Background: Millions of people each year sustain injuries, have tumors surgically removed, or
are born with defects that require complex reconstructive surgeries to repair. In the case of
hand, forearm, or arm amputation, prostheses only provide less than optimal motor function
and no sensory feedback. However, hand and arm transplantation is a means to restore the
appearance, anatomy, and function of a native hand. Although over 70 hand transplants have
been performed to date and good functional results have been achieved, widespread clinical
use has been limited due to adverse effects of life-long and high-dose immunosuppression
needed to prevent graft rejection. Risks include infection, cancer, and metabolic problems,
all of which can greatly affect recipients' quality of life, make the procedure riskier, and
jeopardize the potential benefits of hand transplantation.
Study Design: This non-randomized, Phase II clinical trial will document the use of a new
immunomodulatory protocol (aka - Pittsburgh Protocol, Starzl Protocol) for establishing hand
transplantation as a safe and effective reconstructive treatment for upper extremity
amputations by minimizing maintenance immunosuppression therapy in unilateral and bilateral
hand/forearm transplant patients. This protocol combines lymphocyte depletion with donor bone
marrow cell infusion and has enabled graft survival using low doses of a single
immunosuppressive drug followed by weaning of treatment. Initially designed for
living-related solid organ donation, this regimen has been adapted for use with grafts
donated by deceased donors. The investigators propose to perform 30 human hand transplants
employing this novel protocol.
Specific Aims: 1) To establish hand transplantation as a safe and effective reconstructive
strategy for the treatment of upper extremity amputations; 2) To reduce the risk of rejection
and enable allograft survival while minimizing the requirement for long-term high dose
multi-drug immunosuppression.
Significance of Research: Hand transplantation could help upper extremity amputees recover
functionality, self-esteem, and the capability to reintegrate into family and social life as
"whole" individuals. The protocol offers the potential for minimizing the morbidity of
maintenance immunosuppression, thereby beneficially shifting the risk/benefit ratio of this
life-enhancing procedure and enabling widespread clinical application of hand
transplantation.
Phase:
Phase 2
Details
Lead Sponsor:
Johns Hopkins University
Collaborators:
Armed Forces Institute of Regenerative Medicine U.S. Army Medical Research Acquisition Activity