Post-transplant Range Research Articles

Kinetic of Procalcitonin in the Early Postoperative Course Following Heart Transplantation

It was the aim of the study to determine the kinetics of procalcitonin (PCT) levels following heart transplantation (HTx) and to investigate the prognostic suitability of postoperative changes in PCT levels for patients' outcome. 52 adult heart transplant recipients were divided into two groups according to their in-hospital postoperative outcome retrospectively. Group A (eventful +/- nonsurvivors) of 24 patients (21 males, three females, mean age 54.5 +/- 10.1 years) was compared with Group B (uneventful) of 28 patients (22 males, six females, mean age 53.6 +/- 8.1 years). Serum PCT levels were measured before and daily after operation until day seven. Demographic data, operative data, and clinical endpoints (mortality, infection, severe complication) were analyzed. Mean PCT levels immediately before HTx were <0.3 ng/mL in both groups, respectively. PCT increased with maximum concentrations on the second post-operative day (Group A: 54.6 +/- 44.3 ng/mL; Group B: 9.1 +/- 9.3 ng/mL). After day two the levels decreased to 7.8 +/- 8.8 ng/mL in Group A and 0.6 +/- 0.8 ng/mL in Group B on day seven. Postoperative PCT was increased in nonsurvivors compared to survivors in Group A (81.6 +/- 58.7 ng/mL vs 44.7 +/- 19.8 ng/ml; p < 0.05). PCT levels have been consistently low (<10 ng/mL) in patients with an uneventful course, but more frequently increased in patients with postoperative complications and even associated with an increased mortality early postoperatively when values exceed 80 ng/mL. As a clinical consequence, PCT levels in the first few days following cardiac transplantation can help to identify patients at risk, when concentrations exceed the "normal" posttransplant range.

Long-term acceptance of composite tissue allografts through mixed chimerism and CD28 blockade.

Clinical composite-tissue (hand) transplantation between genetically disparate individuals currently requires potent, nonspecific immunosuppressive agents that are neither completely successful in preventing acute episodes of rejection nor free from complications. The reliance on long-term immunosuppression has prompted this study to achieve donor-specific transplantation tolerance in adult recipients using a nontoxic, nonmyeloablative protocol. Fully mismatched, 4- to 6-week-old ACI (RT1Aa) and Wistar Furth (WF) rats were used as donors and recipients, respectively. Recipients were administered CTLA4-Ig at 2 mg/kg per day (alternate days) in combination with tacrolimus at 1 mg/kg per day (daily) from day 0 through day +10, antilymphocyte serum at 10 mg at day +10 (single dose), and total-body irradiation t 300 cGy (day 0) before bone-marrow transplantation (BMT) (day 0) with 100 x 10(6) T-cell-depleted bone marrow cells. Hindlimb transplants were performed 4 weeks postBMT. Multilineage donor hematopoiesis was determined pre- and posttransplant using flow cytometry. In vitro T-cell responses were evaluated by mixed lymphocyte reactivity assays. CD28 blockade in a transplant model of mixed chimerism effectively aborts T-cell clonal expansion in vitro and in vivo, inhibits the development of acute and chronic rejection of vascularized hindlimb allografts in rats (ACI limbs to ACI-->WF chimeras, n=5; WF limbs to ACI-->WF chimeras, n=4), and subsequently leads to long-term survival of allogeneic skin grafts (n=9). Third-party (F344, n=4) transplants were uniformly rejected within 14 days posttransplant. Multilineage donor hematopoiesis was demonstrated pre- and posttransplant. Donor chimerism, present postBMT, increased throughout the study (pretransplant range 2-28%, mean 17%; posttransplant range 5-49%, mean 34%). Transplant recipients maintained full reactivity to respond to third-party antigens without harmful manifestations of graft-versus-host disease. Although efforts have been made to induce tolerance to composite tissue allografts in adult recipients, thus far, none have succeeded without toxic, myeloablative host preconditioning. Our demonstration that tolerance can be achieved with minimal preconditioning provides a rationale for application to large animals and humans and suggests that although composite tissue allografts may have a significant skin component (and are therefore felt to be highly antigenic), protocols used to induce tolerance to organ transplants may be equally applicable to composite-tissue allotransplantation.