New Indications for BMT: Extracellular Matrix Disorder Dystrophic Epidermolysis Bullosa from Jakub Tolar, MD, PhD Blood and Marrow Transplantation University of Minnesota
New Indications for BMT: Extracellular Matrix Disorder Dystrophic Epidermolysis Bullosa from Jakub Tolar, MD, PhD Blood and Marrow Transplantation University.
Dec 17, 2015
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New Indications for BMT: Extracellular Matrix Disorder
Dystrophic Epidermolysis Bullosa
from Jakub Tolar, MD, PhD
Blood and Marrow TransplantationUniversity of Minnesota
Collagen Type VII = Anchoring Fibrils
Anchoring Fibrils = VELCRO
To determine whethersystemically 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 cellTolar J, et al.
Blood 2009;113:1167-74
Clinical Trial.
-9 -8 -7 -6 -5 -4 -3 -2 -1 0
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 VII immunofluorescence
3.Electron microscopy (evaluated by blinded reviewers)
Days-9 -8 -7 -6 -5 -4 -3 -2 -1 0
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 VII immunofluorescence
3.Electron microscopy (evaluated by blinded reviewers)
Days
Clinical Trial for RDEBEligibility1. Dx of RDEB2. 0-25 years3. Adequate donor4. Acceptable organ function5. No SCC
Transplant Improves Skin Blistering
Before
After
Before After
Transplant Increases Collagen 7Before
After
Non-hematopoietic male donor cells
Dermal-epidermal junction
Hematopoietic male donor cells
Collagen 7
Blood vessel
Donor non-hematopoietic cellsin 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.
-9 -8 -7 -6 -5 -4 -3 -2 -1 0
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 VII immunofluorescence
3.Electron microscopy (evaluated by blinded reviewers)
Days-9 -8 -7 -6 -5 -4 -3 -2 -1 0
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 VII immunofluorescence
3.Electron microscopy
Days
Clinical Trial II for RDEBEligibility1. Dx of RDEB2. 0-25 years3. Adequate donor4. Acceptable organ function5. No SCC
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