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