DACLIZUMAB (ZENAPAX) IS EFFECTIVE IN PREVENTION OF ACUTE REJECTION IN LIVER TRANSPLANTATION ONLY IN COMBINATION WITH CALCINEURIN INHIBITORS. (1999)

88 Daclizumab is a humanized monoclonal antibody directed against the ∝ chain of the IL-2 receptor. Previous studies have demonstrated its efficacy in preventing rejection in renal transplantation. Its efficacy has been associated with a paucity of adverse effects, including a lack of neuro- and nephrotoxicity. Currently, we have reviewed our experience with the use of daclizumab in liver transplant recipients. Thirty-two patients were given daclizumab as induction therapy in the setting of hepatic transplantation. Seven of these patients were enrolled in a prospective, IRB approved pilot study to determine the efficacy of induction with daclizumab in conjunction with corticosteroids and mycophenolate mofetil (MMF) WITHOUT the use of calcineurin inhibitors (C.I.). These patients were given two perioperative doses of daclizumab (1 mg/kg in the operating room and 1 mg/kg on postoperative day 1). The recipients were also given MMF 1500 mg po bid, and methylprednisolone. The other twenty-five patients had various indications for daclizumab including preexisting renal insufficiency (n=17), a desire to avoid MMF (n=3), neurologic conditions (n=2), and others (n=3). The period of follow up ranged from 1 to 12 months. Results: The prospective pilot study was halted after the first seven patients were enrolled because of an unacceptably high rate of rejection (7/7=100%). Of note, in this study, a significant proportion had severe steroid resistant rejection (4/7=57%), with two patients not responding to OKT3. Three patients also had a histologic finding of centrilobular necrosis, vascular or antibody mediated rejection. After their rejection episodes, these patients were all eventually started on a calcineurin inhibitor. In this study, the C.I. was given at a mean of 36 days postop. One patient died with recurrent hepatitis C and chronic rejection, and another has been relisted for transplant because of chronic rejection. Of note, the daclizumab levels and saturation of IL-2 receptors on peripheral blood lymphocytes were suboptimal in these patients. Overall, 16/32 patients (50%) had at least one biopsy proven episode of rejection. Interestingly, in five of these cases of rejection (31%), centrilobular ballooning and necrosis was seen. Excluding the seven pilot study patients that originally did not receive calcineurin inhibitor, 9/25 (36%) had at least one episode of rejection. In the recipients that suffered from rejection (n=16), the mean number of days postoperatively that calcineurin inhibitor was given was 23 days. In the recipients (n=16) that did not suffer from rejection, calcineurin inhibitor was given at an average of 5 days post op. Conversely, in patients who received their first dose of C.I. beyond postoperative day 8 had a rejection rate of 91% (10/11) vs. those patients receiving C.I. within eight days post transplant whose rejection rate was 29% (6/21). In the patients with renal insufficiency, the rejection rate was 35% (6/17 patients). None of these patients had steroid resistant rejection, and were easily treated with corticosteroids and increased C.I. dosing. Significant infectious complications were rare, and included 2 cases of invasive CMV, and 2 cases of early recurrent hepatitis C. Conclusions: Daclizumab used with the above dosing regimen in the absence of C.I. appears ineffective and possibly predisposes patients to steroid resistant rejection. However, it can be used safely and effectively in patients with preexisting or postoperative renal dysfunction in conjunction with low doses of C.I. given within the first week postoperatively.