Short-term application of doxorubicin chemotherapy immunosuppressive side effects for composite tissue allotransplantation

Background: Adjuvant chemotherapy is often required for the treatment of bone cancers after tumor resection, which often results in a large continuity defect. The immunosuppressive side effects could instead be exploited to allow immediate reconstruction with a composite tissue allograft (CTA) that would provide for replacement of tissues. We used a short course of doxorubicin to achieve a novel method of immunosuppression in a rat model undergoing CTA to create an immunological environment for allograft survival. MATERIALS & Methods: The Institutional Animal Care and Use Committee-approved protocol consisted of 3 experimental groups. Groups 2 and 3 consisted of Brown Norway rats (n = 5) as allograft donors and Lewis rats (n = 5) as transplant recipients. An abdominal wall CTA was harvested off the superficial inferior epigastric vessels. Doxorubicin therapy was administered in group 3 animals. Survival of the CTA was assessed by physical examination and histological analysis. Results: Allotransplant without treatment showed complete clinical and histologic rejection by day 7. Allotransplant rats treated with doxorubicin had clinically and histologically normal grafts through day 10. Kaplan-Meier survival analysis showed a statistically significant difference, with increased CTA survival time to end point with doxorubicin treatment, from a mean of 8.8 days in group 2 to 16.4 days in group 3. Conclusions: Allotransplant flaps without treatment developed complete clinical and histological rejection. The allotransplant group which received doxorubicin showed a delay of allograft rejection with an 86% increased CTA graft survival time. This demonstrates the feasibility of the immunosuppression side effect caused by chemotherapy to prevent rejection of a CTA.