Prophylactic and Pre-Emptive Therapies Using Ganciclovir and CMV Immunoglobulin Result in a Significant Reduction of CMV Disease after Intestinal Transplantation

Abstract

Introduction: CMV has plagued the field of intestinal transplantation (ITx). The combination of heavy immunosuppression in pediatric recipients of viral trophic transplanted organs has resulted in CMV disease rates reported between 10-35%. Significant graft and patient loss has also been reported. The paucity of recent data on this topic as well as the severity of the problem, prompted this retrospective review. Materials and methods: An IRB approved, retrospective review of a prospectively maintained database was undertaken at a single transplant center. All ITx recipients between 1991-2011 were included. Standard demographic data was collected. End points were survival and CMV disease defined as biopsy proven tissue invasive infection. Since 1996, a strict protocol of prophylaxis against CMV was instituted (TABLE). At the same time, a pre-emptive protocol was initiated using the results of peripheral blood monitoring for the presence of CMV DNA detected by PCR. Samples were collected every 7-30 days and pre-emptive therapy was initiated for positive results (TABLE). Surveillance endoscopy and biopsy was undertaken at predetermined intervals; tissue biopsies were also undertaken when organ dysfunction was detected clinically or on laboratory testing.Table: [Protocol]Results: 100 patients received 119 ITx. The majority were male (60%), Hispanic (54%), children (73%). Overall patient and graft survival at 1 year was 80% and 76%. High risk combinations defined by donor and recipient serologic status at the time of ITx occurred in 73%. All but the first 5 ITx received the protocol. Eight episodes (6.5%) of CMV disease occurred in 7 patients at a mean of 699 days after ITx (131-1791d). Affected tissues were native lung (n=2), native GI tract (n=3), transplanted liver (n=2), and transplanted intestine (1). No graft losses occurred due to CMV. One patient with concomitant underlying immunodeficiency disorder died directly as a result of CMV pneumonitis. CMV free survival was 99% at 1 year. Discussion: This study represents one of the few large single center reports on CMV after ITx. Using a protocol of prophylactic and preemptive therapies directed against CMV, a remarkably low rate of tissue invasive disease was seen. No tissue invasive disease was identified during the prophylactic period. In recipients without immunodeficiency, no patient or graft loss due to CMV was seen. We recommend use of such protocols to reduce CMV disease rates and improve patient and graft survival after ITx.