Recessive dystrophic epidermolysis bullosa ( RDEB ) results from deficiency of type VII collagen ( C7 ), which results in lack of attachment between the epidermis and dermis, severe blistering, and a poor quality of life.
Between 2007 and 2012, 18 individuals ( 0.7–20 years ) with life-threatening, severe generalized recessive dystrophic epidermolysis bullosa have undergone allogeneic hematopoietic cell transplantation at the University of Minnesota.
Of these, 13 were treated with a myeloablative ( MA ) conditioning ( Busulfan, Fludarabine [ FLU ], and Cyclophosphamide [ CY ] ) and 5 were treated with non-MA conditioning ( CY, FLU, anti-thymocyte globulin, and total body irradiation ).
RDEB individuals were transplanted with bone marrow ( BM ) from an HLA-matched sibling ( n=10 ), an HLA-matched unrelated donor ( n=3 ), or a partially matched umbilical cord blood ( UCB, n=5 ).
Importantly, non- myeloablative conditioning was well tolerated with a marked reduction in risk of infection and pulmonary or renal toxicity.
For the entire cohort thus far, the overall probability of survival is 73% with 11 demonstrating partial to marked biochemical and clinical improvement in mucocutaneous disease on the basis of C7 expression, body surface area affected, and resistance to blistering.
Researchers haveconcluded that bone marrow is the preferred graft ( alive and engrafted: 11 of 13 [ 85% ] ) versus umbilical cord blood ( 1 of 5 [ 20% ] ) ( p-value = 0.02 ) and that early results with the non-myeloablative conditioning are promising in terms of toxicity profile and engraftment.
Overall, hematopoietic cell transplantation ( HCT ) has the potential of being a durable, systemic therapy for many people with different forms and severities of epidermolysis bullosa, and sets the stage for using bone marrow cells in the treatment of a broad spectrum of extracellular matrix disorders. ( Xagena )
Tolar J et al, Human Gene Therapy, 2013