GVHD
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DEVICECelluTome® Epidermal Harvesting System
split-thickness skin grafts from a matched bone marrow donor using the CelluTome® Epidermal Harvesting System
Sponsors
University of Minnesota
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DEVICE_FEASIBILITY
Masking
NONE
Intervention model description
This is an open label, single-institution pilot study 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
- Patient (Recipient) * Subjects will be eligible to participate in the study if all of the following conditions exist: * Diagnosis of chronic, sclerotic, cutaneous graft versus host disease with one or more areas of cutaneous sclerosis and * More than 1 year after HCT with stable hematopoietic engraftment and original transplant donor is available and agrees to be the epidermal donor for this study * Stable (mixed or full) donor hematopoietic engraftment * Original transplant donor is available and willing to be the epidermis donor * Site for skin grafting free of cellulitis or other evidence of infection * Insurance pre-authorization for procedure * Voluntary written consent prior to any research related procedures or treatment. Inclusion Criteria - Donor * Age \> 18 years (based on prior safety testing of the device) * Healthy on physical examination in the opinion of the evaluating physician * Known negativity for Hepatitis B and C, HIV, and HTLV1/2 * Voluntary written consent prior to any research related procedures
Exclusion criteria
Subjects will be excluded from participation in the study if any of the following conditions exist: * Patient with cutaneous infection * Patient with recent change in medical management of chronic cutaneous GVHD (new medication or therapy, or change in dosing of existing medication) within one month of start date.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in CGAA | Change from baseline up to 12 months | 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. |
| Change in ELISA Markers of GVHD | Change from baseline up to 12 months | Chronic GVHD lesions will be assessed following transplantation through serum ELISA assays of elafin and CXCL10 (validated biomarkers for assessment of GVHD disease activity) |
Countries
United States
Outcome results
None listed