Transcript Update on New Indications for BMT

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;113:1167-74
Clinical Trial for RDEB
Clinical Trial.
Eligibility
1. Dx of RDEB
2. 0-25 years
3. Adequate donor
4. Acceptable organ function
5. No SCC
Transplant
CYCLOPHOSPHAMIDE
BUSULPHAN
-9
-8
-7
-6
FLUDARABINE
-5
-4
Skin Evaluations at days 0, 28, 60, 100,
-3
-2
-1
0
Days
MYCOPHENYLATE
6 months, 1 year,
and 2 and
years
2 years
1.Photographs of skin and oral mucosa
CYCLOSPORINE
2.Collagen type VII immunofluorescence
3.Electron microscopy (evaluated by blinded reviewers)
Transplant Improves Skin Blistering
Before
After
After
Before
Transplant Increases Collagen 7
Before
After
Non-hematopoietic
male donor cells
Dermalepidermal
junction
Collagen 7
Hematopoietic
male donor
cells
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.
Clinical Trial II for RDEB
Eligibility
1. Dx of RDEB
2. 0-25 years
3. Adequate donor
4. Acceptable organ function
5. No SCC
Transplant
HSC+MSC
CYCLOPHOSPHAMIDE
BUSULPHAN
-9
-8
-7
-6
FLUDARABINE
-5
-4
Skin Evaluations at days 0, 28, 60, 100,
-3
-2
-1
0
Days
MYCOPHENYLATE
6 months, 1 year,
and 2 and
years
2 years
1.Photographs of skin and oral mucosa
CYCLOSPORINE
2.Collagen type VII immunofluorescence
3.Electron microscopy (evaluated by blinded reviewers)