Posttransplant lymphoproliferative disorders in liver transplantation: a 20-year experience

OBJECTIVE: To evaluate the incidence of posttransplant lymphoproliferative disease (PTLD) and the risk factors and the impact of this complication on survival outcomes in a large cohort of liver transplant recipients at a single institution. SUMMARY BACKGROUND DATA: Liver transplantation has been accepted as a therapeutic option for patients with end-stage liver disease since 1983, in large part due to the availability and reliance on the use of nonspecifically directed immunosuppression. However, as predicted and subsequently verified in 1968, an increased incidence of certain de novo malignancies has been observed, particularly with regards to lymphoid neoplasms. While many reports have confirmed and clarified the nature of PTLD, the literature is fraught with conflicting experience and outcomes with PTLD. METHODS: Four thousand consecutive patients who underwent liver transplants between February 1981 and April 1998 were included in this analysis and were followed to November 2001. The effect of recipient age at the time of transplant, recipient gender, diagnosis, baseline immunosuppression, grading of PTLD, and association with Epstein-Barr virus were compared. The causes of death were also examined. Treatment for PTLD varied over the 20-year period, but all included massive reduction or elimination of baseline immunosuppression. RESULTS: The 1-year patient survival for liver transplant patients with PTLD was 85%, while the overall patient survival for the entire cohort was 53%. The actuarial 20-year survival was estimated at 45%. The overall median time to PTLD presentation was 10 months, and children had an incidence of PTLD that was threefold higher than adults. Patient survival was better in children, in patients transplanted in the era of tacrolimus immunosuppression, in patients with polymorphic PTLD, and in those with limited disease. Interestingly, neither the presence or absence of Epstein-Barr virus nor the timing of PTLD presentation appeared to influence overall patient survival. Patients transplanted for alcohol-related liver disease had a similar incidence of PTLD but had a higher risk of mortality. CONCLUSIONS: While PTLD continues to pose problems in patients receiving liver transplants, improvements in patient survival have been observed over time. While it is too early to assess the impact of new advances in prophylaxis, diagnosis, and treatment, such approaches are based on an increased knowledge of the pathophysiology of PTLD.     

Sclerosing peritonitis after intestinal transplantation in children

Long-term graft dysfunction and/or graft loss after intestinal transplantation (ITx) is a significant concern. Sclerosing peritonitis (SP) is a manifestation of chronic allograft failure and its presence may also include classic arterial obliterative arteriopathy (OA) as in chronic rejection. We describe the clinical presentation and management of SP occurring after ITx in children. Case records of 121 children undergoing ITx from 1990 to 2003 were reviewed. Three children (2.4%) presented with SP of the intestine allograft at a mean time of 6.6 yr following ITx as follows: age at Tx (yr) 8.2, and 3.7, with indication for ITx being gastroschisis in two and midgut volvulus in one patient. Type of ITx was isolated intestine in one and liver/intestine in two patients. Gross findings of SP included fibrosis/strictures; microscopically SP showed fibrosis/serositis, and fibrous adhesions; one patient had evidence of chronic allograft vasculopathy. All patients presented with clinical signs and symptoms of bowel obstruction and gastrointestinal contrast studies confirmed distal ileal obstruction (DIO). Operative findings confirmed SP and DIO in all patients; all patients were initially treated with distal segmental intestine allograft resection and lysis of the fibrous peel. All three patients recovered, although two required repeat laparotomy, there is only one long-term survival. SP after ITx may be a different manifestation of long-term intestine allograft degeneration. Surgical resection appears to offer palliation.     

De novo malignancies after intestinal and multivisceral transplantation

BACKGROUND: Maintenance immunosuppression required after organ transplantation creates a permissive environment in which cancer cells can proliferate because of lack of natural immunologic surveillance. With more than a decade of clinical experience, this report is the first to address the risk of de novo cancer after intestinal transplantation. METHODS: A total of 168 consecutive intestinal transplant recipients (86 children and 82 adults) were studied, of whom 52% were male and 91% were white. Surveillance, Epidemiology, and End Results data was used to count expected rates of de novo cancers in the general population matched for age, sex, and length of follow-up. RESULTS: With a mean follow-up of 47+/-41 months, 7 (4.2%) patients developed nonlymphoid de novo cancer, with a cumulative risk of 3% at 5 years and 28% at 10 years. Of these malignancies, one was donor-driven adenocarcinoma. With 0.58 being the expected rate of malignancy for the general population, the risk among intestinal recipients was 8.7 times higher (P =0.01). Such morbidity was significantly higher (50 times) among younger patients (<25 years), with a slight male preponderance. Induction immunosuppression was associated with early onset of de novo cancer. Patient survival after diagnosis of de novo cancer was 72% at 1 year, 57% at 2 years, and 29% at 5 years. CONCLUSION: With conventional immunosuppression, intestinal recipients are at a significantly higher risk of developing de novo cancer when compared with the general population. Thus, a novel tolerogenic immunosuppressive strategy has been recently implemented to reduce the lifelong need for immunosuppression.