Novel Strategies to Improve Immunomodulation and Non-invasive Clinical Monitoring in VCA

Inclusion Criteria:

For the VCA portion of the study:

- Patients referred due to one or more of these conditions: (1) severe facial deformity
comprising more than 25% of the facial area and/or one or more of the central facial
units (i.e. lip(s), nose, eye(s)), (2) single or bilateral upper limb(s) amputation,
where at least one of the limbs was amputated at the level of the wrist or more
proximal, up to the functional shoulder joint, and (3) severe abdominal wall defect
comprising more than 50% of the functional abdominal wall.

- Injuries must have taken place no more than 15 years and no less than 6 months prior
to presentation for consideration.

- All other conventional reconstruction approaches will have been either exhausted, or
ruled out due to poor prognosis of outcomes.

- Patients will need to possess strong motivation and a willingness to commit to
post-transplant rehabilitation.

- Normal renal and hepatic function within acceptable medical parameters

For the recombinant IL-2 phase of the study:

- At least 3 months have elapsed since the VCA transplant operation

- At least 4 weeks on stable immune suppression and steriods (<5 mg QD).

- No addition or subtraction of other immunosuppressive medications for 4 weeks prior to
enrollment. The dose of immunosuppressive medicines may be adjusted based on the
therapeutic range for that drug.

- Medical evaluations, clinical and laboratory assessments must deem that participants
have adequate organ function.

- The effects of some of the study drugs on the developing human fetus are unknown, or
toxic. For this reason, women of child-bearing potential and men must agree to use
adequate contraception (hormonal or barrier method of birth control; abstinence prior
to study entry and for the duration of study participation). Should a women become
pregnant or suspect she is pregnant while participating in this study, she should
inform her treating physician immediately.

- Subjects must be able to understand and willing to sign a written informed consent
document.

- Skin biopsies from the transplanted parts must show no evidence of rejection for at
least 3 months prior to study enrollment.

Exclusion Criteria:

For the VCA portion of the study:

- History of poor compliance with prostheses or rehabilitation

- Impaired renal, cardiac and/or pulmonary function

- Compromised ability to understand the risk and benefits of participation in the study

- Active malignancy

- Single non-dominant upper limb amputation and no other vascularized composite tissue
injuries justifying VCA

For the IL-2 portion of the study:

- Active infection

- Non-healing wounds

- Pregnancy, because of the potential for teratoenic or abortifacient effects. There is
an unknown but potential risk of adverse events in nursing infants secondary to
treatment of the mother, therefore breastfeeding should be discontinued.

- Rejection episodes within the past 3 months

- Concurrent use of calcineurin-inhibitor plus sirolimus

- New immunosuppressive medication in the 4 weeks prior

- Post-transplant exposure to T-cell or IL-2 targeted medication (e.g. ATG, alemtuzumab,
basiliximab, denileukin diftitox) within 100 days prior.

- Active malignant relapse

- Donor lymphocyte infusion within 100 days prior

- Inability to comply with IL-2 treatment regime

- HIV-positive individuals because of the potential for lethal infections.

- Other investigational drugs within 4 weeks prior to enrollment, unless cleared by the
principal investigator.