577 Successful allogeneic epidermal grafting of chronic recessive dystrophic epidermolysis bullosa wounds from hematopoietic cell donors in the outpatient setting

Abstract

Chronic wounds, or non-healing epidermal erosions present >6 weeks, are common, contribute to morbidity, and lack definitive therapy in recessive dystrophic epidermolysis bullosa (RDEB). The immune tolerance established by allogeneic hematopoietic cell transplantation (HCT) permits adoptive transfer of donor epidermal grafts and establishment of induced mosaicism. In a prospective, open label clinical trial for post-HCT RDEB patients with stable peripheral blood donor chimerism of ≥5%, up to 3 chronic wounds were grafted. Epidermal skin grafts measuring 5 cm2 were obtained from related HCT donors in the outpatient setting using the CelluTomeTM Epidermal Harvesting System. Wound size was measured at baseline, 6, 12, and 52 weeks. Nine patients received a total of 23 epidermal grafts at a median of 1207 days (range 267-3111) post-HCT. The mean (±SD) percent reduction in wound surface area achieved was 61.8% (±31.3), 85.1% (±20.3), and 90.9% (±16.8), at 6, 12, and 52 weeks, respectively, each significantly reduced compared to baseline (p < 0.0001). Donor harvest sites healed quickly with no scarring, though mild hypopigmentation was noted in 5 of 9. Recipient reported benefits include absence of blistering, touch sensation equivalent to native skin, and normal temperature regulation at donor sites. Evaluation of one graft following completion of the study at 1 year revealed wild-type type VII collagen staining by immunofluorescence, normal ultrastructure including intact anchoring fibrils at the dermal-epidermal junction by electron microscopy, and full thickness skin whole DNA donor chimerism of 42% (compared to 16% in concurrently biopsied native skin). Persistence of the donor graft beyond 1 year and observed migration of donor-grafted cells into adjacent wound suggest the epidermal grafts include non-terminally differentiated cells.