The Effect of Tacrolimus on Time to Development of Post-Transplant Lymphoproliferative Disorder (PTLD).

Post Transplant Lymphoproliferative Disorder (PTLD) is a rare but potentially fatal complication occurring after solid organ transplant. PTLD is divided pathologically into three subgroups: early lesions, polymorphic PTLD, and monomorphic PTLD. The severity of these complications ranges from reactive lymphoid hyperplasia to aggressive non-Hodgkin lymphoma and Hodgkin-like lymphoma. Most PTLD are of B cell lineage associated with infection or reactivation of Epstein Barr virus (EBV). Post-transplant patients on immunosuppressive therapy may lack sufficient cytotoxic T cells to clear EBV-infected B cells, allowing unchecked polyclonal B cell proliferation and infection of other cells with EBV. Immunosuppression with cyclosporine and tacrolimus has been associated with a higher risk for development of PTLD. This study examines the relationship between tacrolimus and PTLD among solid-organ transplant patients.

Differences in time to PTLD between patients with and without exposure to tacrolimus were assessed using a retrospective, case-control design. University of Virginia Health System registry records were searched to identify all patients in the post- solid organ transplant population diagnosed with malignancy in the years 1998–2009. Bone marrow transplant patients were excluded. Following IRB approval, data was collected on the type of transplant, immunosuppressive regimen, time from transplant to development of PTLD, and lymphoma treatment; from electronic charts and pathology reports were reviewed.

A total of 2841 patients with solid organ transplants were identified, including1486 patients who received tacrolimus for immunosuppression. There were 26 cases of PTLD: 19 with exposure to tacrolimus (1.3%), and 8 without exposure (0.6%). The mean time to PTLD was 2.52 years (SD = 0.65) in the tacrolimus group, and was 6.75 years (SD = 1.80) among those not exposed. This difference in time to event was stat istically significant (Log-Rank = 5.347, p = .0208).

In our population of post solid organ transplant patients with PTLD, exposure to tacrolimus was associated with significantly shorter time to development. Prospective studies are needed to better elucidate the relationship between type of immunosuppression and development of PTLD. These results suggest that immunosuppressive regimens using tacrolimus may be associated with increased risk of developing PTLD.

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No relevant conflicts of interest to declare.