Post-transplantation Lymphoproliferative Disorder in Heart and Kidney Transplant Patients: A Single-Center Experience
Authors: Wasson Sanjeev , Zafar Mohammad N. , Best John , Reddy Hanumanth K. 
Published: June 2007

Background: Post-transplantation lymphoproliferative disorder (PTLD) after heart transplantation is a fatal complication, and standard treatment is either ineffective or too toxic. We have studied the incidence, clinical course, prognostic factors, and different treatment regimens pertaining to PTLD in 110 heart and 80 kidney transplant recipients.

Methods: Information was abstracted from chart review of 110 heart transplant recipients and 80 kidney transplant recipients between January 1989 and October 2002. We report 15 patients with PTLD, 6 patients received a heart transplant and 9 patients received a renal transplant.

Results: The overall incidence of PTLD was 8.9% (5.4% in heart and 13.7% in kidney transplant recipients). The average interval between transplantation and the diagnosis of PTLD in heart transplantation patients was 5.5 years, and their overall mean age was 44 years. The indications for transplantation were ischemic cardiomyopathy in 5 patients (1 patient received both heart and kidney transplants), glomerulonephritis in 6 patients, diabetes nephropathy in 2 patients, and polycystic disease in 2 patients. Six patients were diagnosed with early disease (<12 months), 7 with late onset (1 to 10 years), and 2 with very late onset (>10 years). Five patients had PTLD grade 2 (2 heart and 3 kidney transplants) and 10 patients had PTLD grade 3 (4 heart and 6 kidney transplants). Immunosuppressive treatment for PTLD patients consisted of cyclosporine, 73% (11/15); tacrolimus, 6.6% (1/15); prednisone, 100% (15/15); azathioprine, 80% (12/15); mycophenolate mofetil, 20% (3/15); murine monoclonal anti-human CD3 (OKT3), 7% (1/15); and anti-thymocyte globulin, 13% (2/15). PTLD developed in 11.5% of patients with primary Epstein-Barr virus infection and in 28.9% of patients with primary cytomegalovirus infection. Five patients received rituximab therapy, 5 had conventional chemotherapy, 3 had radiotherapy, 3 had reduction in immunosuppression, 2 had ganciclovir, 1 underwent surgery, and 1 patient died before receiving treatment. The mortality rate was 26.6%. The average interval between transplantation and the diagnosis of PTLD in heart transplant recipients was 5.5 years. The mortality rate was significantly higher in the control group than in the rituximab group.

Conclusions: Caucasian race and male gender were independent risk factors for developing PTLD. Pretransplant cytomegalovirus seropositive status is a strong predictor of developing PTLD. Management of PTLD requires randomized controlled trials of various chemotherapeutic and antiviral drugs regimens. Treatment of PTLD with rituximab is a beneficial alternative with a favorable outcome. Patients in whom primary Epstein-Barr virus, cytomegalovirus, or hepatitis C infection develop after transplantation should be managed with heightened surveillance for the development of PTLD. Further randomized trials are needed to evaluate the efficacy of antiviral drugs, intravenous immunoglobulin, interferon, and prophylactic Epstein-Barr virus immunization strategies.