|89th Annual Meeting Abstracts
The Pittsburgh Hand Transplant Program - Early Experience with a Novel Immunomodulatory Protocol in Two Patients
W.P. A. Lee, MD, Gerald Brandacher, MD, Stefan Schneeberger, MD, Jaimie T. Shores, MD, Galen S. Wachtman, MD, Jonathan D. Keith, MD, Vijay S. Gorantla, MD, PhD.
University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
PURPOSE: While overall functional outcomes are encouraging among the 38 patients who have received hand transplants in the last decade, the potential morbidity of multiple, high-dose immunosuppressive agents required for graft maintenance limits clinical application of this life-enhancing reconstruction. We present early outcomes with two cases of hand transplantation under a novel cell-based immunomodulatory protocol incorporating donor bone marrow (BM) infusion.
METHODS: Patient #1 was a 24 year old Marine with a wrist level amputation of his right dominant hand secondary to explosion in 2007. He received a unilateral transplant on March 14, 2009. Patient #2 was a 57 year old Veteran with bilateral mid-forearm amputations secondary to Streptococcus Group A sepsis in 1999. He received the first bilateral hand transplant in the US on May 4, 2009. Both patients underwent thorough informed consent after a comprehensive screening evaluation including psychosocial assessment. Leukapheresis was performed at listing and cells cryopreserved. Upon identification of appropriate donors matched for limb size, skin color and gender, patients received Campath 1H (alemtuzumab) induction (30 mg IV) (Day 0). Transplantation was performed (Day 0) and tacrolimus monotherapy (0.2 mg/kg/day) commenced. Donor vertebral body BM cells were processed and cryopreserved (Day 0) and infused on Day 15. Postoperatively, patients underwent rigorous daily hand therapy.
RESULTS: Patient #1 is 8 months (>240 days) after transplant. He has had one episode of clinical acute rejection (POD 43, Banff Grade 2) that completely resolved with topical tacrolimus and clobetasol. Target troughs of tacrolimus have been weaned from 12-15 to 6-8 ng/ml. Serum creatinine levels have ranged between 1.1 and 1.6 mg/dl with 24 hour clearance between 49 - 104 ml/min. Patient #2 is over 6 months (~200 days) after transplant. He has had no episodes of acute rejection to date. Tacrolimus trough levels are weaned to 8-10 ng/ml on low doses (1.5 mg bid). He developed post-transplant hyperglycemia initially requiring insulin but is now managed on oral hypoglycemics with good glycemic control. No systemic steroid or other immunosuppressant has been required in either patient. Results of immunomonitoring reveal insignificant donor specific antibodies (Luminex) and good immunocompetence (Cylex). Both patients have demonstrated sustained improvements in motor function (total active ROM) and sensory return (Semmes-Weinstein testing, temperature and vibratory perception and stereognosis in patient #1, temperature in patient #2). Both patients undergo hand therapy for 3-6 hours 4-5 times per week. Patient #1 has returned to employment as an electrician apprentice.
CONCLUSION: This first report of a novel cell-based immunomodulatory protocol in hand transplantation demonstrates the potential of minimizing the number, dose and duration of drugs used, and in turn improving safety and applicability of this reconstructive modality. Our early data suggest that the protocol is safe, efficacious, and well-tolerated and has allowed graft survival with low dose monotherapy of tacrolimus only. Rejection episodes are low grade and infrequent, with minimal complications. Longer-term follow up will provide greater insight into functional, immunologic and graft survival outcomes.