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Figure 7. Nearly three-year follow-up of the world’s first overseas hand-forearm transplantation

nonconstructive manner. The limbs are photographed, carefully dressed, and splinted. The patient then
recovers in the Intensive Care Unit for close monitoring.

Immunosuppressive protocol
The immunologic profile of hand transplants differs slightly when compared with solid organ transplants
[88]
due to their composite tissue, including bone, tendon, nerve, muscle, and skin, which is more antigenic .
[96]
That being said, the immunosuppressive therapy is modeled after solid organ transplantation . This
includes induction therapy of several perioperative doses of polyclonal/monoclonal antibodies such as
thymoglobulin along with IV steroids. Maintenance therapy consists of a multidrug regimen of tacrolimus
[16]
(calicineurin inhibitor), mycophenolate mofetil, and prednisone . Alterations to this standard in an
attempt to reduce acute rejection episodes have been investigated and applied, including steroid withdrawal,
conversion to mammalian target of rapamycin (mTOR) inhibitor sirolimus from tacrolimus, the use of
topical steroids, and Belatacept (selective T-cell costimulation blocker) [79,97-100] . Switching tacrolimus to
[99]
sirolimus has been done because of increased creatinine values, resulting in normalization of levels .
Immunomodulation strategies to create a state of immunologic chimerism in the recipient, such as infusion
of donor-derived bone marrow stem cells as part of induction therapy, have been shown to be safe, well-
[101]
tolerated, and allow for low-dose tacrolimus monotherapy . Furthermore, delivery of rapamycin has been
shown to promote immunoregulation and survival of the VCA [102] .

Consequences of prolonged immunosuppression include opportunistic infections, and medication
side effects such as metabolic disorders, nephrotoxicity, neurotoxicity, avascular necrosis, and wound
healing issues related to steroid use and neoplasms (e.g., cutaneous and lymphoproliferative disorders).
The future of hand transplantation will depend on minimizing side effects of immunosuppression,
or perhaps even more ambitious, achieving donor-specific immunologic tolerance and rejection-free
maintenance without the use of immunosuppression. Prophylaxis therapy includes antibiotics for 10 days,
trimethoprim/sulfamethaxoazole to prevent Pneumocystis carinii pneumonia, and valganciclovir to prevent
[99]
cytomegalovirus infection/reactivation for six months .
Postoperative course
Standardized vigilant follow-up is paramount to monitor for signs of surgical complications, acute/chronic
rejection, and untoward effects of immunosuppression. This becomes even more critical with the growing
transatlantic cases, which require follow-up with a treatment team with expertise in VCA in the area of
residence in addition to follow-up with the team that performed and is familiar with the transplant. At six