To establish hand transplantation as a safe and effective reconstructive strategy for the
treatment of upper extremity amputations.
To reduce the risk of rejection and enable allograft survival while minimizing the
requirement for long term high dose immunosuppression.
For this purpose, we propose to utilize the "Pittsburgh Protocol", which is an
immunomodulatory strategy that has been implemented in solid organ transplants at UPMC. Early
results in living related liver and kidney patients have confirmed that this protocol
provides the means to allow graft survival with minimization of maintenance immunosuppression
and even allows weaning of some patients from long-term immunosuppression.We hypothesize that
a similar protocol can enable graft survival in highly immunogenic composite tissue
allografts like hand transplants while reducing the number,dosing and/or frequency of
immunosuppressive drugs associated with serious adverse effects.
Suitable candidates will be identified via patient information brochures and via
advertisements directed at upper limb amputees. For this purpose, a web-page will be
constructed for free access by interested individuals. This website will be accessible
through standard search engines. Interested potential subjects will be instructed to contact
the investigator for an appointment. At the time of appointment, candidates will be first
requested to complete a screening consent form (SCF) before undergoing further
evaluation/medical screening procedures. The SCF includes a written consent to obtain PHI of
the candidate. When the candidate visits UPMC he will undergo a consultation with the PI who
will perform a thorough clinical assessment and explain in detail the treatment options,
risks and benefits of the procedure. Candidates will be requested to complete a screening
consent at this stage. Appropriate subjects will then undergo further medical screening
procedures that include a number of examinations and investigations to determine their
candidacy for hand transplantation. Prospective recipients who are selected based on results
of screening procedures will be invited to review and sign the full informed consent form
prior to being wait-listed for the procedure.
The screening tests include:
History and physical exam, including height and weight Urine pregnancy test for all female
subjects of childbearing potential Complete blood count, differential, reticulocyte count,
platelet count ABO type Liver function tests including SGPT or SGOT, serum bilirubin (total
and direct), total protein, albumin, alkaline phosphatase and GGT, PT, PTT with INR Serum
electrolytes and renal function panel to include the following: sodium, potassium, chloride,
carbon dioxide, calcium, phosphorus, magnesium, glucose, creatinine and BUN Urinalysis and
creatinine clearance test to determine GFR Infectious disease studies: HIV antigen, HTLV I-II
antibody, antibodies to HIV 1 and 2, hepatitis C virus, syphilis, hepatitis B core antibody,
and hepatitis B surface antigen titers are required Infectious disease titers: CMV, EBV, HSV,
toxoplasmosis and VZV (IgG and IgM when indicated) Pulmonary function tests, including DLCO2
Chest X-ray EKG and MUGA scan or echocardiogram for determination of cardiac ejection
fraction Sinus X-ray (if clinically indicated) CT scans (CT Angiography)/MRI studies
(Functional MRI, Skeletal MRIs of hand/hips) as indicated by medical history and physical
examination Ophthalmologic examination Dental consult Psychiatric evaluation
Donor Selection Criteria
Brain dead donors who have met the criteria for Determination of Death will be selected by
the hand transplant team in conjunction with the CORE (Center for Organ Recovery and
Education), the organ procurement agency (OPO) for Pittsburgh and covers Pennsylvania, New
York and West Virginia. The mandatory requirements are family consent for limb donation,
stable donor (does not require excessive vasopressors to maintain blood pressure), age
between 18 to 55 years, limb matched for size with recipient, same blood type as recipient,
negative cross-match, and importantly accurately matched for gender, skin tone and race
(may be relative requirement depending on recipient consent).
Recipient Selection Criteria
Recipients will be selected from a population of subjects with upper limb loss. Recipients
may be male or female and of any race, color or ethnicity.
1. Age (>18 years <60 years): Recipients <18 years of age are excluded due to limitations
of giving full informed consent and the potentially increased risk of
lymphoproliferative disorder in a younger population. Once hand transplantation and in
particular the strategy for minimizing immunosuppression has proven to be efficacious
and safe, the restrictions with regard to recipient age may be relaxed.
2. No serious co-existing medical (coronary artery disease, diabetes) or psycho-social
problems (including alcoholism, drug abuse).
3. Must be negative for malignancy (for 10 years) or HIV (at transplant).
4. Negative crossmatch with donor.
5. Negative pregnancy test in female recipient of child bearing potential and consent to
use reliable contraception for at least one year following transplantation.
6. Consent to cell collection, storage, and bone marrow infusion as part of the treatment
7. Amputation may be recent (acute injury) or remote (patient may have undergone
rehabilitation with prostheses).
1. Conditions that may impact the immunomodulatory protocol: These include diseases like
HIV or malignancy that could expose the recipient to an unacceptable risk under
immunosuppressive treatment. Sensitized recipients with high level of preformed
antibodies are also at risk.
2. Conditions that may impact the success of the surgical procedure or increase the risk
of postoperative complications: These include inherited coagulopathies like
Hemophilia, Von-Willebrand's disease, Protein C and S deficiency, Thrombocythemias,
Thallassemias, Sickle Cell disease etc. Mixed connective tissue diseases and collagen
diseases can result in poor wound healing after surgery,
3. Conditions that may impact functional outcomes: Lipopolysaccharidoses and amyloidosis
are few of the conditions that may impact nerve regeneration and impair outcomes.
Also, rare disorders of bone healing like osteopetrosis may also be causes for