Ablative Fractional Laser for Sclerotic GVHD-Associated Joint Contractures

Study Overview
=================
Brief Summary
-----------------
Graft versus host disease (GVHD) is a common complication of allogeneic stem cell transplant.Chronic GVHD is characterized by skin thickening and tightening. Advanced sclerosis can lead to reduced range of motion and incapacitating joint contractures. Once present, there are few therapeutic options. We will treat sclerosis and limb contractures with an ablative fractional laser, a device FDA-approved for scar treatment. This approach has successfully treated contracturesdue to burn scars.

Official Title
-----------------
Ablative Fractional Laser Resurfacing for the Treatment of Scars and Contractures Caused by Sclerotic Skin Changes Chronic Graft Versus Host Disease

Conditions
-----------------
Subjects With Severe, Refractory Sclerotic Skin Changes

Intervention / Treatment
-----------------
* Device: CO2 Laser
* Radiation: Ultrasound
* Diagnostic Test: Skin Biopsy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects must be able to give informed consent All adult patients (18 years of age or older) Severe sclerotic skin changes of chronic graft versus host disease meeting a score of 3 on the NIH consensus criteria for organ scoring of chronic GVHD, a score defined by deep sclerotic features with hidebound skin which cannot be pinched together, resulting in impaired motion. According to the NIH criteria, the patient need not have widespread cutaneous GVHD; hidebound skin OR impaired mobility receive a score of 3 (highest score). Demonstrable range of motion limitations and joint contractures due to sclerotic GVHD across a specific joint / limb amenable to laser therapy must be present. - - Patients must note an inability to bend the joint (e.g. foot, wrist, elbow) freely which compromises the ability to perform specific tasks (e.g. walking up or down stairs, grabbing / making a fist, lifting or raising thearms over the head). As these functional limitations are by their nature subjective (and NIH scoring criteria are themselves subjective) determination of eligibility will be made by the investigator. ECOG Performance Status shall be 0-3 Exclusion Criteria: Persons unable to provide informed consent Pregnant or nursing women, or children under age 18 Active infections such as herpes simplex virus (HSV) Acute, untreated medical problems such as poorly-controlled diabetes, decompensated heart failure, etc. There are no specific contraindications to use of the laser based on skin pigmentation, sun sensitivity, history of keloids, use of specific medications, etc. Appropriateness for trial entry will be determined on an individual basis by the study investigators. Patients with ECOG Performance Status 3 will be excluded. Patients with ANC 1500,PLT 50, or Hgb 8.0 will be excluded.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rAblative Fractional Laser for Sclerotic GVHD-Associated Joint<br>Range of motion limitations and joint contractures due to sclerotic GVHD across a specific joint / limb | Device: CO2 Laser<br>* Perform ablative fractional resurfacing using a 10,600nm carbon dioxide (CO2) laser targeted to thickened, sclerotic plaques causing range of motion limitation and contracture across joints.<br>Radiation: Ultrasound<br>* Patients will undergo ultrasound of the planned treatment site to measure skin thickness and blood flow via Doppler ultrasound.<br>Diagnostic Test: Skin Biopsy<br>* standard 4mm punch biopsy of the skin at the planned treatment site for histologic assessment of skin thickness and sclerosis.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Who Show Improvement in Range of Motion, Flexion, and Extension | Range of motion (flexion, extension, supination, pronation) of the target joint (measured in degrees, using a goniometer). | 5 months from time point zero / baseline | 
| Number of Subjects With Evidence of Collagen Remodeling (Increased Dermal Echogenicity) Compared to Baseline | Measurement of skin echogencity (brightness) in comparison with pre-therapy images of the same areas using high-resolution ultrasound. | 3 months after final laser session (5 months after time zero / baseline) | 
| Number of Subjects Who Show Decrease in Skin Thickness and Sclerosis With Collagen Remodeling as Measured by Before and After Skin Biopsies Biopsy | Trichcrome stain, collagen fiber number and thickness, Herovici stain, elastic fiber length, and dermal thickness. | baseline and 3 months after final laser session |