Epstein-Barr Viral Load in Post Renal Transplant Lymphoproliferative Disease: Elevated EBV DNA Levels at Diagnosis and Clearence after Rituximab Therapy.

The imbalance between EBV load and host immunological status is the trigger for post transplant lymphoproliferative disease (PTLD) development. Thus, monitorization of EBV load can be a useful tool in the management of these patients. In order to evaluate this issue in a renal transplant center, we studied eleven PTLD cases between January 2001 and December 2003. The diagnosis of PTLD was established according to WHO classification and confirmed by in situ hybridization (ISH) for EBV. Real-time PCR (LightCycler System, Roche, USA) and primers for amplification of EBV’s EBNA-1 gene were used to evaluate EBV viral load in peripheral mononuclear cells (PBMC) of PTLD cases. Samples were collected at diagnosis and 1, 3, 6 and 9 months after therapy. Median time from renal transplant to PTLD onset was 36 months. Eight (73%) were classified as diffuse large B-cell lymphoma, one as lymphoplasmocytoid lymphoma, one as polymorphic hiperplasia and one as Hodgkin’s lymphoma. All PTLD cases presented positive IgG and negative IgM antibodies, indicating remote EBV infection. All patients had their immunosuppression reduced (n=11), 5 received chemotherapy and 6 received monotherapy with Rituximab. Six patients (54%) achieved complete remission (CR), interestingly those with IPI <=2, with a median follow-up of 20.5 months. Six (54%) patients died (four of PTLD and two of sepsis). At diagnosis, median EBV viral load of PTLD cases was 17,400 copies/106 PBMC (range 1,000 to 227,590). All six patients who achieved CR cleared their viral load one month after therapy initiation, independent of EBV levels at diagnosis and kept it undetectable during follow-up. Five out of six patients who received Rituximab achieved CR. We conclude that clearance of EBV load occurs early after therapy start and that its maintenance probably depends on restoration of T-cell defense after immunosuppression reduction. We also concluded that Rituximab monotherapy may be a reasonable therapy with a low toxicity profile in this group of patients.