Posttransplant Lymphoproliferative Disorder in Liver Transplant Recipients: A Report of Seventeen Cases.

Posttransplant lymphoproliferative disorder (PTLD) is a major complication of liver transplantation. The optimal approach to these patients remains to be determined. We report a retrospective analysis of seventeen consecutive cases of PTLD seen at the University of Pennsylvania Medical Center. A total of 1179 liver transplants have been performed, of which 15 (1.3%) patients developed PTLD. There were two additional patients in this series that received their transplant elsewhere. The most common indications for liver transplantation were viral hepatitis (35%) and/or alcoholic cirrhosis (29%). Of the seventeen PTLD patients identified, most were Caucasian (76%) and/or male (76%). The median age at PTLD diagnosis was 50 yrs (range 20–65 yrs) with a median time from liver transplantation to PTLD diagnosis of 25 months (range 3–75 months). The most common presenting symptoms included fevers (47%), weight loss (47%), anorexia (47%), and pain (70%). PTLD location was frequently extranodal (71%) and/or involved the transplanted liver (41%). At diagnosis, immunosuppressive medications included OKT3 (12%), steroids (71%), azathioprine (41%) or mycophenolate mofetil (12%), and cyclosporine (65%) or tacrolimus (35%). PTLD histology consisted of 9 (53%) monomorphic and 8 (47%) polymorphic. EBV was detected by in situ hybridization in 11 (79%) of 14 cases evaluated. Stage at diagnosis was I (29%), II (35%), III (12%), and IV (12%). Initial therapy included reduction in immunosuppression (RI) alone in 13 (76%) of 17 patients. The remaining 4 patients were treated with retransplantation, rituximab + RI, alpha interferon, or chemotherapy. RI alone resulted in 6 (46%) CR and 7 (54%) PD. The addition of rituximab to RI in 1 patient resulted in an additional CR. R±CHOP was used as initial therapy in one patient and in 2 patients as salvage after relapse with all attaining a CR. Current median follow-up is 6 months (range 7 days to 9 years) with PFS of 6 months. Median overall survival following PTLD diagnosis was 6 months (range 7 days to 9 years). Of the 12 expired patients, 6 (50%) died from progressive PTLD, 3 (25%) from liver failure, 2 (17%) from infection, and 1 (8%) from cardiomyopathy. Currently, 5 patients are alive in CR (follow-up times of 6 months, 3.5 yrs, 4.5 yrs, 6 yrs and 8.5 yrs). Although the detection and treatment of PTLD in liver transplant recipients remains problematic and the upfront mortality is still high, long-term survival is possible. Further studies are necessary to better define treatment strategies.