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HAND/FOREARM TRANSPLANTATION USING A NOVEL CELL-BASED PROTOCOL TO MINIMIZE IMMUNOSUPPRESSION
WP Andrew Lee, MD1, Gerald Brandacher, MD1, Vijay Gorantla, MD, PhD2, Stefan Scneeberger, MD1, Jamie Shores, MD1, Damon Cooney, MD, PhD1, Joseph Imbriglia, MD2, Kodi Azari, MD3, Albert Donnenberg, PhD2, Adriana Zeevi, PhD2, Anthony Demetris, MD2, Diana Metes, MD4, Thomas E. Starzl, MD, PhD4, Joseph E. Losee, MD2.
1Dept. of Plastic and Reconstructive Surgery, Johns Hopkins University, Baltimore, MD, USA, 2University of Pittsburgh, Pittsburgh, PA, USA, 3University of California Los Angeles, Los Angeles, CA, USA, 4Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
Upper extremity transplantation represents a bona fide option for select patients with devastating hand or forearm loss, which could better restore the appearance, anatomy, and function than any other conventional treatment currently available. Despite favorable outcomes, broad clinical application of reconstructive transplantation is limited by the potential side effects of chronic multi-drug immunosuppression. We present our experience with eight hand/forearm transplants performed in five patients under a novel donor bone marrow (BM) cell based immunomodulatory protocol.
Between March 2009 and September 2010 five patients received a bilateral hand (n=2), a bilateral hand/forearm (n=1) or a unilateral (n=2) hand transplant. Patients were treated with alemtuzumab and methylprednisolone for induction followed by tacrolimus monotherapy with target trough levels ranging between 12-15ng/ml during the early post transplant period and 6-10ng/ml thereafter. On pod 14 patients received an unmodified whole donor BM cell infusion isolated from nine vertebral bodies. The case series includes the first American male and female bilateral hand transplants and the world’s first combined total forearm and hand transplant. Comprehensive follow up included functional evaluation, imaging modalities and immunomonitoring.
Hand/forearm allografts are currently maintained on low levels (6-10 ng/ml) of a single immunosuppressive drug in 4 of 5 patients. Acute episodes of skin rejection were infrequent and reversible in all cases. Patients demonstrate sustained improvements in motor function (ROM, intrinsic return, grip and pinch strength) and sensory return correlating with the time after transplantation, level of amputation and participation in hand therapy. 4 of 5 patients are very satisfied with their outcomes so far and are living independently, driving, working, and/or taking vocational training classes with their transplanted hands.
Side effects were few and included transient increase in serum creatinine, hyperglycemia managed with oral hypoglycemics, an episode of hyperuricemia and DVT, and delayed bony union in two cases. No systemic infectious (bacterial or viral) complications occurred. Immunomonitoring revealed transient moderate levels of donor specific antibodies, adequate immunocompetence and no peripheral blood chimerism. Imaging demonstrated patent vessels with no luminal narrowing/occlusion. Protocol skin biopsies showed no or minimal perivascular cellular infiltrates and were negative for C4d.
Our data suggest that this BM cell based immunomodulatory protocol is safe, efficacious, well tolerated, and has allowed for the first time hand/forearm transplantation with low-dose tacrolimus monotherapy. Minimizing immunosuppression could greatly broaden the applicability and indications of reconstructive transplantation.
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