Inclusion Criteria:
Participants:
* Competent to provide informed consent, as determined through structured clinical assessment by qualified study personnel, and able to demonstrate adequate psychosocial support, including caregiver or other support-person assistance as needed, to facilitate postoperative recovery, adherence to immunosuppressive therapy, and long-term study follow-up.
where feasible, to support psychosocial and aesthetic integration.
* Willingness to undergo comprehensive psychosocial evaluation and ongoing monitoring by the multidisciplinary team.
* Demonstrated motivation for transplantation and understanding of the investigational nature of upper extremity VCA, including its risks, potential benefits, alternatives, and long-term commitments.
* Evidence of psychological stability and adaptive coping, with attention to prior trauma, grief, and body-image disturbances; stable treatment for conditions such as depression, anxiety, or post-traumatic stress disorder is acceptable when documented and appropriately managed.
* Demonstrated capacity for adherence and, when available, a history of adherence to complex medical regimens, such as chronic disease treatment, dialysis, or transplant care, recognizing that prior barriers may be mitigated through structured supports and longitudinal follow-up.
* Availability of adequate family, caregiver, and/or social support, including an identified caregiver, support person, or formal support services, sufficient to assist with postoperative recovery, medication adherence, transportation, and psychosocial needs. A caregiver/family information sheet will be provided to support persons to promote realistic expectations prior to consent.
* Final psychosocial approval by a transplant mental health professional in consultation with the broader psychosocial team.
* Severe upper extremity disfigurement involving amputation proximal to the wrist.
* Conventional restorative options, including advanced myoelectric or body-powered prostheses, must be documented as exhausted (defined as a minimum of 12 months of consistent use of myoelectric or body-powered prostheses with a QuickDASH score remaining above 30), infeasible (due to stump length or soft tissue coverage), or clinically inadequate for restoring the sensory-motor integration required for the participant's essential functional needs.
* Identified plan for access to immunosuppressive medications and required follow up care (e.g., insurance coverage, assistance programs, institutional support), coordinated with social work and financial counseling.
* Willingness and ability, with available supports, to attend required follow up visits (in person or via approved telehealth where appropriate).
Donor:
* Legal declaration of brain death
* Documented consent for VCA donation.
* ABO and HLA compatibility with the intended recipient.
* Negative crossmatch with the intended recipient (unless protocol specified exceptions are approved by immunology and the IRB).
* EBV and CMV serostatus known (CMV mismatch (donor-positive/recipient-negative (D+/R-) is not automatically exclusionary but managed by the multidisciplinary study team).
* Upper extremity anatomy suitable for transplant (no significant upper extremity trauma, major congenital anomalies, or prior upper extremity surgery that would preclude safe procurement or acceptable aesthetic/functional outcomes).
* Reasonably matched skin tone and sex, where feasible, to support psychosocial and aesthetic integration.
Exclusion Criteria:
* Anatomical or surgical factors that render transplantation unsafe or technically unfeasible (e.g., prohibitive vascular disease, prior surgeries precluding adequate anastomoses) in the judgment of the surgical team.
* Positive Human Immunodeficiency Virus (HIV) serology (unless future evidence and institutional policy support inclusion under tightly controlled conditions).
* Active or inadequately treated serious infection, including tuberculosis, hepatitis B or C with uncontrolled viremia, or syphilis.
* Active malignancy.
* History of melanoma or other high risk, virus driven malignancies.
* Malignancy in remission \<5 years, except for selected low risk, non viral cancers explicitly reviewed and approved by the transplant team.
* Must have clearance for transplant from oncology.
* Decompensated liver disease without hepatology clearance
* Decompensated or advanced cirrhosis
* Uncontrolled or uncorrectable comorbidities that substantially elevate perioperative or immunosuppressive risk despite optimization efforts (e.g., uncontrolled diabetes with end organ damage, uncontrolled hypertension, uncorrected coagulopathy).
* Current pregnancy or stated intent to become pregnant within 12 months of transplant.
* Inability or unwillingness to use effective contraception, when applicable.
* Documented pattern of poor adherence or inability to engage with follow up despite reasonable, trauma informed efforts to reduce barriers (e.g., transportation, scheduling, health literacy, financial support).
* Active psychiatric illness that currently impairs judgment, decisional capacity, or capacity to adhere to care (e.g., untreated psychosis, severe untreated depression with suicidality, impaired reality testing), as determined by the transplant psychosocial team.
* Smoking at the time of transplantation (including cigarettes, vaping, or nicotine products)
* Active substance use disorder (alcohol or drugs) without sustained remission and without adequate recovery supports, unless the multidisciplinary team determines that risk has been sufficiently mitigated.
* Persistent, unrealistic expectations about transplant outcomes that do not resolve despite structured education and counseling.
* Absence of any viable psychosocial or financial support pathway after reasonable efforts to develop one (e.g., no caregiver and no alternative formal support options, or no feasible mechanism to obtain essential medications).
* Inability to provide informed consent, even with appropriate accommodations (e.g., language services, plain language materials, decision aids), and no appropriate legally authorized representative where required.
* Any other condition or circumstance judged by the multidisciplinary transplant team and IRB to pose unacceptable risk or compromise ethical conduct of the study.
Donor:
* Positive serology for HIV, HBV, HCV, TB, or syphilis, or other identified transmissible infections per current OPTN/UNOS and PHS guidance. HTLV testing will be conducted in line with current OPTN standards for donors with potential transmissible infections that are treatable in the recipient.
* Known history of cancer, especially head/neck or hematologic malignancy.
* Permanent upper extremity tattoos or highly identifiable markings judged incompatible with the recipient's preferences or the clinical/ethical judgment of the transplant team.
* History of extremity radiation that compromises tissue viability.
* Public Health Service (PHS) increased risk donors (e.g., recent IV drug use, incarceration) will not be automatically excluded but will require case by case risk assessment, full disclosure to the recipient, and documented multidisciplinary approval.
