immunology-2018-posters-abstracts

Immunology 2018

J u l y 0 5 - 0 7 , 2 0 1 8

V i e n n a , A u s t r i a

Page 112

Journal of Clinical Immunology and Allergy

ISSN 2471-304X

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t h

I n t e r n a t i o n a l C o n f e r e n c e o n

Immunology

ransplant paradigm has shifted from immuno-suppression to immuno-modulation, which aims to balance the host and graft

responses against each other and achieve co-existence without high-dose, multi-drug immunosuppression. Following the

new paradigm, our team developed an experimental protocol first in a rat then swine hind-limb transplant model, utilizing donor

bone marrow cells infusion into transplant recipients as a way to facilitate clonal exhaustion and deletion mechanisms and thus

modulate the host immune responses towards graft acceptance. We showed that, following an induction protocol of lymphoid

depletion and donor bone marrow infusion, the immunosuppression requirement for limb transplant in our swine model was

reduced to a single agent of Tacrolimus. Furthermore, the dosage of Tacrolimus may be weaned over time to very low trough

levels without jeopardizing the limb allograft. We also showed in the laboratory the feasibility of local, targeted treatment of

allograft rejection by topical application of steroid or Tacrolimus to the skin component, thus obviating the need for increased

systemic immunosuppression for treatment of mild tomoderate rejection episodes of limb allografts. These experimental findings

provided the foundation for a clinical immuno-modulatory protocol for VCA that permits allograft survival with minimum, single-

agent (monotherapy) immunosuppression. In our clinical protocol, Campath1-H, an anti-CD52 monoclonal antibody, was used

for lymphoid depletion just prior to transplant. Donor marrow was obtained by removing the lower thoracic and lumbar vertebral

bodies (with donor family permission), from which marrow cells were extracted in a GMP laboratory. A high dose of unmodified

donor marrow cells, numbering over a billion, were then prepared into a suspension and infused intravenously into the hand

allograft recipient 2 weeks after transplant. All patients were maintained on Tacrolimus monotherapy with its blood trough levels

reduced from 12-15 ng/ml initially after transplant to 4-6 ng/ml typically after one to two years. Our hand transplant recipients

have not experienced any long term metabolic, infectious, or neoplastic complications. Our team has performed transplantation

of 11 hands/arms in 7 patients since 2009, including 4 bilateral transplants, at Johns Hopkins and University of Pittsburgh.

Surgical complications were readily treated without long-term consequences, including bleeding, delayed wound healing, bony

nonunion and deep venous thrombosis. Each recipient has been maintained on our immuno-modulatory protocol of low-dose

Tacrolimus monotherapy without apparent adverse effects of immunosuppression. Good to excellent functions were achieved

in all but one recipient, restoring functional independence and personal autonomy and allowing returning to work or school.

The functional recovery in the three patients with trans-humeral transplantation has been notable in the restoration of wrist and

digital flexion and extension from re-innervation of donor forearm musculature. In one transplant recipient whose biceps and

triceps were replaced with those from the donor, near-normal range of active elbow motion was obtained. For the majority of our

recipients, therefore, hand transplantation transformed their lives as they became independent and productive

Immono-modulatory protocol for hand and arm

transplantation

W P Andrew Lee, Jaimie T Shores and Gerald Brandacher

Johns Hopkins University, USA

Insights Allergy Asthma Bronchitis 2018, Volume: 4

DOI: 10.21767/2471-304X-C1-003