The primary study objective is to evaluate local response to split-thickness skin grafts from a matched bone marrow donor to chronic GVHD-affected skin in a hematopoietic stem cell transplant patient.
While the mechanisms are still under active study, GVHD is thought to be a donor T-cell mediated attack that preferentially targets three organs: skin, intestine, and liver. T lymphocytes from the donor identify the patient's organ tissues as foreign and initiate inflammation, leading to end organ damage. The investigator's traditional approach has been to use immune suppressing drugs to dampen this inflammatory response after transplantation. However, this approach is ultimately ineffective for a significant percentage of patients. Therefore, the primary objective of this proposal is to test a novel non-immunosuppressive approach to treatment of cutaneous GVHD using allogeneic skin grafting in an effort to tolerize the engrafted immune system to skin it previously recognized as foreign. The potential benefit to transplant patients is tremendous, including reduced immunosuppression, improved quality of life and lower mortality. A potential novel approach is to apply split-thickness skin grafts from the bone marrow donor to the affected patient's skin. There are four existing case reports that have shown positive outcomes in wound healing in chronic GVHD-associated ulcers. In all four cases, skin grafts were harvested from the patient's allogeneic HLA-matched sibling donors and placed over non-healing wounds (2-5). One case described global improvement in affected skin distant from the site of skin graft application, allowing for tapering of immunosuppressive medications. This suggests potential induction of tolerance by immune cells within the donated skin.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
DEVICE_FEASIBILITY
Masking
NONE
split-thickness skin grafts from a matched bone marrow donor using the CelluTome® Epidermal Harvesting System
University of Minnesota
Minneapolis, Minnesota, United States
Change in CGAA
Evaluation of clinical improvement in inflammation and sclerosis based on visual inspection and photodocumentation with outcome outcomes determined using the Chronic GVHD Activity Assessment (CGAA) to measure therapeutic response. The CGAA is an 8-item assessment measuring symptom severity of GVHD on a scale from 0 (not present) to 10 (as bad as you can imagine). Global score is calculated by summing items.
Time frame: Change from baseline up to 12 months
Change in ELISA Markers of GVHD
Chronic GVHD lesions will be assessed following transplantation through serum ELISA assays of elafin and CXCL10 (validated biomarkers for assessment of GVHD disease activity)
Time frame: Change from baseline up to 12 months
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