Bone marrow transplantation for recessive dystrophic epidermolysis bullosa.
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.)
Wagner
John E
JE
Blood and Marrow Transplant Program, Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA. wagne002@umn.edu
Ishida-Yamamoto
Akemi
A
McGrath
John A
JA
Hordinsky
Maria
M
Keene
Douglas R
DR
Woodley
David T
DT
Chen
Mei
M
Riddle
Megan J
MJ
Osborn
Mark J
MJ
Lund
Troy
T
Dolan
Michelle
M
Blazar
Bruce R
BR
Tolar
Jakub
J
D000293:Adolescent; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D024143:Collagen Type VII / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D016108:Epidermolysis Bullosa Dystrophica / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D005260:Female; D005312:Fetal Blood / Q000637:transplantation*; D005808:Genes, Recessive; D006084:Graft Rejection; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D012155:Reticulin / Q000648:ultrastructure; D012867:Skin / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000009:adverse effects; D014184:Transplantation, Homologous
D024143:Collagen Type VII; D012155:Reticulin
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