New Indications for BMT: Extracellular Matrix Disorder Dystrophic Epidermolysis Bullosa from Jakub Tolar, MD, PhD Blood and Marrow Transplantation University of Minnesota

Collagen Type VII = Anchoring Fibrils Anchoring Fibrils = VELCRO

To determine whether systemically administered hematopietic cells can correct collagen type VII deficiency in recessive dystrophic epidermolysis bullosa.

C7 protein expression adjacent to donor cells in murine model of EB Collagen type VII Donor cell Tolar J, et al. Blood 2009;113:

Clinical Trial CYCLOPHOSPHAMIDE Transplant FLUDARABINE MYCOPHENYLATE CYCLOSPORINE BUSULPHAN Skin Evaluations at days 0, 28, 60, 100, 6 months, 1 and 2 years 1.Photographs of skin and oral mucosa 2.Collagen type VIIimmunofluorescence 3.Electron microscopy (evaluated by blinded reviewers) Days CYCLOPHOSPHAMIDE Transplant FLUDARABINE MYCOPHENYLATE CYCLOSPORINE BUSULPHAN Skin Evaluations at days 0, 28, 60, 100, 6 months, 1 year, and 2 years 1.Photographs of skin and oral mucosa 2.Collagen type VIIimmunofluorescence 3.Electron microscopy (evaluated by blinded reviewers) Days Clinical Trial for RDEB Eligibility 1. Dx of RDEB years 3. Adequate donor 4. Acceptable organ function 5. No SCC

Transplant Improves Skin Blistering Before After BeforeAfter

Transplant Increases Collagen 7 Before After

Non-hematopoietic male donor cells Dermal- epidermal junction Hematopoietic male donor cells Collagen 7 Blood vessel Donor non-hematopoietic cells in epidermis and dermis after HCT

Summary Adoptive transfer of bone marrow and cord blood cells results in functional correction of recessive dystrophic epidermolysis bullosa.

Clinical Trial CYCLOPHOSPHAMIDE Transplant FLUDARABINE MYCOPHENYLATE CYCLOSPORINE BUSULPHAN Skin Evaluations at days 0, 28, 60, 100, 6 months, 1 and 2 years 1.Photographs of skin and oral mucosa 2.Collagen type VIIimmunofluorescence 3.Electron microscopy (evaluated by blinded reviewers) Days CYCLOPHOSPHAMIDE HSC+MSC FLUDARABINE MYCOPHENYLATE CYCLOSPORINE BUSULPHAN Skin Evaluations at days 0, 28, 60, 100, 6 months, 1 year, and 2 years 1.Photographs of skin and oral mucosa 2.Collagen type VIIimmunofluorescence 3.Electron microscopy Days Clinical Trial II for RDEB Eligibility 1. Dx of RDEB years 3. Adequate donor 4. Acceptable organ function 5. No SCC