共同形成了獨特的指紋。

引用此