IMMUNOSUPPRESSION - PRE-CLINICAL AGENTS

K. Dreckmann¹, M. Avsar², A. Knoefel², N. Madrahimov², P. Ziehme², W. Sommer², J. Gottlieb², J. Karstens², A. Haverich³, M. Strueber², G. Warnecke^2
1Department Of Cardiothoracic, Transplantation And Vascular Surgery, Hannover Medical School, Hannover/GERMANY, ², Hannover Medical School, Hannover/GERMANY, ³Heart Transplant Surgery, Medical School Hannover, Hannover/GERMANY

Body: Introduction: Preconditioning of porcine lung transplant recipients with low dose whole body irradiation (WBI) and a donor splenocyte infusion led to the maintenance of peripheral tolerance. In an effort to improve clinical feasibility of the protocol, we wished to substitute WBI with total lymphoid irradiation (TLI), potentially reducing protocol-related toxicity. Methods: Left-sided lung transplantation from MHC mismatched donors was performed in 12 adult minipigs. Non-myeloablative irradiation was administered within 12 hours before transplantation. The animals received a splenocyte infusion on the day of lung transplantation from the lung donor. Intravenous pharmacologic immunosuppression was withdrawn after 28 postoperative days. Allograft survival was monitored by chest radiographs and bronchoscopy. The effect of irradiation was measured via monitoring of differential blood cell counts. Results: Long term transplant survival in the WBI group (n=5) was slightly better than in the TLI group (n=6) which could be explained with a significantly (p=0,01) more efficient depletion of lymphocytes in the WBI group. Protection of the bone marrow from irradiation in the TLI group resulted in positive effects on red cell (p=0,03) and platelet (p=0,01) counts which led to preventing postoperative endobronchial bleeding complications sometimes seen with WBI.. Conclusion: This data shows that total lymphoid irradiation has beneficial effects on peripheral blood cell counts in comparison to a rather unspecific whole body irradiation. Thus the TLI regime offers the possibility to further reduce the toxicity of the treatment, thereby enhancing the feasibility in human lung transplantation. This is, however, potentially at the cost of a reduced success rate of the tolerance induction protocol.

Disclosure: All authors have declared no conflicts of interest.